A. Kapila and A. Kapila
Stephen Barrett, Alastair Proudfoot, and Luigi Camporota
Simon Finney and Mark Griffiths
Anthony Bastin and Mark Griffiths
John Park and Mark Griffiths
James Hull and Julian Lentaigne
Clare Ross and Julian Lentaigne
Karthi Srikanthan, Felix Chua, and Pallav L. Shah
Jonathan M. Handy, Kate C. Tatham, and Emma Fitzgerald
Wissam Abouzgheib and R. Phillip Dellinger
Thiago Lisboa and Jordi Rello
There are few medical conditions that are as rapidly and predictably lethal as the loss of upper airway patency. Because of the relative infrequency with which upper airway obstruction (UAO) is encountered by most physicians, opportunities to acquire significant clinical experience are limited. This, combined with the frequently subtle presentation of UAO and the clinician’s inability to visualize the upper airway in its entire extent through routine physical examination, may hamper diagnosis of this condition until a crisis results.
The sites of UAO may be within the airway lumen, in the walls, or extrinsic to the airway. Further, sites of UAO can be divided into supraglottic, glottic, and infraglottic above the carina. Finally, UAO will behave differently during inspiration and expiration if intrathoracic or extrathoracic.The intrathoracic airway dilates during inspiration as it is exposed to the expansive force of negative intrapleural pressure. Positive intrapleural pressure during expiration causes compression and narrowing. The compliant extrathoracic airway, not exposed to intrapleural pressure, collapses during inspiration and increases in diameter during expiration. UAO is likely to occur at sites of anatomic narrowing such as the hypopharynx at the base of the tongue and the false and true vocal cords at the laryngeal opening.
See Box 18.1 for functional causes.
Clinical presentation and initial evaluation
Rapidly progressing series of events. Patient is unable to breathe, speak, or cough and may hold the throat between the thumb and index finger (the universal choking sign). Anxious and agitated. Vigorous attempts at respiration with intercostal and supraclavicular retraction. Heart rate and blood pressure raised. Patient becomes rapidly cyanosed.
Respiratory efforts diminish, loss of consciousness, bradycardia, and hypotension. Cardiac arrest.
Death is inevitable if the obstruction is not relieved within 2–5 min of the onset.
Stable, or progressive deterioration.
Signs and symptoms may be mild but, as they worsen, include coughing, inspiratory stridor, crowing or noisy respiration, dysphonia, aphonia, choking, drooling, and gagging. Dyspnoea, feeble cough, respiratory distress and signs of hypoxaemia and hypercarbia such as anxiety, confusion, lethargy, and cyanosis may be present as the obstruction worsens.
Powerful inspiratory efforts against an obstruction may produce dermal petechiae and subcutaneous emphysema or, in acute fulminant negative pressure, pulmonary oedema. Partial airway obstruction that is worsening should be aggressively managed and, if rapidly progressing, immediate preparation for treatment as complete obstruction should be made.
In stable, non-progressing cases of partial obstruction specific diagnostic evaluation may be undertaken provided the patient is strictly observed for any signs of deterioration and facilities for skilled airway management are immediately available.
Laryngoscopy and bronchoscopy
Laryngoscopy using flexible nasoendoscopy in a stable, cooperative patient is useful in diagnosing foreign bodies, retropharyngeal or laryngeal masses, and other glottic pathology. In skilled hands it is quick, simple, and atraumatic.
If laryngoscopy is conducted using a flexible intubating laryngoscope or bronchoscope, definitive airway control can be achieved at conclusion of examination by railroading an endotracheal tube into the trachea. Disadvantages are need for a skilled operator, time to achieve local anaesthetic topicalization of the airway, and a cooperative patient. It can be very difficult in the presence of blood and secretions. A traumatic procedure will lead to worsening swelling, bleeding, and oedema, and potential catastrophic loss of the airway.
If time allows, anteroposterior and lateral plain neck radiographs can be useful in detecting radio-opaque foreign bodies, retropharyngeal masses, and epiglottitis. The lateral view should be obtained during inspiration with the neck fully extended.
Computed tomography (CT) scanning in stable patients enables assessment of the integrity of the thyroid, cricoid, and arytenoid cartilages as well as the status of the airway lumen.
A myriad of techniques using a huge variety of equipment has been described for management of UAO. The key principles are to have agreed a set number of techniques and to provide training and equipment for these for each institution.
Reverse hypoxia with 100% oxygen. Gain intravenous access as soon as practicable. Continuous monitoring and observation with the most skilled personnel available. Assess the airway carefully to delineate where and what type of UAO is present. Plan the approach to airway management with plan A and subsequent back-up plans in the event of failure.
Airway equipment should be readily available, ideally on a movable trolley with an agreed contents list that is maintained regularly. Such a list would include a choice of laryngoscopes, blades, and endotracheal tubes (ETT), fibreoptic bronchoscope or laryngoscope, bougies, a choice of supraglottic airway devices such as laryngeal mask airways (LMA™) and intubating laryngeal mask airways (ILMA™), and equipment necessary for a surgical airway (cricothyroidotomy set, tracheostomy tray, and equipment for transtracheal jet ventilation), emergency drugs, and good suction.
Principles of airway management techniques
Try simple manoeuvres to open airway, jaw thrust, or insertion of an oropharyngeal or nasopharyngeal airway may be effective in the unconscious or obtunded patient.
Consider the coma position to maintain the airway if the cervical spine is clear.
If UAO persists the key principle in gaining formal airway control is not to lose oxygenation during the intubation attempts. Supraglottic airway devices such as the LMA and ILMA can provide a means of oxygenation and a conduit for endotracheal intubation.
If a full stomach is likely and a rapid sequence intubation indicated then careful head and neck positioning and cricoid pressure with the BURP manoeuvre (backward, upward, and rightward pressure) may improve laryngeal visualization. Preloading the ETT onto a bougie will minimize apnoeic time. Use of a CO2 detector (capnography or single-use device) will ensure correct placement of the ETT in the trachea.
If appropriate skills are available then flexible endoscopic techniques may be considered. This can be achieved through an LMA, for example, or under local anaesthesia if time permits. Siting of a cricothyroid cannula beforehand can provide oxygenation using transtracheal jet ventilation during the intubation attempt and can remove the sense of extreme urgency from the situation. Care with allowing time for exhalation and not overinflating the lungs will avoid barotrauma, especially in the presence of severe UAO.
In the presence of blood and excessive secretions, flexible endoscopic techniques may be impossible. Retrograde tracheal intubation over a J-tip guidewire passed cranially via the cricothyroid membrane can be useful in this scenario.
A surgical airway is indicated when earlier airway plans have failed or at the outset if endotracheal intubation is not possible (e.g. bleeding into oral surgery microvascular flap with severe UAO) or if an unstable cervical spine is threatened by available airway techniques. The key principle here is to recognize the need for a surgical airway early and not wait until the patient is already severely hypoxic.
Percutaneous transtracheal jet ventilation using one of the proprietary needle cannula/catheters/jet ventilation systems (e.g. VBM Manujet™) inserted through the cricothyroid membrane can be achieved relatively quickly.
Cricothyrotomy with a wide-bore cannula or even an ETT with a minimum internal diameter of 5 mm will allow adequate gas exchange through a normal breathing circuit. The cricothyroid space is 9 × 30 mm in an adult, therefore up to a size 8.5-mm outer diameter tube should avoid complications such as laryngeal fracture and vocal cord damage. Complications such as subglottic stenosis, thyroid fracture, haemorrhage, and pneumothorax are uncommon.
Emergency tracheostomy is rarely required. Formal surgical tracheostomy under local anaesthesia may be a prudent approach under some controlled conditions.
Respiratory failure is a condition in which the respiratory system is unable to maintain adequate gas exchange to satisfy metabolic demands, i.e. oxygenation and/or elimination of CO2 from mixed venous blood. The respiratory system consists of a gas-exchanging organ (the lungs) and a ventilatory mechanism (respiratory muscles/thorax), either or both of which can fail and precipitate respiratory failure.
Respiratory failure is generally classified into:
• Hypoxaemic (type I). This is the most common form of respiratory failure and is invariably associated with parenchymal lung diseases (Table 18.1). It is characterized by an arterial partial pressure of oxygen (PaO2) <8.0 kPa (60 mmHg) with a normal or low partial pressure of carbon dioxide (pCO2).
• Ventilatory (type II). This is secondary to failure of the ventilatory pump, and characterized by hypoventilation with hypoxia and hypercapnia (arterial partial pressure of carbon dioxide [PaCO2] >6.5 kPa), which, in the absence of supplemental oxygen, is invariably associated with hypoxaemia (Table 18.1).
Table 18.1 Common causes of respiratory failure
Type I: hypoxaemic
Type II: hypercapnic
Chronic obstructive pulmonary disease (COPD)
Acute respiratory distress syndrome
Drug overdose (opiates)
Central nervous system insult (trauma, cerebrovascular accident)
Primary muscle disorders
Obesity hypoventilation syndrome
Hypoxaemic—type I (PaO2 <8 kPa)
Type I respiratory failure derives from one or more of the following four pathophysiological mechanisms: ventilation/perfusion mismatch, true shunt, diffusion impairment, or reduced inspired oxygen concentration.
Ventilation/perfusion (V/Q) mismatching occurs when alveolar units are poorly ventilated in relation to their perfusion (V/Q <1). As the degree of V/Q mismatch increases, hypoxaemia worsens because a greater proportion of the cardiac output will be inadequately oxygenated. This effect is amplified owing to the sigmoid shape of the haemoglobin dissociation curve; high or normal V/Q alveolar units cannot compensate for the units at low V/Q ratio.
True shunt (V/0) occurs when deoxygenated mixed venous blood completely bypasses ventilated alveoli, resulting in ‘venous admixture’. This occurs in health and is normally 1–5% of the cardiac output owing to drainage from the bronchial veins (lung) and the Thebesian veins (heart).
Shunt fraction (Qs/Qt, where Qs is shunted bloodflow and Qt is total bloodflow) is the quantity of blood that would be required to reduce the saturation of the pulmonary end-capillary blood to the observed value of PaO2 and can be calculated as:
Or, more simply, as:
Where CcO2 = capillary oxygen content, CaO2 = arterial oxygen content, CvO2 = venous oxygen content, SaO2 = arterial oxygen saturation, and SvO2 = mixed venous oxygen saturation.
In practice, it is difficult to distinguish between true shunt and V/Q mismatch, and they often occur simultaneously. V/Q mismatch results in hypoxaemia because the distribution of alveolar oxygen tension is uneven. When breathing fractional inspired oxygen concentration (FiO2) 1.0, the PaO2 becomes uniform with V/Q mismatch and may lead to an improvement in PaO2. However, in true shunt an increase in PaO2 does not solve the absence of a diffusible pathway, therefore in true shunt, the PaO2 will not be improved by high-flow oxygen.
Diffusion impairment occurs when the movement of oxygen from the alveolus to the pulmonary capillary is impaired and there is insufficient time for oxygenation to occur. This is in accordance with Fick’s Law and is affected by thickness, surface area, pressure differences, and a diffusion constant. This is invariably related to extensive and/or destructive lung disease, where V/Q mismatch is also a significant factor, and in its pure form occurs rarely in clinical practice.
Reduced inspired oxygen concentration is generally not a clinical problem outside extreme environments such as altitude or deep sea diving and can be overcome by increasing the FiO2. It may occur in healthcare due to machine, cylinder, or delivery device error. For this reason, modern ventilators are all required to have a hypoxic guard or oxygen analyser to avoid the administration of a hypoxic gas mixture. Nonetheless, device error should always be borne in mind, particularly after equipment changes.
Initially, the hypoxaemia present in type I respiratory failure is frequently associated with a compensatory increase in minute ventilation and therefore decreased PaCO2. However, as the condition persists or progresses, fatigue of the respiratory muscles or central nervous system (CNS) impairment may lead to an increase in PaCO2.
Another factor that may contribute to hypoxaemia is low mixed venous oxygen saturation (SvO2). Normally, only 20–30% of the delivered oxygen is extracted by the tissues and the resulting venous oxygen levels can be measured using a central venous catheter (central venous oxygen saturation, ScvO2) or in the pulmonary artery using a pulmonary artery catheter (SvO2). SvO2 values of ~65–75% represent an optimal balance between global oxygen supply and demand. The lower the SvO2 the greater will be the effect of shunt or low Va/Q ratio on PaO2; this can be optimized by increasing cardiac output using volume resuscitation or inotropy.
Hypercapnic—type II (PaO2 <8 kPa and PaCO2 >8 kPa)
In normal conditions PaCO2 is maintained within strict limits (4.8–5.9 kPa). Hypercapnic respiratory failure may occur either in acute, chronic, or acute-on-chronic phases. The common denominator in type II respiratory failure is reduced effective alveolar ventilation (VA) for a given CO2 production (VCO2).
The relationship between end-tidal CO2 and VCO2 is:
End-tidal concentration in % approximates to end-tidal value in kPa. Partial pressure can be substituted and there is a close but unpredictable relationship between PaCO2 and end-tidal CO2, so the equation can be rewritten
Where VE is minute ventilation and VD is dead space ventilation, VT is tidal volume and f is respiratory frequency. Under conditions where VCO2 remains unchanged, the resulting pCO2 will depend on the interaction between respiratory rate, tidal volume, and the degree of dead space ventilation. Although the latter is often assumed to be fixed, in reality the physiological dead space may vary within a given patient and depends on the interaction between alveolar and pulmonary vascular pressures, including inadequate or excessive positive end-expiratory pressure (PEEP). This can be particularly important in critically ill patients where cardiovascular status interacts with the need for positive pressure ventilation. VCO2 is rarely the limiting factor in normal lungs, but even normal (carbohydrate-based feeds) or slightly increased (increased work of breathing) VCO2 may be a problem with extensive lung disease.
Clinically, type II (hypercapnic) respiratory failure occurs under four circumstances.
• Central CNS depression with reduction of the respiratory drive (e.g. drugs, CNS diseases).
• Impaired respiratory muscle function (e.g. neuromuscular diseases, malnutrition, drugs, skeletal deformities, respiratory muscle dysfunction, or fatigue from excessive mechanical load).
• V/Q mismatch (high V/Q, with increase in dead space ventilation).
• Increased CO2production in extreme cases (malignant hyperthermia) can be the sole cause.
Acute versus chronic respiratory failure
Acute type II respiratory failure develops over minutes to hours and is invariably associated with an acidosis (pH <7.35). In chronic type II respiratory failure, hypercapnia develops over a much longer period, allowing time for renal compensation with an increase in bicarbonate concentration and minimal change in pH. The distinction between acute and chronic hypoxaemic (type I) respiratory failure may not always be easily made on the basis of arterial blood gases, but clinical markers of chronic hypoxaemia, including polycythaemia and cor pulmonale, suggest longstanding pathophysiology.
The assessment of a patient with suspected respiratory failure requires a thorough clinical history and examination in conjunction with specific investigations. The degree to which this is feasible may depend on the severity and rapidity with which the patient is deteriorating and often information will become apparent retrospectively. Nonetheless, a full history and examination should be completed as soon as is practicable, and clinical observation should be repeated at regular intervals to assess clinical improvement.
• Arterial blood gas analysis, with repeated sampling and trends.
• Electrocardiograph (ECG).
• Chest X-ray (CXR).
• Venous bloods: full blood count (FBC), urea and electrolytes (U+Es), liver function tests (LFTs), C-reactive protein (CRP).
• Septic screen (culture blood, sputum, urine).
P(A–a)O2gradient: the alveolar to arterial (A–a) oxygen gradient is calculated by subtracting the PaO2 from the alveolar PAO2, calculated using the alveolar gas equation:
Where PIO2 is the partial pressure of inspired oxygen and R is the respiratory quotient, assumed to be 0.8. The normal A–a gradient (2–4 kPa) varies with age and FiO2. Hypoventilation can be differentiated from other causes of hypoxaemia by the presence of a normal A–a gradient.
P(A-a)/PaO2ratio or respiratory index: this is calculated by dividing the P(A–a)O2 gradient by PaO2. Unlike the P(A–a)O2 gradient it is relatively unaffected by the FiO2. The normal P(a/A)O2 ratio varies from 0.74–0.77 when FiO2 is 0.21, to 0.80–0.82 when FiO2 is 1.
PaO2/FiO2ratio: the most widely used index, being easy to calculate and a good estimate of shunt fraction. Reflective of this, it has been incorporated into the Berlin definition of acute respiratory distress syndrome (ARDS), with ratios of ≤39.9 kPa, ≤26.6 kPa, and ≤13.3 kPa reflecting mild, moderate, and severe ARDS, respectively.
Principles of treatment
Respiratory failure is managed by a combination of specific and supportive measures. General principles may include the following:
• Ensure a patent airway and administer oxygen to maintain SaO2>90%.
• Correct reversible and treatable causes (e.g. drain pleural effusion or pneumothorax), including physiotherapy to mobilize secretions.
• Early non-invasive ventilatory support (continuous positive airway pressure [CPAP]/bilevel) to improve oxygenation, reduce work, and reduce hypercapnea.
• Invasive mechanical ventilator support in those who fail non-invasive ventilation or have a contraindication to facemask ventilation.
• Optimize cardiac output and oxygen delivery through a combination of fluids, red cell transfusion, and inotropes.
The terms atelectasis and collapse are often used interchangeably. Pulmonary collapse can affect any anatomical division of the lung, i.e. the whole lung, a single lobe, or segments or subsegments of a lobe. It occurs because of a reduction or complete cessation of ventilation.
Obstructive (resorptive) atelectasis
Intrinsic obstruction of the airway with distal resorption of air obstruction: inhaled foreign body, aspiration, neoplasms, mucus plugs, asthma, bronchiectasis, allergic bronchopulmonary aspergillosis, secretions (pneumonia), and endobronchial intubation. This may also occur with ‘excessive’ oxygen administration whereby oxygen (which is more soluble than nitrogen) diffuses quickly into the pulmonary vasculature, so quickly in fact that an inadequate volume of gas remains in the alveolus, predisposing it to collapse.
Relaxative (passive) atelectasis
Interruption of the negative pressure holding visceral and parietal pleura in close contact causes the lung to retract: pneumothorax and pleural effusions.
External compression of the lung by chest wall, pleural, or mediastinal structures. This can be localized or regional in nature: neoplasms (primary or secondary), lymphadenopathy (e.g. sarcoid, tuberculosis [TB], lymphoma), cardiomegaly (especially affecting left and middle lobe bronchus), loculated pleural collections, abdominal distension (ascites, ileus, abdominal compartment syndrome), obesity, neuromuscular weakness, chest pain (e.g. postsurgical, trauma).
Increased surface tension within the alveoli owing to decreased production or inactivation of surfactant: ARDS, infant respiratory distress syndrome (IRDS), pulmonary oedema, near drowning.
Loss of lung volume because of parenchymal scarring: granulomatous disease, radiation, necrotizing pneumonia.
• V/Q mismatching (shunt).
• Reduced functional residual capacity (FRC).
• Increased work of breathing.
• Surfactant dysfunction in collapsed region.
• Decreased thoracoabdominal compliance (passive and compressive atelectasis).
• Increased risk of infection (distinct from ‘simple’ atelectasis without infection).
• Increased bacterial growth in collapsed region (stagnation).
• Development of respiratory failure.
The severity of the changes seen depends on the degree and rapidity of the developing collapse.
Pulmonary collapse is common, the exact frequency depending on the cause. In patients who have undergone open abdominal surgery the incidence of significant subsegmental collapse approaches 20–25%. It is estimated that in all patients undergoing non-cardiothoracic surgery, the frequency of postoperative pulmonary complications is 5–10%.
Presenting features will depend on speed of onset, cause, and severity of the atelectasis. Many patients may be asymptomatic, but common symptoms include breathlessness, cough, and chest pain; some may report systemic features. A full history and examination may help to identify the aetiology.
• Fever, tachycardia.
• Cyanosis (if severely hypoxaemic).
• Low SaO2.
• Reduced chest expansion on the affected side.
• Trachea deviated towards the side of the collapse*.
• Dull percussion note over affected area*.
• Reduced breath sounds over affected area*.
• Other signs that the patient is at risk of pulmonary collapse, e.g. chest and abdominal wounds, abdominal distension, neuromuscular abnormalities.
(*Only if significant volume of the lung is affected.)
It is often difficult clinically to differentiate collapse from consolidation or pleural fluid; frequently these entities will coexist (Table 18.2).
Table 18.2 Radiographic differences between collapse, consolidation and pleural fluid
Away from lesion
Away from lesion
• CXR: ideally a PA film, but a lateral may be useful.
• Markers of infection and inflammation (FBC, CRP, sputum and blood cultures) as indicated.
• Arterial blood gases (ABGs) to assess the degree of gas exchange abnormalities (hypoxaemia, hypercarbia/hypocarbia).
• Chest ultrasound may differentiate collapsed lung from a pleural effusion.
• Bronchoscopy: both diagnostic (large airway obstruction, e.g. foreign body, sputum plug, tumour) and therapeutic (with or without lavage).
• CT may demonstrate the anatomy and may define causes, e.g. endobronchial lesion, lymphadenopathy.
• Displacement of intralobular fissures.
• Loss of aeration within the visible lung fields.
• Vascular and bronchial ‘crowding’.
• Elevation of hemidiaphragm.
• Mediastinal displacement.
• Hilar displacement.
• Compensatory hyperinflation of remaining lung.
• ‘Crowding’ of ribs.
Lobar collapse is associated with well-defined patterns on the chest radiograph. However, CXR signs can be subtle and easily overlooked by the unwary clinician. Total lung collapse results in complete opacification of the affected hemithorax, with indicators of marked volume loss on that side, mediastinal shift, and hyperinflation of the contralateral lung. Subsegmental (plate, discoid) atelectasis may appear as peripheral band-like densities perpendicular to the pleural surface.
Stabilize the patient
• Assess ‘airway, breathing and circulation’.
• Apply oxygen, establish vascular access, commence ECG monitoring.
• Assess the need for ventilatory support (non-invasive or invasive).
Identify causes and treat
It is important to identify the likely causes of collapse as some are amenable to specific therapeutic interventions.
Intrinsic airway obstruction:
• Bronchoscopy to remove the source of obstruction.
• Endobronchial stenting for a neoplastic lesion.
Removing external sources of compression:
• Drain pleural effusion.
• Treat pneumothorax (needle decompression and/or tube thoracostomy).
• Drain large volume ascitic fluid.
Re-expansion (re-recrutiment) of collapsed lung:
• CPAP (non-invasive ventilation).
• Invasive mechanical ventilation with PEEP (to minimize alveolar collapse during expiration).
Specific management options
There is little evidence for the prophylactic use of physiotherapy for the prevention of atelectasis. However, there is evidence for its efficacy in treatment, including manual treatments (percussion, vibration, and positive pressure assist devices) in conjunction with patient positioning and incentive spirometry.
Aside from its diagnostic use, bronchoscopy can be used for therapeutic intervention, e.g. to remove a foreign body or, more commonly, remove retained secretions. It is commonly applied in the intensive care unit (ICU), achieving similar results to physiotherapy. Case series demonstrate an improvement in PaO2, lung compliance, and CXR findings. It can be considered in lobar and segmental rather than subsegmental collapse, but may be less effective in patients who demonstrate air bronchograms on the preceding chest film.
Mucolytics (N-acetylcysteine, DNase)
Such therapies aim to reduce the viscosity of secretions, making them easier to clear and reducing mucus plugging. Although DNase has been shown to be effective in cystic fibrosis, definitive evidence in other conditions is scarce and decisions regarding its use should be made on a case-by-case basis.
The following manoeuvres can be considered in isolation or in concert to re-expand collapsed regions/prevent regional (dependent) lung collapse.
• Higher levels of PEEP/CPAP.
• Recruitment manoeuvres: transient application of high levels of PEEP (30–40 cmH2O) for short periods of time (beware patients at risk of hypotension and/or barotrauma).
• Positioning the patient with collapsed segments in non-dependent position (consider lateral or even prone position if severely hypoxaemic).
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow obstruction that is not fully reversible. The airflow obstruction does not significantly alter over several months and is usually progressive in the long term. The airflow obstruction is caused by a combination of airway and parenchymal damage. COPD is predominantly caused by smoking. Other factors, including genetic causes, such as α1-antitrypsin deficiency, occupational and environmental exposures, and, in particular, in developing countries, exposure to biomass fuels, may also contribute to the development of COPD. COPD is currently the third leading cause of death globally.
Airflow obstruction is defined as an FEV1/FVC ratio of <0.7 (where FEV1 is forced expiratory volume in 1 s and FVC is forced vital capacity), usually in combination with an FEV1 of <80% predicted. However, a diagnosis of mild COPD can be made in those with an FEV1 >80% in the presence of symptoms such as breathlessness and cough. There is no single diagnostic test for COPD; rather it is based on a combination of clinical judgement with an appropriate history and examination in combination with postbronchodilator obstructive spirometry.
Severity (GOLD stage) defined on the basis of FEV1 is shown in Table 18.3.
Table 18.3 Severity (GOLD stage) defined on the basis of FEV1
FEV1 >80% predicted
FEV1 50–79% predicted
FEV1 30–49% predicted
FEV1 <30% predicted
Differential diagnosis includes asthma, bronchiectasis, cardiac failure, lung cancer, and bronchiolitis. These conditions may also coexist with COPD.
Investigations include CXR, pulse oximetry, and postbronchodilator spirometry plus where indicated to exclude differential measurement of acute bronchodilator reversibility, full lung function testing, peak flow diary, FBC, ABGs, ECG, echocardiogram, sputum culture, α1-antitrypsin level, and thoracic CT scan.
Management of stable COPD
Most treatments for stable COPD aim at controlling symptoms, reducing exacerbations, and maintaining or improving exercise capacity and quality of life. Of all treatments available, only long-term oxygen therapy (LTOT) in hypoxaemic patients has been shown to reduce mortality. Smoking cessation reduces the rate of decline of lung function, whilst lung transplantation and intervention through lung volume reduction surgery or endobronchial valves and coils can result in improved lung function. Combination inhaled therapy has been shown in several large multicentre trials to reduce exacerbation frequency and reduce the annual decline in FEV1.
Current management of stable COPD includes:
• Inhaled bronchodilators:
○ First line in mild–moderate COPD: short-acting β2-agonists and anticholinergics.
○ Next step: long-acting muscarinic antagonists (LAMAs) and/or long-acting β2-agonists (LABAs).
• High-dose inhaled corticosteroids to prevent exacerbations, only in severe COPD (FEV1 <50% and persistent symptoms/recurrent exacerbations).
• Oral modified release theophyllines.
• Oral mucolytics in patients with productive cough or at times of exacerbation.
• Phosphodiesterase 4 inhibitors: for use in severe COPD to reduce airway inflammation and reduce exacerbations—little used due to side-effects.
• Diuretics for oedema due to cor pulmonale.
• Antibiotics; used in exacerbations. Use of azithromycin at low dose for maintenance (anti-inflammatory effects) in those with frequent exacerbations—concerns re building antibiotic resistance.
• Oxygen: LTOT for patients with PaO2 <7.3 kPa (or <8.0 kPa plus polycythaemia or cor pulmonale). Ambulatory oxygen for patients already on LTOT where desaturation occurs on exercise and in whom exercise capacity and/or symptoms improve when oxygen is administered.
• Pulmonary rehabilitation: multidisciplinary programme comprising physical training and disease education suitable for all patients in whom dyspnoea limits activity.
• Smoking cessation: nicotine replacement therapy, bupropion, or varenicline combined with an appropriate support programme. Increasing use of e-cigarettes not yet formally recommended as a smoking cessation adjunct owing to lack of evidence and knowledge re potential side-effects and long-term effects.
• Pneumococcal and annual influenza vaccination.
• Dietetic advice for patients with abnormal body mass index (BMI).
• Nocturnal non-invasive ventilation (NIV) may be of value in patients with chronic hypercapnic ventilatory failure with nocturnal hypoventilation and repeated admissions.
• Endobronchial valves: inserted via bronchoscopy to achieve atelectasis of selected lung segments and thereby volume reduction. Patients need to meet lung function criteria (total lung capacity [TLC] >150%, residual volume >200%, as well as severe obstructive airways parameters) and have heterogeneous emphysema on CT. Need assessment and exclusion of collateral ventilation preprocedure. Multicentre randomized trials have shown improvements in FEV1 and health status following valve insertion. Main risks are pneumothorax and infection.
• Endobronchial coils—still mostly in trials currently—nitinol devices implanted into the lung endobronchially to achieve volume reduction—can be used where collateral ventilation occurs and in homogeneous emphysema. Trials to date show small improvements in lung function and quality of life.
• Lung volume reduction surgery: consider in patients with upper lobe-predominant emphysema where symptoms persist despite maximal medical therapy. Lung function parameters should be at least 20% predicted and PaCO2 <7.3 kPa. Decreasing use due to higher morbidity and mortality compared to endobronchial techniques now available.
• Lung transplantation: single or double lung if FEV1 is <25% predicted and/or cor pulmonale present plus severe symptoms despite maximal medical therapy. Recipients must be non-smokers and <65 years old.
Acute exacerbations of COPD
Exacerbations often occur in COPD, described as a rapid and sustained worsening of symptoms beyond normal day-to-day variations, leading to a change in medication. Typically patients present with increased dyspnoea, cough or wheeze, chest tightness, increase in sputum volume, and/or purulence. Exacerbations of COPD are a major cause of morbidity and mortality, accounting for 1 in 8 of acute medical admissions.
Commonly infective (viral and bacterial), but others include air pollution (nitrogen and sulfur dioxide, ozone and particulates, and biomass fuels. In some cases the cause is unidentifiable. The most common bacterial pathogens are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Viral causes include rhinovirus, influenza, coronavirus, and adenovirus.
Pneumonia, pulmonary oedema, PE, pneumothorax, pleural effusion, lung cancer, UAO, and recurrent aspiration.
CXR, ECG, ABGs, FBC, U&Es, CRP plus blood cultures if pyrexial, and theophylline level if the patient is on oral theophylline therapy. Sputum microscopy culture and sensitivity if purulent.
Signs of a severe exacerbation include severe dyspnoea/tachypnoea, use of accessory muscles and pursed lip breathing, acute confusion, reduced Glasgow Coma Score, new peripheral oedema, new cyanosis, and respiratory acidosis on ABGs. Mortality rises sharply in patients with a pH of <7.25. If none of the above is present, the patient may be suitable for home management of their exacerbation dependent upon other comorbidities and social circumstances.
Aim to maintain adequate levels of oxygenation without precipitating worsening hypercapnia and acidosis. Ideally, SaO2 should be between 88 and 92%; in those without type 2 respiratory failure, a higher target saturation range of >94% may be used. Oxygen should be delivered via facemasks that allow accurate determination of FiO2. SpO2 should be monitored and ABGs repeated in those with hypercapnia to monitor response to treatment.
Hypoxaemia may recover slowly following an acute exacerbation of COPD (AECOPD), after other symptoms have improved. This only requires treatment if the patient is symptomatic. For oxygen to be supplied to a patient’s home, a Home Oxygen Order Form needs to be completed. In these circumstances, the respiratory team should be contacted so that an assessment for LTOT can be arranged ~6 weeks later.
Salbutamol 2–4-hourly plus as required and ipratropium 6-hourly should be prescribed until the patient has stabilized and can use inhalers. Nebulizers should be driven with compressed air in patients with hypercapnia and/or respiratory acidosis, with supplemental oxygen being delivered via nasal cannulae if required.
All patients should be prescribed oral prednisolone 30 mg/day for 1–2 weeks. IV hydrocortisone should only be used in patients who are unable to take enteral medication. There is no proven benefit in continuing steroids beyond 14 days. In those patients with frequent courses of steroids, osteoporosis prophylaxis should be considered.
Antibiotics should be prescribed in those with increased sputum volume or purulence unless there is other clinical evidence of infection (e.g. pyrexia, high CRP) or consolidation on CXR. In the absence of pneumonia, a single antibiotic given orally is appropriate for all patients able to take enteral medication. Choice of antibiotic will be determined by local policy and is influenced by recent previous antibiotic therapy, previous sputum results, and recent hospitalization.
Consider only in patients with a severe exacerbation who are not responding adequately to nebulized bronchodilators, particularly those with predominant wheeze. Aids with bronchodilation and respiratory drive. A loading dose should not be given to patients who were on oral theophylline prior to admission. Aminophylline levels should be measured within 24 h of starting treatment and daily thereafter.
Treatment of acute respiratory failure
NIV has been shown to reduce mortality and hasten recovery in AECOPD patients presenting with hypercapnic respiratory failure compared with standard medical care. It reduces the need for intubation and has a lower complication rate than treatment with invasive ventilation. It should be used as the treatment of choice in persistent hypercapnic ventilatory failure (pH of <7.35 and a PaCO2 of >6 kPa) despite optimum medical therapy, including controlled oxygen. It is important to be aware of iatrogenic hypercapnic acidosis caused by the administration of high-concentration oxygen. Such patients often improve once the FiO2 is lowered without the need for NIV.
NIV should be delivered on a dedicated unit with appropriate levels of monitoring and staff training/experience. This usually means intensive treatment unit (ITU)/high dependency unit (HDU) or a high-monitoring bay on an admission or respiratory ward. Prior to commencement of NIV, the ceiling of therapy should be agreed, in particular if invasive ventilation on ITU is to be commenced if the patient is deteriorating despite NIV. Patients with a pH of <7.25 are at increased risk of treatment failure with NIV and, if appropriate, should be treated on ITU or considered for invasive ventilation at the outset.
Assessment of COPD patients should include functional status, BMI, use of LTOT, comorbidities and previous admissions for ventilation, in addition to age, and FEV1. Patients with good pre-exacerbation functional status and no clinically significant comorbidities who are deteriorating despite maximal medical therapy, including NIV, have a mortality rate of ~25%, which compares favourably with that of patients requiring invasive ventilation for other causes of acute respiratory failure. However, the prognosis deteriorates in patients requiring >72 h of ventilation. NIV has been used to assist weaning patients from invasive ventilation.
There is a lack of good evidence for the benefit of physiotherapy in AECOPD. However, it is of value in patients with significant sputum production, particularly when using a positive expiratory pressure mask to assist coughing.
Opioids (initially morphine sulfate solution 2.5 mg up to 4-hourly) should be given to patients with dyspnoea that is not responsive to other therapy. This treatment is also useful for cough. Opioids should not be reserved solely for patients who are in the terminal phase of their illness. Where anxiety is a major factor, benzodiazepines can also be considered (e.g. lorazepam 0.5–1 mg up to 8-hourly). The palliative care team should be involved.
Following admission with AECOPD, recovery is slow, taking on average up to 14 days, with approximately 14% of patients symptomatic still at 35 days, whilst a small percentage of patients never regain their baseline functional level. In the UK, the in-hospital mortality associated with AECOPD is ~8%, with a third of patients readmitted within 3 months and a 3-month mortality rate of ~15%. For patients requiring either NIV or admission to ITU, the 1-year mortality is ~50%. In stable COPD, prognosis can be calculated using the BODE score (scoring 0–10 for BMI, FEV1, MRC dyspnoea score, and exercise capacity [6-min walk]), with a hazard ratio per one point increase in BODE score of 1.34 (1.26–1.42, P <0.001, 95% CI) for death from any cause.
History and definition
The adult (now more correctly termed acute) respiratory distress syndrome was first described in a case series of only 12 patients from Colorado in 1967. The North American–European Consensus Conference (NAECC) proposed that the syndrome be defined as the acute onset of refractory hypoxaemia in association with bilateral pulmonary infiltrates with no evidence of elevated left atrial pressure (Table 18.4) and this has been used as entry criterion in to many clinical trials. It has been superseded by the Berlin definition. The Berlin definition overcomes perceived deficiencies in the previous NAECC definition by stipulating a requirement of at least 5 cmH2O of PEEP or CPAP, considering alternatives for air-space shadowing and enabling patients with heart failure to fulfil the diagnostic criteria. It also categorizes patients into degrees of severity based on the degree of hypoxaemia as assessed by the PaO2/FiO2 ratio. These subgroups map to increasing mortality (25–45%) in an historical case series. Nevertheless, postmortem examination of patients who fulfilled the Berlin definition demonstrate that it is not specific for diffuse alveolar damage, which is often considered the pathophysiological correlate of the inflammatory driven non-cardiogenic pulmonary oedema that was first described. Diffuse alveolar damage was only present in 12%, 40%, and 58% of cases that fulfilled the definition for mild, moderate, and severe ARDS, respectively.
Table 18.4 Definition of acute lung injury and ARDS
NAECC definition 1994
Berlin definition 2015
Onset within 1 week of insult
Bilateral air space shadowing
Bilateral opacifications not fully explained by effusion, lobar/lung collapse, or nodules
Pulmonary artery wedge pressure <18 mmHg
Respiratory failure not fully explained by cardiac failure or fluid overload
PaO2/FiO2 ratio <26.7 kPa (200 mmHg)
PaO2/FiO2 <40 kPa (300 mmHg)
PaO2/FiO2 <26.7 kPa (200 mmHg)
PaO2/FiO2 <13.3 kPa (100 mmHg)
Causes and risk factors
The likelihood of developing ARDS depends on the type and number of predisposing conditions and on patient characteristics. For example, predisposing factors include alcoholism and emerging genetic polymorphisms, whilst diabetes mellitus is protective. The Lung Injury Prediction Score may help define patients who are at more risk of developing ARDS. Although the causes of ARDS may be divided into direct and indirect injuries (Table 18.5), outcomes are similar if other variables are controlled for.
Table 18.5 Clinical risk factors for ARDS
Direct lung injury
Indirect lung injury
Sepsis syndrome (40%) and shock
Aspiration of gastric contents (20%)
Thoracic trauma/pulmonary contusion
Blood product transfusion**
Inhalation injury (smoke, toxin, near drowning)
Reperfusion injury (lung transplant, pleural effusion drainage)
Drug overdose/drug reaction
Fat embolism syndrome
Pregnancy-related (eclampsia, amniotic fluid embolism)
Tumour lysis syndrome
Head injury/raised intracranial pressure
Figures in parentheses are the approximate percentage of patients with single risk factors that develop ARDS.
*For patients with pneumonia admitted to an ICU.
**For the transfusion of 15 units of blood in 1 day.
Epidemiology and incidence
A recent survey in a defined region of the USA reported that the incidence and mortality of ARDS increases with age from 16 per 100 000 person-years and 24% for teenagers to 306 per 100 000 person-years and 60% for those over 75 years. The majority of patients with ARDS have either been weaned from ventilatory support or have died within the first 10 days; ~10% of patients require support for more than 1 month. Mortality rates from most observational studies vary between 35% and 60%, although this will vary depending on the age of the patient and the presence of non-pulmonary organ dysfunctions, particularly shock and hepatic failure. In specialist centres, survival rates have improved over the past 20 years. Most ARDS patients tend to die with rather than from respiratory failure and, despite severe acute lung damage, chronic respiratory failure afflicts a very small proportion of survivors. Chronic weakness and neuropsychiatric problems that may be permanent are the greatest barrier to survivors returning to their normal lives.
The clinical criteria used to define the syndrome are vague, e.g. those used to exclude cardiogenic pulmonary oedema, which is the most important differential. Numerous conditions may present as ARDS despite not sharing the characteristic pathology (diffuse alveolar damage) and pathophysiology: acute neutrophilic inflammation dysfunction of the alveolar–capillary membrane causing pulmonary oedema; microvascular dysfunction causing ventilation–perfusion mismatching and hypoxaemia; and fibroproliferation. Some of these less common conditions, such as acute eosinophilic pneumonia, acute interstitial pneumonitis, cryptogenic organizing pneumonia, diffuse alveolar haemorrhage, and major pulmonary embolism, have specific treatments, emphasizing the importance of diagnosing the underlying cause of ARDS. Other conditions may be managed differently because of their relatively poor prognosis, e.g. lymphangitis carcinomatosa. An algorithm defining the routine investigation of ARDS based on local expertise and availability and prevalent pathogens is useful.
Clinical features and investigations
The primary aim of the initial clinical assessment is to identify the underlying causes of ARDS and organ system failures that require urgent support. Exclusion of cardiogenic pulmonary oedema is based on the patient’s history, CXR, and ECG in the first instance, although further information may be obtained from a pulmonary artery catheter and echocardiogram in selected cases. Thoracic CT demonstrates characteristic appearances in ARDS, with an indirect cause and evidence of the initial insult when the cause of ARDS was pulmonary. Subsequent assessments should focus on detecting the complications of ARDS and critical illness, most notably hospital-acquired infection. Thoracic CT not uncommonly reveals pathology that is not evident on a plain chest radiograph, e.g. pneumothorax, pleural effusion, pneumonia, and lung abscess.
Despite the large number of studies investigating specific therapies for patients with ARDS, few have been shown in large clinical trials to improve clinical outcomes. The mainstay of management of ARDS is supporting organ function and minimizing harm, while treatments are directed at the underlying cause. Strategies shown to improve mortality do so mainly through a reduction in ventilator-associated lung injury (VALI). These include the use of low tidal volume ventilation, prone positioning, early neuromuscular blockade, and extracorporeal support. However, improvements in the survival of these patients in specialist centres preceded the widespread adoption of these strategies and emphasize the importance of optimizing supportive care. Carrying out clinical trials in a highly heterogeneous critically ill population of patients is fraught with pitfalls, which are exacerbated by the loose criteria that define the syndrome.
Prevention of ARDS
A large proportion of ARDS develops in hospital, thus highlighting the importance of prevention in patients at risk of developing ARDS. Lower tidal volume ventilation, avoidance of unnecessary blood product transfusion, and excessive fluid administration in at-risk groups, such as patients undergoing major surgery, are associated with a reduction in the development of ARDS.
General supportive care
In the absence of specific treatments for ARDS, management involves aggressive treatment of the underlying causes and prevention and treatment of the complications of ARDS and critical illness. In essence, the objective is to buy time and to optimize conditions for the lungs to recover. Thus, prophylaxis against stress ulceration, venous thrombosis, and pressure ulcers should be administered as indicated. Acute right heart dysfunction in patients with ARDS is common, resulting from high levels of positive pressure ventilation, pulmonary vasoconstriction, microvascular thrombosis, and sepsis, amongst others, and may require specific management. Inhaled vasodilator therapies such as nitric oxide (NO) and prostacyclins improve oxygenation, reduce pulmonary vascular resistance, and improve right heart function, but have not been shown to improve mortality or other longer-term outcomes. Oxygen therapy should be titrated to specific goals to maximize oxygen delivery whilst avoiding hyperoxia, which may exacerbate lung injury, and which is associated with increased mortality in several critical care settings (although not specifically in patients with ARDS). Consideration should be given to transferring patients with severe ARDS and inadequate gas exchange despite optimal management, including ‘protective’ ventilation, to regional high-volume centres that can offer extracorporeal support, as this is associated with improved outcome.
Non-pulmonary sepsis and pneumonia are amongst the most common causes of ARDS. Conversely, sepsis and ventilator-associated pneumonia (VAP) are common complications of ARDS. VAP is difficult to diagnose in patients with ARDS because of the frequent coexistence of pulmonary infiltrates and raised indices of inflammation. The importance of preventative measures, including oropharyngeal antiseptics and prompt aggressive antibiotic treatment, cannot be overemphasized.
Patients with respiratory failure should receive a high-fat, low-carbohydrate diet to reduce CO2 production and thus ventilatory demand. Enteral nutrition removes the disadvantages of parenteral feeding, such as catheter-related infection and impaired hypoxic pulmonary vasoconstriction. The advantages of enteral feeding include improved gut barrier function (decreasing translocation of bacteria and their toxins) and a decreased incidence of stress ulceration. Small studies investigating so-called ‘immunomodulatory diets’, containing anti-inflammatory and antioxidant supplements, have demonstrated benefits in respiratory parameters and the duration of mechanical ventilation, but not mortality, for which larger multicentre studies will be required.
Sedation and paralysis
The use of neuromuscular blocking drugs for the first 24–48 h of mechanical ventilation in patients with ARDS may improve outcome by reducing patient-ventilator dyssynchrony and VALI. Protocols that include regular interruption of sedative infusions shorten the duration of mechanical ventilation and facilitate weaning.
Whilst pulmonary oedema in ARDS is not caused by fluid overload or high left atrial pressure, the high permeability of the pulmonary microvasculature results in leakage of osmotically active molecules into the interstitial space. The formation of oedema, therefore, depends directly on hydrostatic pressure, because osmotic forces are less able to retain fluid in capillaries. Whilst removing lung water improves respiratory function, dehydration of critically ill patients may precipitate multiple organ failure. A recent study compared the effects of liberal and conservative fluid administration strategies in 1000 patients with acute lung injury. Although there was no effect on mortality, the conservative strategy improved lung function and shortened the duration of mechanical ventilation without increasing non-pulmonary organ failures.
Corticosteroids may modify the course of lung injury by reducing the activity of a variety of proinflammatory and fibrogenic mediators. However, their administration is not beneficial early in the course of the syndrome. Several small studies suggested clinical benefits of extended moderate- to high-dose methylprednisolone when given to patients with ARDS at least 1 week after diagnosis. A recent randomized, blinded trial involving 180 patients who had acute lung injury for at least 7 days demonstrated no effect on mortality of methylprednisolone versus placebo. However, methylprednisolone increased the number of ventilator-free and shock-free days, with an improvement in oxygenation and compliance. Methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness. Unfortunately, these data have not ended the controversy over the role of corticosteroids in the treatment of ARDS.
A number of other pharmacological therapies have been the subject of randomized controlled clinical trials in patients with ARDS. These include β-adrenergic agonists (no benefit, possible harm), statins (no benefit), and surfactant (no benefit). Several possible future therapies are under evaluation. For example, vitamin D deficiency may contribute to the development of respiratory failure, suggesting a possible role for vitamin D supplementation to prevent or treat ARDS. Mesenchymal stromal/stem cells, which can modulate the immune response and promote tissue repair after injury, are of interest as a therapy for patients with ARDS, with early-phase clinical trials under way.
Longer-term outcomes after ARDS
Many patients suffer physical, psychological, and cognitive problems for several years after ICU discharge following ARDS. Although pulmonary function tests return to near-normal, physical functioning can remain below normal for up to 5 years, and approximately 20% have cognitive impairment. Access to critical care follow-up services may facilitate identification of these issues, and referral for ongoing patient and family support may be required.
Despite the heterogeneous nature of ARDS, the ARMA ARDS network study of 860 patients demonstrated the dramatic effect that ventilatory management has on survival in this syndrome. In essence, invasive mechanical ventilation (MV) is a necessary evil that is required in almost all cases but which further damages the lung and contributes to multiple organ failure.
Ventilator-associated lung injury
Experiments carried out 30–40 years ago demonstrated that high tidal volume and high-pressure ventilation caused lung injury in healthy animals and that the previously damaged lung was particularly susceptible to these effects. Similar models implicated the effects of overdistension (volutrauma) as opposed to high airway pressure (barotrauma) and demonstrated the injurious effects of cyclic expansion and collapse of lung units deficient in surfactant activity (atelectotrauma). The ‘biotrauma hypothesis’ addresses the question of how injurious MV affects mortality when only a small minority of patients succumb to respiratory failure. The hypothesis is supported by clinical studies demonstrating that injurious as opposed to protective MV was associated with the detection of increased concentrations of inflammatory mediators in bronchoalveolar lavage and plasma. From these studies, it can be inferred that injurious MV stimulates the production of inflammatory mediators that spill over from the lung into the systemic circulation and contribute to multiple organ failure.
It is now accepted that MV is inevitably damaging to the injured lung and it is neither necessary nor desirable to strive to achieve normal ABGs in patients with ARDS. The ARMA study demonstrated improved survival associated with using a tidal volume target of 6 as opposed to 12 ml/kg predicted body weight (PBW). However, it is not known whether 6 ml/kg is the optimal tidal volume and there does not appear to be a threshold tidal volume or safe plateau pressure below which there is no advantage in decreasing tidal volume. The effects of PEEP (recruitment of collapsed lung, reduced intrapulmonary shunting, and improved oxygenation) are particularly beneficial in ARDS because large parts of the lung are collapsed owing to deficient surfactant activity. Despite concerns that PEEP might have detrimental effects, primarily by overdistending compliant alveoli or by decreasing venous return, right ventricular function and oxygen delivery, high levels of PEEP improved oxygenation without increased barotrauma risk. Furthermore, a meta-analysis of three randomized controlled trials (RCTs) suggested that high-PEEP benefits patients with moderate to severe ARDS. The application of high airway pressure for a limited period (recruitment manoeuvres) confers short-term physiological benefit only, but may be useful in rescuing patients with life-threatening hypoxaemia.
Alternative modes of respiratory support
There is very little evidence to favour one ventilatory mode over another in adult patients with ARDS. High-frequency ventilation, aiming to minimize tidal volume while maintaining recruitment through a high mean airway pressure, did not reduce mortality in RCTs or subsequent meta-analyses.
Perhaps the ultimate means of resting the injured lung is to perform extracorporeal membrane oxygenation (ECMO). This technique requires that the patient’s blood passes across a membrane to supplement gas exchange. Because of associated complications, this has traditionally been a salvage therapy, which is only of proven benefit in children. However, newer devices that just aim to remove CO2 require a less invasive approach and less anticoagulation, suggesting that this and similar devices may have an increasing role in the future. Patients with severe ARDS associated with influenza A pneumonia managed in regional ECMO centres had improved mortality and this care was cost-effective. These data have lead to the commissioning of regional ECMO centres in the UK.
Adjuncts to ventilatory support
In many cases of ARDS, especially those with an indirect non-pulmonary cause, there is a predominance of collapse and consolidation in dependent lung regions. Turning patients from supine to prone improves ventilation–perfusion matching and significantly affects gas exchange in approximately two-thirds of cases of lung injury. Furthermore, the weight of the mediastinum is removed from the left lower lobe, secretion clearance may be enhanced, and VALI be mitigated. Recent large studies and meta-analyses have demonstrated benefits in survival and duration of MV with prone positioning for periods in excess of 12 h. Inhaled vasodilators, nebulized prostacyclin, or NO also improve oxygenation in approximately two-thirds of cases of lung injury, but have repeatedly failed to improve survival in large studies.
Recommendations for instituting invasive MV in patients with ARDS
It is not possible to describe ideal ventilator parameters for all patients; MV settings need to be individualized and changed with time to suit the patient’s condition. This is best achieved with an empirical approach and patience; however, some guidelines may be applied.
• Tidal volume of 6 ml/kg PBW, calculated as follows: for men, PBW = 50.0 + 0.91 (height in cm – 152.4); and for women, PBW = 45.5 + 0.91 (height in cm – 152.4). If the plateau pressure is >30 cmH2O try to decrease tidal volume further if gas exchange targets can still be met. This may be unnecessary if there is an extrapulmonary cause of restriction, for example abdominal distension.
• Respiratory rate of 20/min, which will tend to mitigate respiratory acidosis, but ensure that expiration is completed before the subsequent inspiration starts to avoid breath stacking.
• Accept a pH >7.2 and do not worry about hypercapnia unless there is concurrent intracranial hypertension or other contraindication. Respiratory acidosis is generally well tolerated unless the rise in CO2 tension is rapid.
• Oxygen saturation target of 88–92% to minimize oxygen toxicity.
• Set PEEP between 14 and 8 mmHg; start at a high level and decrease until the compliance or oxygenation deteriorates.
• Whilst muscle relaxants and full sedation maybe required initially to mitigate dyssnchrony and VALI, these should be withdrawn or minimized as soon as possible to avoid neuromuscular sequelae.
• High PEEP and prone positioning used early and for time periods in excess of 12 h are recommended for patients with moderate to severe ARDS.
• Refractory hypoxaemia may be improved by the administration of inhaled vasodilators like nitric oxide.
Asthma is a heterogeneous disease, clinically defined by the presence of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity. These symptoms are usually associated with widespread but variable airflow limitation, which is at least partly reversible either spontaneously or with treatment. Airway inflammation plays a key role in pathogenesis of asthma and is associated with an increase in airway hyperresponsiveness to a variety of stimuli, e.g. allergens.
A diagnosis of asthma is often made on clinical grounds alone. A robust diagnostic approach, however, should incorporate the following: 1) detailed assessment of clinical features, particularly to identify atypical features that highlight alternative diagnoses; 2) pulmonary function testing, including spirometry ± bronchodilator reversibility testing and serial peak flow rate (PEFR) measurements or an assessment of airways hyperreactivity (i.e. with bronchoprovocation testing) in those with normal lung function; 3) an assessment of airway inflammation, e.g. fraction of exhaled nitric oxide (FeNO).
The differential diagnosis for asthma is broad and often patients with other chronic respiratory diseases will have been initially treated as ‘asthmatic’. Specifically, other causes of dyspnoea and wheeze should be considered; these include structural abnormalities within the airway tree causing wheeze (e.g. mass lesions), intermittent closure of the upper airways (e.g. vocal cord dysfunction), bronchiectasis, and non-respiratory causes of wheeze (e.g. heart failure). Clinical assessment should focus on identifying these conditions with logical investigations arranged as indicated.
Differentiating COPD from asthma has historically been deemed to be important and performed based on an evaluation of the clinical features; i.e. smoking history, age, and progressive non-variable symptoms all favouring COPD. In a proportion of patients it can be difficult to differentiate asthma from COPD and, whilst this may be of interest in a research or epidemiological setting, it is pragmatically most useful for the clinician to focus on whether there is active airway inflammation and variable airflow obstruction and thus target treatment accordingly.
History: key points
Cough, wheeze, breathlessness, chest tightness:
• Variability with episodic symptoms: worse at night or early morning, variability over time.
• Triggers: classical triggers include exercise, allergens, or cold air exposure.
• Medications: aspirin/non-steroidal anti-inflammatory drugs can precipitate asthma in a small proportion of patients.
• Atopy: personal or family history.
Take a thorough occupational history and, if relevant, establish if symptoms improve on leave from work.
• Smoking history.
• Exposure history at home (pets, etc.).
Examination: key points
• Cardiorespiratory examination is often normal and does not rule out asthma.
• Widespread expiratory polyphonic wheeze may be present.
• This wheeze differs from the monophonic wheeze of fixed airway narrowing or upper airway wheeze, heard best over the neck.
An assessment of inhaler technique and treatment adherence should be part of clinical assessment.
Pulmonary function testing may be normal. An FEV1/FVC <0.7 is indicative of obstructive airways disease. If obstructive, it should be followed by a bronchodilator reversibility test. An increase in FEV1 of both ≥200 ml and ≥12% is usually taken to provide evidence of bronchodilator reversibility.
FeNO testing is recommended to assess airway inflammation. If levels are >40 ppb (>35 ppb in children) this is considered a positive test.
If FeNO is equivocal, serial PEFR measurements with >20% variability are indicative of asthma. An evaluation of the presence of eosinophilia (i.e. > = 0.3) on full blood count testing is useful in identifying patients with heightened inflammation that is likely to be more responsive to corticosteroid.
If uncertainty still exists, bronchial provocation testing with methacholine or histamine challenge can be helpful. A provocative concentration causing a 20% fall in FEV1 (PC20) of <8 mg/ml indicates airways hyperreactivity and is supportive of a diagnosis in the correct clinical context.
Imaging is useful to exclude other diagnoses and a chest radiograph is the initial investigation of choice in any patient presenting with new respiratory symptoms.
Goals of treatment are freedom from symptoms of asthma, minimizing exacerbations, eliminating impairment of daily activities, reducing pharmacological side-effects, optimizing lung function (FEV1 and/or PEFR >80% predicted or best) and patient/carer education about asthma, its prevention, and early treatment. These are achievable through:
• Regular monitoring of symptoms. It is recommended to use a validated questionnaire in clinic (Asthma Control Questionnaire or Asthma Control Test).
• Regularly monitor lung function or PEFR variability.
• Avoiding and controlling asthma trigger factors.
• Appropriate pharmacological therapy.
• Patient education (including asthma management plans and inhaler technique).
A stepwise approach aims to abolish symptoms and optimize lung function by initiating treatment at the level/dosing most appropriate to achieve this. As symptoms emerge, early control and maintaining it by stepping up treatment as necessary and stepping down when good control is established.
‘Relievers’: short-acting β-agonists (SABAs) for short-lived relief in all with symptomatic asthma. Anticholinergics can be added in acute excerbations.
‘Preventers’: inhaled corticosteroids (ICS) should be used regularly. Theophylline or leukotriene receptor antagonists can be used as ‘add-on’ treatments at ≥step 3 (see section on ‘Stepwise approach’). Long-acting antimuscarinic agents (e.g. tiotropium) are used at step 4.
Specific therapies: in severe asthma monoclonal anti-IgE (e.g. omalizumab), bronchial thermoplasty; seek specialist advice.
Stepwise approach (from Global Initiative for Asthma)
Step 1: mild intermittent asthma; SABA as required, consider low dose ICS.
Step 2: regular preventer therapy; ICS 200–800 µg/day beclometasone dipropionate equivalent. Consider Leukotrine Receptor antagonist (LTRA).
Step 3: Low dose ICS/LABA. Consider adding LTRA or theophylline. Beyond Step 3, consider changing reliever from SABA to ICS/LABA where LABA is formoterol.
Step 4: Medium/high dose ICS/LABA. Consider adding tiotropium, LTRA or theophylline.
Step 5: High dose ICS/LABA. Utilise other controller options (LTRA, theophylline, tiotropium). Add low dose oral corticosteroids.
Refer patient for specialist care. There are now multiple ‘biologic’ therapeutics for severe/treatment refractory asthma. Patients should be referred to a dedicated severe asthma service at step 5.
Acute severe asthma
Acute severe asthma remains an important cause of preventable mortality. The predictors of morbidity include poor perception of severity, inadequate asthma management, and previous ICU admission (Table 18.6). International guidelines for management are published.
Table 18.6 Clinical features of acute severe asthma
Respiratory effort/rate (RR)
Cannot complete sentence in a breath
Feeble effort/silent chest
Heart rate (HR)
HR ≥110/min; arrhythmias, bradycardia, hypotension
Arterial blood gas
PaO2 >8 kPa
PaO2 <8 kPa
PaCO2 ≤4.6 kPa
Normal PaCO2 (4.6–6.0 kPa)
Cyanosis, exhaustion, confusion, coma
Near fatal asthma (or status asthmaticus) is defined as having raised PaCO2 and/or requiring MV with raised inflation pressures. Patients with increasing use of bronchodilators prior to admission, with one or more psychosocial factors, and with chronic severe asthma are at greater risk of death from their asthma.
Immediate treatment: O2 (high flow, aiming sats 94–98%), nebulized bronchodilator (salbutamol 5 mg ± ipratropium bromide 500 µg [flow rate for nebulized medication is 6 l/min]), intravenous [IV] hydrocortisone 100 mg bd–qds (prednisolone 40–50 mg PO od for at least 5 days until recovery).
Review: monitor PEFR, O2 saturation, repeat ABG if no improvement, check serum K+. If no response, further back-to-back or continuous nebulized bronchodilators.
Life-threatening: several IV therapies have been employed for bronchodilation and include IV magnesium Mg2+ (20 ml 10% MgSO4) over 20 min, or IV salbutamol (250 µg slow bolus), and/or IV aminophylline 500–750 mg in normal saline over 24 h (monitor levels). The choice of IV therapy will depend on local experience and availability; however, IV magnesium and aminophylline are favoured. Drug levels and blood magnesium levels should be checked. Adequate fluid resuscitation is important.
Intensive care admission is required if: requiring ventilator support, acute severe or life-threatening asthma not responding to therapy; deteriorating PEFR, persisting or worsening hypoxia, hypercapnia, acidaemia, exhaustion, or low Glasgow Coma Scale. Only consider NIV in an ICU setting with senior experts and only if there is no indication for immediate intubation.
Approximately 2–4% of all patients hospitalized for acute severe asthma require supportive invasive mechanical ventilation (IMV). Although life-saving, mechanical ventilation and its associated interventions can also cause morbidity (direct complications and postcritical care recovery issues) and mortality.
The decision to institute IMV is a bedside clinical judgement guided both by the patients’ cardiorespiratory response trajectory to appropriate treatment, as well as absolute indications, such as a reduced level of consciousness, respiratory failure denoting impending exhaustion and cardiorespiratory arrest.
IMV in an asthmatic patient requires the development of a strategy to overcome the critical pathophysiological features involved to reduce gas trapping and prevent dynamic hyperinflation. Potential barotrauma is thereby limited while maintaining adequate oxygenation, at the expense of normocarbia if necessary, while waiting for medical therapy to work.
Key pathophysiological principles
The main issue to overcome is the high airway resistance (bronchospasm, airway inflammation/oedema, and mucus plugging) resulting in airflow obstruction, and reducing expiratory flow. This prolongs expiratory time such that the next breath taken interrupts exhalation of the previous inspired tidal volume, resulting in gas trapping (positive end-expiratory alveolar pressure) that leads to pulmonary hyperinflation.
In life-threatening asthma, rapid respiratory rates coupled with changes in pulmonary mechanics and dyssynchronous respiratory muscle activity exacerbates this process. The ensuing ‘breath stacking’ causes progressive dynamic hyperinflation and the generation of intrinsic (or ‘auto’) positive end-expiratory pressure (iPEEP) within the alveoli and an increased risk of barotrauma.
The increased lung volumes, which can approach total lung capacity, reduce ventilatory efficiency because of diaphragmatic flattening, increasing work of breathing and respiratory muscle fatigue (primarily intercostal muscles). With lung volumes approaching closing capacity, airway closure can occur, causing mismatched ventilation–perfusion, potentially leading to hypoxaemia, but primarily a failure in CO2 elimination from inadequate alveolar ventilation resulting in the characteristic impairments in gas exchange seen on ABGs. Significant levels of hypoxia should advocate a low threshold for the pursuit of additional pathology.
As yet the role of NIV in the acute severe asthmatic remains inconclusive as a defined potential supportive therapy. There is a growing evidence base to suggest that it represents a safe remedy that improves lung function, reduces the need for endotracheal intubation, and, in patients with moderate hypercapnic acidosis, has relatively low complication rates.
Currently, in a more severe cohort, it would be prudent to consider a trial of efficacy in carefully selected patients (in the absence of any relative contraindications to NIV) in an appropriately monitored high care setting for an agreed time period with strictly defined clinical and biochemical criteria of success (e.g. respiratory rate, work of breathing, pH and CO2 clearance).
Instituting IMV in the acute severe asthmatic should not be taken lightly. Optimal intubating conditions (adequate venous access, non-invasive monitoring) with an appropriate induction agent and neuromuscular blockade (NMB) (e.g. suxamethonium or rocuronium) should be attained. To prevent possible life-threatening complications owing to the potentially hazardous physiological consequences resulting from the institution of positive pressure ventilation, as well as manipulation of the airway leading to increased airflow obstruction due to exaggerated bronchial responsiveness, laryngoscopy and endotracheal intubation should, if possible, be performed semi-electively in experienced hands, preferably with a large bore ETT (size ≥8 mm).
Hypotension is a common multifactorial consequence. Pre-existing hypovolaemia in conjunction with the use of anaesthetic agents (reduction in sympathetic vasomotor tone), a reduction in venous return, and increased right ventricular afterload resulting from high intrathoracic pressures precipitated by the application of positive pressure ventilation predispose to its development. It can be severe enough to result in complete loss of cardiac output (mimicking that occurring in a tension pneumothorax) and should be anticipated with plans made to mitigate its occurrence with fluid preloading and vasopressors to hand. Consideration should be given to disconnecting the patient from the circuit (possibly with the addition of pressure on the chest wall to assist expiratory flow) to allow full passive expiration should this complication occur during induction (as well as during subsequent management on the ICU).
As articulated previously the main challenge to overcome is high airway resistance given that lung compliance (non-obese) is usually relatively normal. Therefore, there will be a large fall in pressure (Pres) across from the major airways (Peak airway pressure [Paw] ~ a measure of large airway resistance) to the alveolus, which will be considerably lower (Plateau pressure [Pplat] ~ influenced by the degree of hyperinflation [a component of which will be iPEEP]) (Figure 18.1). Consequently, while the high Paw is important and reflects the degree of airway obstruction that responds to the bronchodilator therapy, it is less important in terms of ventilator-induced injury, e.g. barotrauma (pneumomediastinum and pneumothorax) as it does not reflect the actual pressure transmitted to the alveolus. As a result, adjustments to the ventilator should not be specifically geared toward reducing the Paw but more toward controlling the Pplat [inspiratory hold on ventilator].
The IMV delivered minute ventilation (respiratory rate × tidal volume) is therefore the primary determinant of hyperinflation owing to the limiting influence of airways resistance on expiration. The ideal ventilation stratagem should include: lung-protective tidal volumes coupled with a slow respiratory rate with prolongation of expiratory time to ensure Pplat limitation (i.e. minimizing dynamic hyperinflation).
This requirement for low minute ventilation may lead to relative hypoventilation and worsening of the hypercapnia that is a consequence of the increased physiological dead space (alveolar distension) ventilation that is part of the disease process. This is generally well tolerated (i.e. permissive hypercapnia) so long as adequate oxygenation is achieved and is acceptable in the absence of contraindications (particularly intracranial pathology or myocardial ischaemia).
In view of the difficult airway hyperreactivity, tendency to develop dynamic hyperinflation, and the goal of resting the fatigued respiratory muscles, controlled modes of ventilation are usually required in conjunction with heavy sedation (± NMB) in the immediate postintubation period. Although either pressure- or volume-controlled modes can be utilized, the former will require the setting of significantly high inflation pressures to overcome airway resistance and achieve appropriate tidal volumes. This may present a problem if the patient’s condition improves suddenly and can result in severe barotrauma and volutrauma, i.e. this author prefers using a volume- or pressure-regulated volume control setting.
iPEEP [expiratory hold on ventilator] increases the magnitude of the drop in airway pressure that the patient must generate to trigger a breath, thereby increasing the patient’s workload. Careful application of extrinsic PEEP (ePEEP) at levels less than the iPEEP will theoretically reduce this gradient and facilitate triggering to reduce the work of breathing. Thus, ventilator-set ePEEP levels up to 70% of iPEEP can often be helpful in spontaneously breathing patients if set, monitored, and adjusted at the bedside. Note that measurements of iPEEP may be underestimated in the event of severe widespread airway collapse (closing capacity) during expiration. Judicious application of the above principle can also be attempted by experienced clinicians in apnoeic mandatorily ventilated patients in that it may stent the airways open, preventing premature collapse and thereby permitting continued unobstructed airflow, allowing lung deflation (‘waterfall effect’). However, ePEEP can also be detrimental and should generally be avoided in this patient cohort (ventilated and paralysed) and set at 0–1 cmH2O (zero end-expiratory pressure). In view of the potential for further dynamic hyperinflation, which may go unrecognized, one should be prepared to decompress manually if necessary (by disconnecting the patient from the ventilator tubing momentarily).
Clinicians should use clinical judgement in adjusting ventilator settings to determine whether the main objective priority is improving the respiratory acidosis or reducing gas trapping and hyperinflation. Table 18.7 provides an example of typical ventilator settings in a volume-controlled (pressure-limited or not) mode of ventilation.
Table 18.7 Typical ventilator setting and targets for acute severe asthma
≤8 ml/kg ideal body weight
ZEEP (Mandatory mode)
ePEEP (Spontaneous mode)
Zero PEEP (no ePEEP)
25–70% of the iPEEP
Inspiratory plateau pressure (Pplat#)
Peak airway pressure (Paw)
*An increase in expiratory time can only be achieved if the inspiratory time is decreased and the inspiratory flow increased (assuming tidal volume and respiratory rate are kept constant); as a result, peak airway pressure will rise (i.e. change alarm settings to prevent dumping).
#Given the normality of lung compliance, assuming reasonable tidal volumes, the Pplat will only be high if there is gas trapping. Therefore setting a different upper limit (≤20–30 cmH2O) to that used in ARDS is acceptable.
Sedation and anaesthesia
Sedation and anaesthesia may be required to optimize patient–ventilator interaction; personal experience and local practice account for the variation in agents used. Those guiding the choice should rationalize the possibility of rapid improvement, allowing extubation within 24–48 h (median duration of IMV ~3 days), and limit the use of agents with residual effects that may affect appropriate daily sedation breaks and physical therapy to prevent the development of critical care polymyoneuropathy. Propofol, with its rapid onset and offset, together with opiates, represent good coinduction agents for intubation and short-term sedation. Although boluses of the latter can potentially cause histamine release with worsening bronchoconstriction, using fentanyl or alfentanil (rather than morphine) diminishes this concern. Intravenous ketamine, with its bronchodilator and sympathomimetic properties, is useful for stable induction and sometimes as infusional maintenance sedation after intubation in the event of persisting severe bronchospasm. The addition of benzodiazepines as adjuncts may be considered in those requiring additional or longer-term sedation.
Neuromuscular blocking agents
The use of neuromuscular agents is necessary to optimize the rapid sequence intubation environment and sometimes to achieve control of ventilation and reduce dynamic hyperinflation. Potential additional benefits include reduction in oxygen consumption and a reduction in CO2 and lactic acid production. The preferred agents are rocuronium, vecuronium, and pancuronium. Although all these neuromuscular blocking agents may cause histamine release in large boluses, potentially worsening bronchoconstriction, long-term muscle relaxation with these agents is associated with lower levels of histamine release compared with atracurium. However, the risk of myopathy is greater with the concomitant use of corticosteroids than without NMB. Therefore, it is preferable to minimize the duration of use and employ intermittent boluses with adequate titration of sedation to achieve a determined sedation score, rather than continuous infusions.
β2-adrenoceptor agonists can be delivered to ventilated patients by inline nebulization or metered-dose inhalers with an appropriate spacer in the inspiratory limb of the ventilator circuit. The amount of drug reaching the airways depends on the nebulizer design, driving gas flow, characteristics of the ventilator tubing, size of the ETT, and simultaneous circuit humidification. The latter is associated with less efficient drug delivery and should be momentarily paused during bronchodilator administration.
Weaning from a mandatory mode to spontaneous ventilation as soon as possible is usually commenced following signs of stabilization in ventilation typified by reductions in dynamic hyperinflation (reduced airway resistance [Paw] and gas trapping [Pplat]) in association with clinical signs (e.g. CO2 clearance and wheeze). This often appears to be a well-defined time specific to patients. Albeit difficult to predict, sometimes it is heralded by a lack of need for frequent changes in ventilator parameters, and the sudden production of copious secretions, thought to be related to the loosening of trapped sputum plugs as bronchiolar bronchoconstriction and inflammation settle. Preparation for extubation results from the use of spontaneous breathing trials and recognition of the patient’s improvement in pulmonary ventilation capacity to balance against potential respiratory demands (e.g. secretion load).
Other techniques used for severe asthmatics on mechanical ventilation
Despite use of the treatments mentioned earlier, some patients continue to demonstrate refractory bronchoconstriction, extreme hyperinflation, and mucus plugging. Various additional methods have been used to alleviate these factors. The routine use of these therapies cannot be recommended based on the current available evidence.
Inhalational volatile anaesthetic agents (e.g. isoflurane and sevoflurane) are potent bronchodilators. This adjunctive effect can be used for mask induction in severe asthma as well as maintenance sedation in refractory cases. A meaningful response to their use should be seen within a short period of implementation and persisting application in the absence of this effect is not warranted. Their hypotensive effects, the requirement for scavenging, and minimum alveolar concentration monitoring limits the use of these agents within the ICU in the absence of specific inline conservation devices (This author would recommend Creatinine Kinase (CK) monitoring).
Bronchoscopic lavage with mucolytics (e.g. acetylcysteine, recombinant DNAse) has been reported in successfully dealing with mucus plug impaction and associated obstruction, resulting in improvements in gas exchange in this patient group. However, the risk:benefit ratio of the procedure with the potential to cause further airway irritation should always be carefully considered. Although the use of expectorants or chest physiotherapy has not been consistently shown to provide any direct benefit, their utility, together with adequate hydration and airway humidification to prevent the desiccation of respiratory secretions, is encouraged.
Adrenaline has both a bronchodilator effect from its β2-adrenoceptor agonist action and an α-agonist vasoconstrictor effect, thus possibly reducing mucosal oedema formation. It is not superior to ‘pure’ β2-adrenoceptor agonists and is not recommended for routine use in the treatment of asthma, particularly with its ability to contribute an added metabolic component to the patient’s acidaemia. However, it may provide additional benefit in non-responding patients and can be given either nebulized (2–4 ml of 1% solution hourly), SC (0.3–0.4 ml 1:1000 every 20 min for three doses) or in extremis IV (0.2–1 mg as a bolus followed by 1–20 µg/min).
The reduced density of heliox (helium and oxygen blend) predisposes to less turbulent airway gas flow. Although this beneficial effect on work of breathing may be potentially leveraged in spontaneously breathing less severe asthmatics. The limitation in maximum O2 fraction (≤40%), its potential to cause ventilator malfunction, and the complex recalibration requirements to prevent inaccuracies in the measurement of gas flow and tidal volume limits its use in the critically ill asthmatic. If a trial is considered, its effects (on CO2 and hyperinflation indices) should be apparent within 15–30 min of implementation and otherwise discontinued.
Extracorporeal life support
Primarily venovenous (VV) ECMO or extracorporeal CO2 removal (ECCO2R) can be used for patients with acute severe asthma complicated by severe hypoxia and refractory respiratory acidosis, respectively, or in the setting of situations complicated by barotrauma. However, this technique is rarely required and large-volume clinical outcome data is as yet unavailable to recommend its use outside situations where risk of death is high.
Patients with acute severe asthma who require IMV have increased in-hospital mortality compared with patients who do not (7% versus 0.2%). They also experience their share of the complications common to critically ill patients, ranging from nosocomial infection to the postcritical care physical and psychological trauma that afflicts a proportion of this patient group. The significant majority of asthma deaths in this setting are related to cerebral hypoxic brain injuries sustained in prehospital cardiorespiratory arrests. Patients who survive to hospital discharge remain at high risk of death. Transfer of care from ICU through to the respiratory ward and asthma clinic follow-up, with discharge planning and personalized asthma management plans, is vital. In addition, critical care follow-up clinic input to give advice about the potential influences that critical illness will have on recovery is also important and should not be neglected.
A pneumothorax is defined as the presence of air in the pleural cavity, and can be classified as either primary or secondary.
• Patients without clinically apparent lung disease. More common in tall thin males (M:F 5:1) with a peak incidence between 10 and 30 years. Most have unrecognized underlying lung disease, with subpleural bullae found in almost all patients who undergo thoracotomy. Cigarette smoking increases the risk by 100 times.
• Spontaneous—underlying lung disease (COPD, asthma, cystic fibrosis, interstitial lung disease, TB, lung abscess, pneumocystis pneumonia).
• Traumatic—penetrating and non-penetrating thoracic and upper abdominal trauma.
• Iatrogenic—pleural biopsy or aspiration, central venous access, mechanical ventilation, percutaneous tracheostomy.
Both primary and secondary pneumothoraces are relatively common reasons for medical consultation and hospital admission. In the critical care population overall, the incidence of pneumothorax is ~3%, although in ventilated patients the incidence can be much higher, and is predominantly related to ventilator-induced barotrauma or invasive procedures (Table 18.8). In general, morbidity and mortality are determined by the underlying condition. However, in the critically ill, pneumothoraces are associated with increased morbidity and mortality.
Table 18.8 Risk factors for pneumothorax in critically ill
High plateau pressures
Interstitial lung disease
Central venous access
Human immunodeficiency virus disease (pneumocystis pneumonia)
ARDS/acute lung injury
Low body weight
Symptoms and signs
Patients commonly present with ipsilateral pleuritic chest pain and dyspnoea. The severity of the symptoms relates to the size of the pneumothorax (small pneumothoraces may be asymptomatic). Patients with secondary pneumothoraces or any tension pneumothorax may have more dramatic presentations, with severe dyspnoea, hypoxia, hypercapnia, and cardiovascular instability. This particularly applies to ventilated patients with their underlying lung pathology and increased risk of tensioning.
Physical examination may reveal:
• Tachypnoea (may be missing in ventilated patients).
• Asymmetrical chest wall movement (decreased expansion on affected side).
• Hyperresonance on percussion.
• Tracheal deviation—towards affected side in simple pneumothorax; away from affected side in tension pneumothorax.
• Subcutaneous emphysema.
• Pulsus paradoxus*.
(*Tension pneumothorax/secondary pneumothorax with severe underlying lung disease.)
Additional findings in ventilated patients:
• Increased peak airway pressures (volume control).
• Sudden reduction in end-tidal CO2.
• Decreased tidal and minute volumes (pressure-‘controlled’ modes).
In the absence of life-threatening cardiovascular compromise, it is advisable to confirm a suspected pneumothorax with a CXR prior to instigating treatment. Classically a pneumothorax appears as a sharp white apicolateral line, beyond which there are no lung markings. In the intensive care patient, however, diagnosis may be more difficult, with anteromedial (38%) or subpulmonic (26%) pneumothoraces being common. In addition, pleural adhesions may result in loculated or encysted pneumothoraces, which may be indistinguishable from bullae. Radiological findings associated with pneumothoraces in this population include:
• Increased lucency over diaphragm/upper abdomen.
• Deep sulcus sign.
• Visualization of the inferior surface of the lung.
• Ovoid hypodense regions.
• Fluid level.
• Temporal changes in line and drain positions.
• Mediastinal air and surgical emphysema.
In patients with significant surgical emphysema, bullous lung disease, or complex chest pathology, CT scanning may be required both for diagnosis and to guide further management.
Radiological signs of tension pneumothorax
• Shift of mediastinum to contralateral side.
• Flattening or inversion of ipsilateral diaphragm.
• Hypoxaemia and mild respiratory alkalosis common.
• Hypercapnia and acidosis dictate emergent management.
Ultrasound can be useful to diagnose a pneumothorax in patients who are unstable or must remain supine, and has been found to be a more sensitive tool than supine chest radiography in trauma patients. A probe placed in the third to fourth intercostal space on the anterior chest can demonstrate signs of a pneumothorax, including:
• Lack of lung sliding movement (dynamic horizontal movement of the pleura sliding over each other during respiration).
• Absence of comet tail artifact.
• Absence of normal seashore sign during M-mode, replaced with stratosphere sign.
• The presence of a lung point—the location at which normal lung sliding disappears and the pneumothorax begins.
Primary spontaneous pneumothoraces: usually well tolerated and, if small (<2–3 cm) and asymptomatic, can be observed and discharged if there is no deterioration after a period of hours. With larger, symptomatic pneumothoraces, aspiration should be attempted, and can be repeated if not fully effective initially. If aspiration fails, intercostal drain insertion with underwater seal is then recommended.
Secondary pneumothorax: intercostal drainage is agreed first-line management in most symptomatic patients.
Iatrogenic pneumothoraces: in the absence of significant underlying lung disease, may be treated with simple aspiration. Otherwise an intercostal drain should be considered (Box 18.2).
Chest drain management
• In simple pneumothoraces there is no evidence that large tubes (20–24 F) are better than smaller tubes (10–14 F). Large-bore drains are reserved for those with complex pneumothoraces (hydrothoraces/haemothoraces), large air leaks, e.g. bullous lung disease, mechanical ventilation.
• For larger-bore drains, the use of a trocar is not recommended, and the drain should be placed using blunt dissection.
• Intercostal drains should not be removed unless the air leak has resolved (no bubbling) and there is radiographic resolution.
• There is no place for the routine clamping of chest drains.
• Complications of drain insertion include penetration of major organs or vessels and ultrasound guidance, failure of resolution, pleural infection, and surgical emphysema.
• If there is significant surgical emphysema, consider a malpositioned, kinked, or blocked tube, or an air leak too large for the capacity of the drain.
In patients with an ongoing air leak despite a larger-sized drain, high-volume, low-pressure (–10 to –20 cmH2O) suction can be considered in the appropriate setting. In the non-mechanically ventilated patient, a persisting air leak beyond 2–5 days should prompt a chest physician/thoracic surgical involvement (Box 18.3).
Surgical pleurodesis (pleurectomy, abrasive) is the most effective approach to resolve persistent leaks and for preventing recurrence. Chemical pleurodesis with talc slurry is less effective, but may be preferred in those too frail for surgery.
In the critically ill, pneumothoraces are associated with increased morbidity and mortality. The following strategies to reduce risks should be considered.
• Adherence to lung-protective ventilation strategies.
• Ultrasound-guided insertion of central venous catheters.
• A patient with an untreated, closed pneumothorax should not fly owing to the risk of gas expansion and worsening clinical condition.
• If air transport is essential, a functioning intercostal drain is essential.
• Current guidelines recommend a period of 6 weeks following either a definitive surgical procedure or a CXR showing complete resolution before flying.
• In patients with underlying lung disease, without definitive surgery, recurrence risk remains significant up to 1 year later, and alternative transport measures may need to be considered.
The British Thoracic Society recommends specialist referral for anyone with a pneumothorax who takes part in high-risk activities such as diving or frequent flying (pilots, flight crew).
Empyema thoracis (to use full terminology) is a condition in which purulent fluid accumulates in the pleural cavity. An empyema develops when the fluid in the pleural space is infected and progresses from free-flowing fluid to a complex inflammatory collection. It has an associated 1-year mortality of approximately 20–30%. As such, early recognition of pleural fluid and infection is vital in preventing progression, and a high index of suspicion is required in all patients with known risk factors for pleural infection if they are seen to develop a pleural collection.
The incidence of empyema has increased globally over the past few decades. Pleural infection is more common in men, those with a history of alcohol and substance abuse, diabetes mellitus, rheumatoid arthritis, and chronic lung disease. Empyemas may develop in association with the following (although underlying risk factors are not identified in up to one-third of patients):
• Parenchymal lung infections, including lung abscesses.
• Thoracic trauma.
• As a complication of thoracic surgery.
• As a complication of indwelling chest drains or pleural fluid aspiration.
• Oesophageal rupture.
• Spread of infection from the mediastinum.
• Secondary to a bronchopleural fistula.
It is worth noting that the pathogens responsible for pleural infection often differ considerably from those that cause parenchymal lung infection. There is also great geographical variation and differences between community-acquired versus hospital-acquired infections. Infections with anaerobes are more likely to have an insidious onset with less fever and greater weight loss, and are more common following aspiration pneumonia and in patients with poor dental hygiene. Polymicrobial infection is common, with Gram-negative organisms and anaerobes in combination; this is more frequent in elderly patients and those with comorbid disease. Fungal empyemas are rare and mortality rates are high. They tend to be caused by Candida species and are seen in the immunocompromised. In up to 40% of cases a microbiological diagnosis cannot be made, and treatment is empirical, based on local knowledge and the patient’s background. The following organisms can cause infection.
Common organisms in community-acquired pleural infection:
• Streptococcus spp. (~52%): intermedius, pneumoniae, milleri.
• Staphylococcus aureus (11%).
• Gram-negative aerobes (9%): enterobacteriaceae, Escherichia coli.
• Anaerobes (20%): Fusibacterium spp., Bacteroides spp., Peptostreptococcus spp., mixed.
Common organisms in hospital-acquired pleural infection:
• Staphylococci: methicillin-resistant Staphylococcus aureus (MRSA) (25%), aureus (10%).
• Gram-negative aerobes (17%): E. coli, Pseudomonas aeruginosa, Klebsiella spp.
Stages of pleural infection
Classification is according to American Thoracic Society (1962) stages:
1. Exudative (acute) stage: protein-rich pleural fluid remains free-flowing. High neutrophil count, normal glucose, and pH levels. This stage typically lasts for 24–72 h. Drainage of the effusion and appropriate antimicrobial therapy are normally sufficient for treatment.
2. Fibrinopurulent (transitional) stage: increasing fluid viscosity, activation of coagulation factors, and fibroblast activity. Glucose and pH levels start to fall, and septations can develop. This stage typically lasts for 7–10 days.
3. Organizing (chronic) stage: loculated fluid/pus in the pleural space with adherence to the visceral and parietal pleura. This may progress, with the formation of pleural peels in which the pleural layers are indistinguishable. The presence of frank pus denotes an empyema.
History: key points
• Symptoms are non-specific and include: chest pain, fever, sweating, shortness of breath, malaise, loss of appetite, weight loss.
• Ongoing sepsis and raised CRP in patients with pneumonia after ≥3 days of treatment may indicate pleural infection.
• A recent history of pleural intervention, cardiac, or thoracic surgery.
• Blood cultures: all patients should have anaerobic and aerobic blood cultures.
• Imaging of the pleural space is a key element in assessment and management:
○ CXR to detect effusion.
○ Ultrasound may detect small effusions not clearly seen on CXR and may also demonstrate the presence of septations within the pleural fluid collection; echogenic swirling also provides evidence of an exudate; ultrasound guidance also increases the success rate and reduces the complication rate of thoracentesis.
○ Contrast-enhanced CT of the chest can provide additional information regarding pleural enhancement and thickening, the presence of pulmonary abscesses, and the positioning of any indwelling chest drains. Ultrasonography or CT should be used in the placement of drainage catheters.
Diagnostic pleural sampling
All patients with a pleural effusion in association with sepsis or a pneumonic illness require pleural fluid aspiration (or reaspiration if not responding to treatment) under real-time ultrasound guidance. In the case of a septated collection, samples should be obtained from more than one locule. Normally effusions <1 cm on X-ray (or ultrasound) can be safely observed but require repeated imaging. Aspiration should be performed with full aseptic technique. Fluid should be sent, before antibiotic therapy is commenced, for the following:
• Microbiology (in both universal containers and blood culture bottles to improve microbiological yield), including a Gram stain.
• Acid- and alcohol-fast bacilli staining and culture.
• Protein, glucose, lactate dehydrogenase.
• pH. Non-purulent fluid should be collected in a heparinized syringe and measured in a blood gas analyser. Purulent fluid mandates drainage regardless of the pH and can damage analysers.
If left untreated, or with inappropriate or delayed treatment, empyema results in significant morbidity and mortality. The presence of purulent fluid and pleural thickening results in restriction of movement and expansion of the lung. Atelectasis of the underlying lung results in a ventilation–perfusion mismatch, with impaired gas exchange and resulting hypoxia and hypercapnia. Even with treatment, the 30-day postoperative mortality after video-assisted thoracoscopic surgery (VATS) debridement and open decortication has been reported to range between 1.3% and 6.6%.
Complications of empyema
• Empyema necessitans: a swelling appears over the chest wall, which has a positive cough impulse, in communication with the underlying empyema. This resolves with treatment of the underlying empyema.
• Fibrothorax: adhesion of the two layers of pleura, so that the lung is covered by a thick layer of non-expansible fibrous tissue.
• Bronchopleural fistula.
The choice of the appropriate treatment depends on the nature of the underlying disease, stage of pleural infection, and the patient’s comorbidities. The aims of treatment are to control infection, clear infection from and prevent recurrence of infection within the pleural space, and to restore normal pulmonary function. In addition, there is good evidence that optimizing nutrition will improve prognosis. The cornerstones of management are:
• Pleural drainage.
• Deep vein thrombosis prophylaxis (with heparin where possible).
• Early surgical intervention.
• Nutritional supplementation.
Indications for indwelling chest drain
• Pus on aspiration (empyema).
• Organisms either on Gram stain or culture (empyema).
• Non-purulent fluid with pH <7.2 in a patient with suspected infection.
• Loculated effusions.
• Large effusions (for symptomatic relief).
Poor clinical progress during treatment with antibiotics alone should prompt repeat diagnostic aspiration.
Choice and siting of drain
Stage I and II effusions may be managed by antibiotics and chest drain insertion (under ultrasound or CT guidance). Small-bore 12–18 F Seldinger-type chest drains should be sufficient and are well tolerated, but must be flushed regularly (with 30 ml of saline every 6 h) to prevent blockage. Large-bore chest drains block less often but are less well tolerated.
Multiple drains may be needed to manage loculated effusions. Pleural adhesions may form quickly as drainage progresses, leading to the formation of undrained loculations. Frequent imaging with ultrasound or CT is needed to detect such loculae so that additional drainage catheters may be placed if needed.
Fibrinolytics may be used in the treatment of pleural infection, but most recent guidelines suggest that they should not routinely be used. They have been used in an attempt to lyse loculations and thus enhance drainage. A single double-blind RCT demonstrated that tissue plasminogen activator combined with DNase therapy (with the aim of reducing pus/fluid viscosity) did improve fluid drainage in patients with pleural infection. It reduced the frequency of surgical referral and the duration of the hospital stay, but had no effect on adverse events or mortality. Further trials are under way looking at this combination therapy, but at present it should only be considered on a case-by-case basis in patients who fail to respond to antibiotic therapy and conventional drainage and are not suitable or willing to proceed to surgery.
All patients should receive antibiotics as soon as pleural infection is identified, and this should cover community-acquired bacterial pathogens, including anaerobes, pending culture and sensitivity results. Patients with suspected nosocomial infection require broader spectrum antibiotic cover, including cover for MRSA. You should liaise with your microbiology service to ensure best cover. Penicillins, cephalosporins, clindamycin, carbapenems, and metronidazole all show good and similar penetration into the pleural space, in contrast to aminoglycosides, which penetrate the pleural space poorly and are inactivated in low pH environments. There are no controlled trial data to address optimal length of treatment with antibiotics; depending on response, most patients are treated for between 14 and 42 days.
Medical (or ‘local anaesthetic’) thoracoscopy can be used as a drainage procedure and can be performed early in the course of the disease, under sedation with local anaesthesia. It provides a means of mechanically dividing septations and adhesions while placing a chest tube under direct vision in the most suitable location. However, definitive evidence for the routine use of medical thoracoscopy in pleural infection is lacking, and further studies are under way to evaluate its role.
Surgery should be considered in all patients with persistent sepsis despite drainage and antibiotics; however, the decision to refer for surgical intervention remains subjective. Slow radiological clearance of the pleural collection alone, in the absence of ongoing sepsis, should not trigger surgical referral.
VATS debridement is the procedure of choice, and is associated with less pain and shorter recovery period than open thoracotomy. The time frame between onset of symptoms and surgery where VATS debridement can be performed with success has been shown to be between 1 and 2 weeks.
Summary of treatment according to stage
1. Exudative: treat with antibiotics and consider thoracentesis or chest tube drainage.
2. Fibrinopurulent: treat with antibiotics and chest tube drainage; consider intrapleural fibrinolysis on a case-by-case basis, or thoracoscopic (VATS) debridement. VATS is preferred in patients with a good performance status.
3. Organizing: requires formal decortication by thoracotomy to prevent recurrence and restriction.
Haemoptysis, the expectoration of blood from the respiratory tract, is potentially life-threatening. It should be distinguished from haematemesis or bleeding from the nasal–pharyngeal compartment.
Massive haemoptysis is difficult to define and can be a misleading term. Qualitatively, it is the loss of blood at a rate that poses an immediate threat to life. Quantitatively, this may equate to the expectoration of as little as 100 ml of blood in 24 h. In severe cases, volumes in excess of 1000 ml can be produced. Such variation exists for a variety of reasons. The volume of expectorate is not the only factor affecting mortality in haemoptysis. It is also influenced by the rate of blood loss, the ability of the patient to clear blood from the airways, and the extent and severity of any underlying lung disease. Sentinel bleeds may be inconspicuous and the magnitude of bleeding may be underestimated by blood retention within the lower airways. For some patients and medical professionals, volume of haemoptysis can be difficult to quantify and may be subject to interobserver variation. It may then be more useful to use the term ‘life-threatening haemoptysis’, which can be defined as that which results in abnormal gas exchange or haemodynamic instability.
The bronchial circulation is the commonest source of bleeding (90%), followed by the pulmonary (5%) and non-bronchial systemic (5%) circulation. In many cases the culprit vessels are fragile anastomoses that link the bronchial and pulmonary circulation. Pulmonary haemorrhage may be complex if bleeding involves the pleurae.
The commonest causes of haemoptysis in non-Western countries include complications of pulmonary TB (including bronchiectasis and ruptured Rasmussen aneurysms), lung abscesses, and bronchogenic carcinoma. In Western countries, bronchial neoplasms, inflammatory lung disorders (e.g. chronic bronchitis, infections, including fungal lung disease, pulmonary vasculitides, fungal, cystic fibrosis, and non-TB bronchiectasis), thromboembolism, coagulopathies, as well as iatrogenic causes, are encountered. Bleeding pulmonary arteriovenous malformations, ruptured aortic aneurysms, and unusual disorders (e.g. bronchial Kaposi’s sarcoma) make up the rest.
Death due to haemoptysis usually results from asphyxiation (loss of gas exchange surface) rather than exsanguination.
• Plain radiography is readily available and may reveal pulmonary masses and cavities. However, it has a low overall sensitivity in diagnosing haemoptysis or localizing the site of bleeding.
• Contrast-enhanced CT may identify tell-tale aetiological signs (tumour, bronchiectasis, aneurysm) or localize the site of haemorrhage. Even so, it fails to reveal the cause of haemoptysis in up to 10% of cases. CT angiography using multidetector row helical CT enhances the identification of bleeding arteries over conventional CT. It is believed to achieve comparable sensitivity to conventional angiography for distinguishing bleeding from the bronchial and non-bronchial systems.
• Laboratory tests. A full haematology profile, renal and liver biochemistry, inflammatory markers, and clotting panel as well as urinalysis comprise the primary laboratory work-up of any patient with haemoptysis. Additional tests may be ordered to narrow specific diagnoses such as vasculitis, infections, or pulmonary–renal syndromes.
• Bronchoscopy is a widely available and versatile tool. Although its diagnostic accuracy in localizing bleeding sites is reduced by ‘normal’ chest imaging, it enables a range of endobronchial therapies to be administered.
• Selective bronchial angiography, when available, can localize the bleeding site relatively accurately, characterize the nature of the vascular lesion, and guide embolotherapy.
Priorities of clinical management are: 1) securing the upper airway; 2) preserving gas exchange; and 3) replacing lost circulating volume. Administer high-flow oxygen and continuously monitor SpO2, blood pressure, and pulse rate. Secure IV access with large-bore peripheral cannulae; do not waste time attempting central venous cannulation. Infuse colloid or crystalloid fluids unless blood, either matched or Group O-negative, is available.
If immediate tracheal intubation is necessary, use an ETT (size 8–10) large enough to pass a flexible fibreoptic bronchoscope. Positioning the patient with the culprit lung dependent is an intuitive (but unproven) manoeuvre. Enlist anaesthetic or ICU help immediately.
Aggressively identify and treat any coagulopathy. Beware of the patient with coexisting liver or renal disease or those on antithrombotic or antiplatelet agents. The use of the antifibrinolytic tranexamic acid is popular in haemoptysis. One study has demonstrated intravenous tranexamic acid reduces bleeding duration and volume in inpatients with TB. There are also multiple case reports of chronic haemoptysis in cystic fibrosis patients, in which repeated bronchial artery embolizations had been unsuccessful, with subsequent control of bleeding by oral tranexamic acid. As yet, it remains unproven in life-threatening haemoptysis. The role of antitussive agents is also controversial; in theory, they may help to decrease cough-related shear forces within the airways. Use desmopressin and related vasoconstrictors cautiously; their systemic haemodynamic effects may be unacceptable to individuals with coronary artery disease or hypertension. Antimicrobial agents should be targeted against the likely pathogen, either bacterial or fungal.
The use of conservative measures alone in significant haemoptysis is associated with very high mortality. Whilst awaiting bronchoscopic or angiographic intervention, judge whether early cardiothoracic input is necessary.
Rigid versus flexible bronchoscopy
Early bronchoscopy, compared to a deferred procedure, is more likely to identify the site of bleeding. A rigid bronchoscope has a larger luminal calibre and provides superior suction but is more limited in its reach, particularly to the upper lung lobes and peripheral airways, and requires general anaesthesia. In contrast, flexible bronchoscopy affords greater manoeuvrability and can be performed on the ward. In cases where iatrogenic haemoptysis has arisen due to bronchoscopic lesional biopsies, the instrument must be kept advanced distal to the glottis to prevent jeopardizing subsequent airway intubation.
Therapeutic intervention via flexible bronchoscopy
The initial bronchoscopic goal in managing haemoptysis is identification of the bleeding lung segment so that the tip of the bronchoscope can be wedged within it. However, endoscopic visualization of the field can often be obscured by blood. Maintain high-flow suction to remove blood and instil ice-cold saline and adrenaline (1:100 000 dilution) to promote vasoconstriction. Adrenaline may accumulate in the plasma and cause significant cardiovascular effects, such as hypertension and tachyarrhythmias, including ventricular fibrillation. Use 1:100 000 adrenaline in 2-ml aliquots, up to a maximum of 0.6 mg. Cold saline and adrenaline may be useful in mild-to-moderate bleeding after bronchial biopsy or brushing, but is unproven in life-threatening haemoptysis.
Endobronchial antidiuretic hormone derivatives, such as terlipressin, have been shown to be effective in iatrogenic haemoptysis with less cardiovascular sequelae than adrenaline.
Endobronchial tranexamic acid may confer benefit in iatrogenic haemoptysis, either topically or as intratumoral injection prior to endobronchial biopsy. Fibrinogen–thrombin agents may provide a bridging therapy to a more long-term strategy in life-threatening haemoptysis.
The most established manoeuvre to occlude a bleeding pulmonary segment is to produce tamponade using a Fogarty balloon-tip catheter. A small catheter (size 4–7 Fr) may be passed through the inner channel of the bronchoscope for this purpose. A larger catheter will need to be advanced in parallel to the bronchoscope via an in-situ ETT. This method frees the endoscopic channel for suctioning and drug instillation. However, catheter-induced bronchial blockade provides only temporary reprieve and carries recognized ischaemic airway complications. We advise occlusion of the segmental or lobar bronchus for about 2–4 min. The balloon should be gradually deflated to check if fresh bleeding has ceased. The balloon should be reinflated if bleeding persists and further checks made at about 5-min intervals.
If a balloon catheter has already been advanced into the airways prior to placement of an ETT, the bronchoscope will have to be removed before the ETT can be placed. Both single-lumen and double-lumen tubes have been used to protect the bronchial tree in life-threatening haemoptysis. The former isolates the contralateral bronchus by shielding access to the bleeding side. With the latter, the higher (tracheal) cuff acts as a proximal blocker while the longer endobronchial arm is positioned ‘cuffed’ within the contralateral bronchus to ventilate the non-bleeding lung. Secure placement of a double-lumen ETT requires considerable skill.
Future endobronchial therapies
Endobronchial intervention is a rapidly evolving field, with many promising therapeutic options on the horizon. In particular, haemostatic powders have much potential and are already used in the treatment of surgical wounds, epistaxis, and upper gastrointestinal bleeding. These powders target sites of bleeding and encourage haemostasis by barrier formation and local concentration of clotting factors. They are ideal for endoscopic treatment, and could easily be adapted for application via a flexible bronchoscope. Also of note is a method of topical tamponade with oxidized regenerated cellulose mesh. This is a sterile fabric that can be introduced bronchoscopically and, in early studies, has been shown to be 98% effective in massive haemoptysis after endobronchial wedging, cold saline, and adrenaline had been unsuccessful.
Successful use of recombinant factor VIIa to promote haemostasis has been described in case reports of patients with significant haemoptysis. However, its efficacy has yet to be confirmed in a controlled trial. Laser photocoagulation and radiotherapy have no role in the emergency treatment of haemoptysis.
Percutaneous angiography and bronchial artery embolisation
Selective bronchial angiography may provide vital diagnostic information in the preoperative setting or immediately prior to therapeutic embolotherapy. In skilled hands, bronchial artery embolization is highly successful in controlling life-threatening haemoptysis in patients unsuitable for surgery. Typical angiographic findings in large-volume haemoptysis include vessel tortuosity, hypertrophy, hypervascularity, aneurysmal dilatation, and arteriovenous shunting. Dye extravasation is an unusual finding. A variety of embolization materials are employed, including polyvinyl alcohol foam, absorbable gelatin particles, and stainless steel platinum coils.
Bronchial artery embolization is not without risk; recognized complications range from transient visceral ischaemia (e.g. chest pain or dysphagia) to catastrophic spinal infarction.
Surgical management of haemoptysis
Emergency surgery for acute massive haemoptysis carries a significant risk of death of up to 30%. Indications for emergency thoracotomy have decreased with advances in bronchoscopic and radiological intervention. Currently, surgery is employed mainly in the event of failure of arteriography or recurrence of haemoptysis despite bronchial artery embolization. However, it also remains the management of choice for haemoptysis resulting from leaking aortic anerysms, traumatic chest injuries, pulmonary vessel haemorrhage, and bleeding from a mycetoma unsuccessfully controlled by other means.
Smoke inhalation injury occurs in about one-third of patients with major burns and in about two-thirds of those with facial burns, and contributes significantly to the mortality of burns patients. It is the most frequent cause of death at the scene of a fire. Injury to the airway and tracheobronchial tree may also result from inhalation of chemicals (such as chlorine gas), drugs, and biological weapons. Systemic disturbances are common, but depend on the nature and toxicity of the inhaled substance. Recent advances in burns care have significantly improved patient outcome, but they have not benefited the patients with burns and an inhalational injury to the same degree. Therefore, the optimal management of patients with an inhalational injury is of great importance.
Overall, pulmonary injury results from damage due to heat, hypoxia, and toxins (local and systemic). The components of smoke (heat, particulate matter, toxins, and respiratory irritants) are responsible for the triggering of an acute inflammatory process that affects the mucosal surfaces of the airway and the lung parenchyma.
Initially, there is an influx of neutrophils, formation of oxygen free radicals, macrophage activation, and production of inflammatory mediators. This results in an increase in pulmonary capillary permeability and transpulmonary fluid flux, with a consequent increase in extravascular lung water and higher pulmonary shunt fraction. In addition, injury to type II pneumocytes results in a reduction of surfactant production and hyaline membranes may form on the denuded alveolar basement membranes. Upregulation of NO has also been implicated in the pathogenesis of associated lung injury.
In some patients this exudative phase may be followed by uncomplicated repair and resolution; however, others may develop a fibrotic phase. During this fibrosing alveolitis, neoangiogenesis and increased collagen deposition is seen.
Exposure of the mucous lining of the airway and tracheobronchial tree to extreme heat results in immediate erythema, oedema, and ulceration. Airway compromise due to oedema is a significant risk. Thermal damage is usually limited to the supraglottic region owing to the heat exchanging capacity of the upper airway. Distal thermal damage is rare, but can result from inhalation of superheated particles or saturated gases. Dry gases have a lower specific heat capacity than saturated gases and consequently have less potential to cause injury.
Toxins causing direct damage to the epithelium of the airways include sulfur dioxide, nitrogen dioxide, chlorine, and ammonia. Their effects result from pH or free radical damage. Distal carriage can occur in the presence of carbon particles. Increased alveolar capillary permeability and lung water contribute to decreased lung compliance. Epithelial cast formation and sloughing, mucociliary dysfunction, and oedema result in increased airway resistance, airway obstruction, atelectasis and predisposition to bacterial overgrowth, and the development of pneumonia. Ventilation–perfusion mismatch with increased pulmonary shunt results.
Systemic toxins include the asphyxiants carbon monoxide, hydrogen cyanide, and hydrogen sulfide. These bind to mitochondrial cytochromes, causing disruption of the electron transport chain. Carbon monoxide has a higher affinity for haemoglobin than oxygen, preventing binding of the latter and impairing oxygen carriage. Other systemic toxins include hydrocarbons, organophosphates, and metal fumes.
Particulates and irritants
Particulate matter is a major contributor to the inflammatory process that occurs with an inhalational injury. Carbonaceous particles that can reach the distal lung parenchyma can be saturated with toxins and irritants, which will vary with the material that has been burned. It is important to remember that compounds that are poorly water-soluble (e.g. the oxides of nitrogen) may affect the mucosa more deeply and consequently may be the cause of delayed inhalational injury.
Presentation will vary according to the severity and type of injury and presence or absence of cutaneous burn. History (e.g. fire in enclosed space) is essential in identifying the risks of carbon monoxide and cyanide poisoning, significant inhalation injury, and airway compromise. Signs and symptoms can develop up to 36 h after inhalation injury.
Initial assessment should take the form of a trauma primary survey. The presence or absence of cutaneous burns does not predict the potential for airway or respiratory compromise. Standard monitoring should be applied and intravenous access be established.
Obstruction or risk of obstruction must always be considered early while administering high-flow humidified oxygen. It is a clinical diagnosis; blood gas analysis and oximetry should not be relied upon. Decreased oxygen saturation is a late and preterminal sign of airway and breathing compromise.
The strongest clinical correlates with requirement for tracheal intubation are: soot in the oral cavity, facial burns, body burns, and fibreoptic laryngoscopic findings of oedema of either the true or false vocal folds. The classic symptoms of inhalation injury: stridor, hoarseness, drooling, and dysphagia correlate poorly with the need for tracheal intubation. Maximal oedema occurs between 8 and 36 h after the initial insult and may persist for up to 4 days; it is exaggerated by excessive fluid resuscitation. Paradoxical (abdominal) breathing pattern, tracheal tug, and intercostal muscle recession with inability to speak are signs of imminent airway obstruction.
Respiratory distress due to inhalation injury usually takes several hours to develop. If evident on presentation, airway compromise must be excluded. Clinical signs include tachypnoea, intercostal recession, accessory muscle use, wheeze, and bronchorrhoea. Soot or burn discoloration and the potential presence of carboxyhaemoglobin render cyanosis an unreliable sign. Hypoxic pulmonary vasoconstriction combined with increased thromboxane release following smoke inhalation may result in pulmonary hypertension and right ventricular dysfunction.
Vital signs should be monitored continuously during the assessment and initial management phase. Pulse oximetry can give erroneously high readings in the presence of significant carboxyhaemoglobin.
ABG analysis with co-oximetry is essential to assess carboxyhaemoglobin levels.
Blood should be drawn for cyanide levels; however, the results may take several days to be ascertained. Cyanide toxicity should be suspected and treated in patients with persistent high blood lactate levels, acidaemia, high mixed venous oxygen saturation, low oxygen extraction ratio, and deteriorating neurological and cardiac function despite appropriate resuscitation.
Corrected anion gap and osmolar gap should be calculated if acidaemia persists. Toxicology screen should be considered, particularly in patients with reduced or inconsistent neurological levels.
Bronchoscopic examination is useful in assessing the tracheobronchial tree of patients who are stable and have undergone endotracheal intubation. It can be combined with therapeutic lavage.
CXR signs may lag behind the clinical course of the patient. A normal chest radiograph does not exclude significant, early inhalation injury.
Attention to airway, breathing, and circulatory abnormalities forms the central tenet of initial management.
Airway swelling and obstruction is progressive, and may be exacerbated during fluid resuscitation, emphasizing the need for constant reassessment. High-flow humidified oxygen should be administered to all patients in the first instance. If airway compromise is anticipated, expert endotracheal intubation should be performed with prior preparation for difficult or failed intubation. Large diameter uncut tracheal tubes should be used (the former to facilitate bronchoscopic therapies).
Respiratory management should focus on oxygen delivery. Inhalation injury commonly triggers pulmonary inflammation and ARDS; however, this may develop insidiously over a period of hours or days. If mechanical ventilation is required, standard recruitment and lung protection measures should be employed. Early bronchoscopy is recommended to record level and degree of injury. Lavage should be performed if pulmonary contamination or cast formation are evident; however, consideration should be given to the fact that excessive saline lavage may induce lung injury. If severe ARDS occurs, then more invasive supportive therapies such as ECMO, or arteriovenous CO2 removal can be considered, but these are novel techniques with little evidence to support them.
Regular administration of aerosolized bronchodilators should be considered. Nebulized heparin and acetylcysteine have been used to reduce cast formation, distal airway obstruction, and atelectasis.
Antibiotic and steroid therapies have no proven prophylactic role but may be required in specific situations. Pneumonia is the most common cause of death in hospitalized patients suffering from inhalation injury and should be treated promptly.
Carboxyhaemoglobin levels >10% should be treated with 100% inspired oxygen therapy. The half-life of carboxyhaemoglobin is reduced from 240 min at an FiO2 of 21% to ~80 min with an FiO2 of 100%. If immediately available, hyperbaric therapy may be considered in patients with carboxyhaemoglobin >40%, or 20% if pregnant and in patients who have had lowered conscious level from no other cause; however, long-distance transfers risk critical deterioration owing to unidentified injuries or inadequate treatment en route and are not advised.
Suspicion of cyanide poisoning (see section on ‘Specific investigations’) should prompt empiric treatment with the cyanide-binding agent hydroxycobalamin; this has an acceptable safety profile in the absence of definitive diagnosis. Other agents may be used if cyanide toxicity is proven: sodium thiosulfate acts slowly by catalysing the metabolism of cyanide; sodium nitrite reduces cyanide binding by oxidation of haemoglobin to methaemoglobin (methaemoglobin levels of ~40% should be targeted). Dicobalt edetate is another available binding agent but may induce cardiac arrhythmias and instability if used in the absence of cyanide poisoning.
Cardiovascular support primarily involves fluid resuscitation. This can be extremely difficult to assess, particularly if large burns coexist. Widespread increases in capillary permeability result in fluid redistribution into the interstitium, including that of the lung and airway. Patients with major burns and inhalation injury require far greater fluid resuscitation than those with either injury alone. Limitation of fluid resuscitation in victims of smoke inhalation has not been supported in clinical trials. Crystalloid resuscitation for the first 24 h is based on historic evidence, but the use of cardiac output monitoring can help to guide the volumes given.
ARDS is a trigger of systemic inflammatory response syndrome and multiple organ dysfunction. Inotrope and vasopressor therapy may be required. Adrenal insufficiency should be considered in patients who are refractory to vasopressor therapy, and replacement therapy commenced if appropriate. Improvement in cardiac output and blood pressure may enhance oxygenation through improved lung perfusion and reduced intrapulmonary shunt.
Longer-term management considerations
Chest physiotherapy remains widely accepted management despite a lack of evidence to support it. Tracheostomy should be considered in patients requiring long-term MV or pulmonary toilet.
ARDS from any cause is associated with increased resting energy expenditure, dramatically so if burns are also present. Careful attention to nutritional management should be considered at an early stage and reviewed continuously.
Therapies employed in the management of long-term critically ill and mechanically ventilated patients should be considered. Examples include the use of prophylaxis against venous thromboembolism and gastrointestinal stress ulceration.
Long-term pulmonary sequalae following inhalation injury seldom occur. Cases of bronchiectasis, interstitial fibrosis, and tracheal stenosis have, however, been reported, but the exact aetiology is unclear. Identification at bronchoscopy of severe inhalation injury and the requirement for MV have been linked to increased mortality in this patient group.
PE is defined as the obstruction of the pulmonary artery and/or branches by a substance that has travelled in the bloodstream from somewhere else in the body. When this substance is a blood clot it is called pulmonary thromboembolism (PTE). PTE has the potential to obstruct bloodflow and produce significant cardiopulmonary dysfunction and may lead to hypoxaemia, shock, and death.
Most PTEs come from the lower extremities, although up to 50% of patients with PTE have no evidence of lower extremity or deep vein thrombosis (DVT). Other sources of DVT include the pelvis, inferior vena cava, and upper extremity veins. Typically, several emboli migrate and wedge into the pulmonary artery branches. Lower lobe circulation is more frequently affected. This usually leads to an alteration of the ventilation/perfusion ratio, impairing gas exchange and producing hypoxaemia. With more and distal emboli, pulmonary infarction can occur with significant inflammatory reaction. With large emboli, significant obstruction of the vascular flow leads to increased pulmonary vascular resistance followed by a diminished stroke volume and cardiac output.
Risk factors for PTE are identical to those for DVT (Box 18.4) and may be either acquired or inherited.
Often critically ill patients have several risk factors (acquired and/or inherited) and face an even greater risk for DVT and PTE.
The most frequent symptom of PTE is new-onset dyspnoea at rest or with exertion. It has been reported in more than two-thirds of patients. Chest pain and non-productive cough may be present. Haemoptysis is rare, associated with pulmonary infarction, and typically presents as a minimal amount of blood-tinged sputum rather than frank blood.
The classic triad of chest pain, haemoptysis, and dyspnoea is present in <20% of patients. Of patients with PE, 97% have at least one of the following: pleuritic chest pain, dyspnoea, or respiratory rate >20/min.
Tachypnoea (50%) and tachycardia (25%) are the most common signs. Clinical evidence of acute pulmonary hypertension such as an accentuated pulmonary S2 is present in about 20% of patients with PTE. Chest auscultation is abnormal in >30% of patients, with crackles and decreased breath sounds common. A low-grade fever may be present. It is rarely more than 101.0°F.
Although hypoxaemia is a common finding in patients with PE, a normal ABG, however, does not rule it out. In patients with no prior cardiopulmonary disease, totally normal ABGs are found in more than 25% of patients with documented PE.
The underlying predominant mechanism is a low ventilation/perfusion ratio. The dead space in large PE may lead to a rise in the PaCO2, which translates into a decrease of end-tidal CO2.
End-tidal CO2 monitoring could be a useful tool to monitor for successful thrombolysis in the critical care setting.
The most common findings on chest radiograph include pulmonary infiltrate, atelectasis, pleural effusion, and cardiomegaly. Less common signs include Westermark sign (dilatation of pulmonary artery proximal to the emboli with more distal hypoperfusion in a segmental distribution, Hampton’s hump (a pleural-based wedge-shaped infiltrate), and elevated hemidiaphragm.
ECG and echocardiogram
ECG findings, including tachycardia and non-specific ST-T elevation, lack specificity, with more specific findings being signs of right ventricle strain such as P pulmonale, S1Q3T3, right bundle branch block, or right axis deviation.
Echocardiogram signs of acute pulmonary artery hypertension include right heart dilation, tricuspid regurgitation, pulmonary artery dilation, loss of respiratory variation in vena cava diameter, and interventricular septum bulge into the left ventricle. Acute right ventricular dilation with hypokinesis sparing the apex, McConnell’s sign, is a characteristic finding. One of the main advantages of echocardiogram is its ease of use at bedside in unstable and difficult-to-transport patients.
Of note, the healthy right ventricle cannot generate mean pulmonary artery pressure >40 mmHg in an acute situation like PE. The presence of higher pressure reflects pre-existing pulmonary hypertension.
The D-dimer assay, when not elevated, is very useful in identifying patients with low likelihood of PTE. This is especially true when combined with ‘PTE likely’ using standardized scoring systems. It is important to recognize that D-dimer levels are elevated in patients with underlying conditions such as coexisting inflammation, infection, pregnancy, renal dysfunction malignancy, and advancing age.
Ventilation/perfusion scan (V/Q scan) and CT angiography
With the availability of multidetector CT pulmonary angiogram (CTPA), the use of V/Q scan has been reserved for patients with contraindications for CTPA, including pregnancy and abnormal renal function. It is a sensitive test that lacks specificity. Diagnostic utility is increased in patients with normal chest radiograph.
Detection of PE has significantly increased with the advancement of multidetector CT scan, which can detect small clots in small arteries 2–3 mm in diameter. The degree of detection has improved to a point where one would question the clinical significance of very small clots and the potential complications of anticoagulation.
Lower extremities duplex ultrasound
Lower extremities ultrasound is often useful in the evaluation for possible PTE as it may show the presence of DVT that supports the diagnosis and call for anticoagulation. It is particularly useful when unable to perform other imaging modalities or when other imaging modalities are inconclusive. A negative ultrasound does not rule out PTE.
Invasive pulmonary angiography
Although still considered the gold standard, with the advancement of CTPA, invasive pulmonary angiography is rarely used today for diagnostic purposes. It is invasive when compared to other diagnostic modalities. It is used in conjunction with therapeutic interventions such as catheter-directed thrombectomy or thrombolysis.
After diagnosis, the initial approach should be directed to assure and restore adequate oxygenation and haemodynamic stability, followed by initiation of anticoagulation.
In haemodynamically unstable patients, initiation of inotropes/vasopressors (noradrenaline with the potential addition of dobutamine) is indicated. Although an occasional patient might benefit from intravenous fluids, fluid administration can produce deleterious effects on left ventricular function as a result of right ventricular dilation and interventricular shift toward the left ventricle, causing decreased left ventricular compliance and lowered cardiac output.
The initiation of anticoagulation should not be delayed during evaluation of higher risk patients and the consideration of more aggressive therapy such as thrombolysis. Thrombolytic therapy is indicated in the presence of vasopressor requirement and no contraindications. The initiation of thrombolytic therapy should be based on fairly convincing evidence of PE, including bedside echocardiogram in patients who cannot be transported for CTPA. Rapid or bolus infusion could be considered in critically ill patients with a rapidly deteriorating clinical course.
Use of a low-dose thrombolytic can be considered in patients with massive PE at relative increased risk of bleeding.
Thrombolysis failure, which is defined as persistent right ventricular dysfunction and haemodynamic instability following thrombolysis, is a consideration for catheter-directed thrombolysis, surgical embolectomy, or pulmonary artery catheter-directed therapy. There are not enough data to support routine use of thrombolytics in PTE complicated by right ventricular dysfunction without haemodynamic compromise, although it may be appropriate in some scenarios.
Low-molecular weight heparin (LMWH) is the anticoagulant of choice in treating PTE. While LWMH is reserved for haemodynamically stable patients, unfractionated heparin (UFH) is preferred in haemodynamically unstable patients with potential need for invasive procedures. Intermittent injection of heparin is associated with a higher rate of bleeding than heparin infusion; therefore it is not recommended. Fondaparinux has at least equal efficacy to LMWH and once-daily convenient dosing, but should not be used in renal insufficiency. Platelet count should be monitored while on LMWH or UFH for early detection of heparin-induced thrombocytopaenia.
Warfarin is indicated for the long-term treatment of acute PTE. It is often started within 24 h after the initiation of the heparin therapy. It should be continued in conjunction with heparin until the international normalized ratio (INR) reaches a therapeutic level of 2–3 with a minimal 2 days of warfarin dosing. Heparin should be given for at least 4 days regardless of therapeutic INR. Warfarin is highly effective in preventing recurrent PE. Warfarin therapy requires frequent long-term monitoring of INR level, which may be affected by factors such as food intake or drug–drug interactions.
Direct factor Xa and thrombin inhibitors have recently been introduced for the long-term treatment of acute PE, with two advantages: the rapid onset of action within 2–3 h and lack of a requirement for blood monitoring tests. Drawbacks are the lack of reversibility in case of major or minor bleeding and decreased clearance in patients with abnormal renal function.
Inferior vena cava filter insertion is indicated when anticoagulation is contraindicated or in patients who qualify for thrombolytic therapy but have contraindications. Removable filters are preferred. Prophylactic filters should also be considered in some patients at high risk for PE, such as spine surgery or multisystem trauma.
Prophylaxis and prevention
PTE and DVT are common during inpatient stays, especially in the critical care setting. All critical care patients are considered at high risk. Without prophylaxis, DVT is reported in a high percentage of ICU patients and PTE is the third leading hospital-acquired cause of death after the first day of admission. PTE is considered the most preventable cause of death during a hospital stay. When admitted to the ICU, prophylaxis should be started within 24 h of admission and pharmacological prophylaxis should be prescribed unless contraindicated. Mechanical prophylaxis should be used when anticoagulants are contraindicated and in conjunction with pharmacological therapy in patients at very high risk (including severe sepsis). LMWH is the pharmacological agent of choice and monitoring factor Xa levels is not required.
The major risk factors for PTE include right-sided heart failure, the postoperative period, prolonged bedrest, long-distance travel, trauma, advanced malignancy, pregnancy, the postpartum period, birth control pills, previous DVT, and a hypercoagulable state.
Community-acquired pneumonia (CAP) has an overall incidence of 10–15 per 1000 adults and this incidence has increased steadily over the past decade. This can only partly be explained by an ageing population.
It is characterized by cough, tachypnoea, sputum production, focal chest signs, and evidence of systemic sepsis. A chest radiograph will show shadowing in one or more lung segments. About 30% of such patients are admitted to hospital and, of these, 5–10% require ICU admission. Mortality in this group in the UK is over 30%. We will discuss severe CAP in adults and will not include patients with hospital-acquired pneumonia, those with acute exacerbations of COPD, or patients with severe immunosuppression.
CAP typically presents with fever, respiratory symptoms (cough, sputum, and shortness of breath), and crackles or bronchial breathing on chest examination. Pleuritic chest pain occurs in a third of presentations. Confusion is common in the elderly and may be the only symptom.
An infiltrate on CXR or other imaging modality is required for diagnosis, although these can be hard to interpret if there is pre-existing lung disease.
CT scanning has higher sensitivity for diagnosis but is not routinely used due to expense, increased radiation exposure, and lack of evidence that it improves outcomes.
The main serological abnormalities are leukocytosis (15–30 000/mm3) with a leftward shift and CRP elevation (>100 mg/l). When present, leukopaenia is a prognostically poor sign.
Treatment directed at a causative pathogen is ideal but practically is rarely achievable with current diagnostic tests. Many studies, even with rigorous testing, only identify a pathogen in 20–25% of cases.
Of patients admitted to ICU or HDU in Europe, the most common identified aetiological agents are:
• Streptococcus pneumoniae, 28%.
• Staphylococcus aureus, 6%.
• Legionella pneumophila, 6%.
• Haemophilus influenzae, 5%.
• Pseudomonas aeruginosa, 5%.
In up to two-thirds of cases no organism is isolated. It is likely with the increasing availability of rapid polymerase chain reaction (PCR) diagnostics a higher incidence of viral pathogens will be identified.
Identification of influenza with PCR testing is important for public health reporting purposes and for oseltamivir treatment if it is a susceptible strain. Staphylococcus aureus pneumonia is an occasional, often lethal, complication of influenza.
The mortality rate of patients with positive and negative microbiology investigations remains similar. Clinical and radiological features are not helpful in distinguishing between different aetiologies.
In severe CAP, initial management should follow standard ABCDE assessment. The airway should be assessed, and high-flow oxygen administered to ensure an oxygen saturation (SaO2) >92%. Signs of respiratory distress, respiratory rate, poor perfusion, shock, focal chest signs, and level of consciousness are noted. IV access is established, baseline investigations performed, and IV antibiotics commenced (see section on ‘Antibiotic therapy’). The CURB-65 score is quick and easy to do and is recommended by the British Thoracic Society. SMART-COP scoring may be more predictive of the need for ICU admission.
1 Adapted from Thorax, 58, Lim WS, van der Eerden MM, Laing R, et al, Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study, pp. 377–382. Copyright © 2003, BMJ Publishing Group Ltd and the British Thoracic Society.
The CURB-65 score is a 6-point scale (0–5) for assessing severity and risk of death in CAP. One point is given to each of:1
• Confusion: new-onset confusion (mini-mental test ≤8).
• Urea: raised urea >7 mmol/l.
• Respiratory rate: ≥30 breaths/min.
• Blood pressure: systolic blood pressure <90 mmHg and/or diastolic blood pressure ≤60 mmHg.
• 65: age ≥65 years.
Mortality rates are: score 0, 0.7%; score 1, 3.2%; score 2, 13%; score 3, 17%; score 4, 41.5%; score 5, 57%. Patients with a score of ≥3 require urgent hospital admission and senior assessment for ICU admission.
2 Reproduced from Clinical Infectious Diseases,47,3, Patrick G. P. Charles, Rory Wolfe, Michael Whitby, et al., SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia, pp. 375–384. Copyright © 2008, Oxford University Press.
SMART-COP is designed to predict the need for intensive care interventions (ventilation and/or inotropes). It is calculated as follows:2
• Systolic blood pressure <90 mmHg, 2 points.
• Multilobar involvement, 1 point.
• Albumin <30 mg/dl, 1 point.
• Respiratory rate ≥25 (50 years or less) or ≥30 (over 50 years), 1 point.
• Tachycardia >125 bpm, 1 point.
• Confusion (new), 1 point.
• Oxygen low pO2 <9.3 kPa (50 years or less) or <8 kPa (over 50 years), 2 points.
• pH <7.35, 2 points.
Patients with a score of 0–2 have a low risk of requiring ventilation or inotropes. Those scoring 3–4 have a moderate risk (1 in 8). Patients with scores of 6–7 are at high risk (one-third) and those over 7 are at very high risk (two-thirds).
Although these scores can be useful to aid clinical judgement, including an assessment of any comorbidities is essential in determining severity.
All patients with severe pneumonia require a CXR, FBC, U&Es, LFTs, CRP, blood gas analysis, and lactate.
Microbiological investigations required are:
• Blood cultures, ideally before the first dose of antibiotic, although the latter should not be delayed. They are positive in 10–20%.
• Urine for pneumococcal C polysaccharide antigen and Legionella antigen testing. This is 95% specific and 80% sensitive, and is especially useful if antibiotics have been given prior to cultures being taken. Positive Legionella antigen testing requires follow-up sputum culture to allow typing.
• Influenza testing (PCR on sputum or throat swab) if in season.
• PCR on respiratory samples is the preferred method for diagnosis of viral pneumonia and atypical pathogens.
CAP which requires ICU is a severe illness with a high mortality. Treatment consists of early IV administration of appropriate antibiotics within 6 h (within 1 h in the presence of shock) and supportive care. Patients may require ICU for the support of the respiratory system, the circulation, and other organ systems.
In all patient groups S. pneumoniae is the most common pathogen in severe CAP. Unlike meningitis, penicillin resistance of S. pneumoniae is not an issue in the treatment of pneumonia, since tissue levels approximate blood levels.
• The National Institute for Health and Care Excellence recommends that initial antibiotic therapy should consist of co-amoxiclav 1.2 g 8-hourly IV, or a second- or third-generation cephalosporin, plus a macrolide, usually clarithromycin 500 mg 12-hourly IV or via the enteral route.
• In patients with true anaphylactic reactions to β-lactams, discuss with the local microbiology department. Levofloxacin 500 mg 12-hourly IV is one option. This can also be added if there is a poor response to initial therapy.
• In confirmed Legionella, preferred treatment is a fluoroquinolone (e.g. levofloxacin) combined with a macrolide (beware of QT prolongation) or rifampicin.
• Treatment with antibiotics should continue for 5–7 days, extending to 14 days in cases of staphylococci or Gram- negative enteric bacilli.
• Panton–Valentine leukocidin-producing Staphylococcus aureus produces a severe necrotizing pneumonia with cavitation on lung imaging and multiorgan failure. If suspected, linezolid 600 mg 12-hourly IV, clindamycin 1.2 g 6-hourly, and rifampicin 600 mg 12-hourly are added to the initial therapy.
• MRSA pneumonia should be suspected if the patient has previously had MRSA infections or is colonized. The local microbiology department should be notified and treatment with linezolid commenced (600 mg 12-hourly IV).
• Multidrug resistant (MDR) organisms are a rare cause of CAP. Pseudomonas is prevalent in patients with bronchiectasis or structural lung disease who have been exposed to multiple courses of antibiotics. MDR organisms are more likely in non-ambulant or tube-fed patients who have been exposed to antibiotics or hospitalized for more than 48 h within the previous 90 days. Local microbiological knowledge is essential to guide empirical antibiotic therapy in such cases.
• Middle East respiratory syndrome coronavirus emerged as a cause of severe pneumonia in Saudi Arabia in 2012. PCR testing is advised with a suggestive travel history.
• NIV can produce a transient improvement in oxygen saturation, but >50% of patients subsequently require intubation. If NIV or nasal high-flow oxygen are initiated for CAP it should be in an intensive care environment, where invasive ventilation can be undertaken rapidly. There has been concern that use of NIV or nasal high-flow oxygen may delay intubation and worsen outcome.
• Invasive ventilation should aim at ensuring a safe level of oxygenation (PaO2 >8 kPa) while minimizing pulmonary barotrauma and volutrauma. Ventilation should follow guidelines for ARDS. However, in severe lobar pneumonia, much of the lung may not be recruitable. High levels of PEEP can damage normal alveoli and worsen shunt.
• Prone positioning and ECMO may be considered in selected cases.
Septic shock worsens the prognosis in CAP, and should be treated with optimal volume loading and inotropes (noradrenaline ± dobutamine). There is now no evidence that early goal-directed therapy improves outcome over normal clinical care. Fluids should be restricted following initial resuscitation to minimize lung water.
Parapneumonic effusions and lung abscess
Up to 50% of patients with bacterial CAP develop parapneumonic effusions.
• Effusions should be tapped under ultrasound control. The appearance is noted, and microscopy and culture requested. If the fluid is clear, the pH is measured anaerobically in a blood gas syringe.
• A complicated parapneumonic effusion is defined as clear fluid with a pH <7.2. In empyema, the fluid is cloudy; frank pus or organisms are present on Gram stain.
• Both require effective pulmonary drainage and, in the case of an empyema, a surgical opinion.
Lung abscesses are more common in debilitated patients, alcoholics, and following aspiration. A variety of organisms may be responsible. Treatment consists of prolonged antibiotics and a surgical opinion.
• Patients with S. aureus or S. pneumoniae may develop metastatic infections, including meningitis, endocarditis, and septic arthritis.
• Legionella can produce a variety of complications, including encephalitis, pericarditis, pancreatitis, polyarthropathy, hyponatraemia, abnormal liver function, thrombocytopaenia, diarrhoea, and renal failure.
Definition and epidemiology
Hospital-acquired pneumonia (HAP) is defined as a pneumonia beginning more than 48 h after hospital admission. Data from the EPIC II study suggest the respiratory tract as the focus of 64% of all ICU nosocomial infections. Its incidence is between 5 and 15 episodes per 1000 hospital admissions. More than 80% of HAP episodes in ICU are related to MV, e.g. VAP. HAP mortality in ICU is highly variable and attributable mortality is controversial, although this condition prolongs MV and ICU length of stay.
For HAP occurrence there must be the entry of pathogens into the lower respiratory tract, followed by colonization, then overwhelming of the host’s defences. The balance among pathogen virulence, host defence, and bacterial burden (associated with volume of aspiration) is the most important factor on HAP/VAP development. Important mechanisms associated on pathogenesis are:
• Aspiration of oropharyngeal pathogens and leakage of bacteria around the cuff of the tracheal tube (>90% of episodes).
• Colonization of tracheal tube (biofilm).
• Condensate on ventilator circuits, nebulizer, and humidifiers.
• Inhalation or direct inoculation of pathogens into the lower airway.
• Haematogenous spread (uncommon).
The risk factors for HAP include patient characteristics and infection control-related problems. The main risk factor is intubation and MV.
Patient-related risk factors include:
• Severe acute or chronic illness.
• Advanced age.
• Respiratory failure.
An important issue in HAP is the increasing rates of HAP episodes due to MDR pathogens, especially in ICUs. Risk factors associated with MDR HAP are:
• Antimicrobial therapy in last 90 days.
• Current hospitalization >5 days.
• Immunosuppressive disease or therapy.
• Hospitalization for >2 days in the preceding 90 days.
• Residence on nursing home.
• Chronic dialysis.
• Family member with MDR infection.
The most common pathogens include aerobic Gram-negative bacilli (P. aeruginosa, E. coli, K. pneumoniae, and Acinetobacter baumannii). Increasing prevalence of MDR Enterobacteriaceae, mainly carbapenem-resistant strains, is a current therapeutic challenge. Gram-positive cocci S. aureus, particularly MRSA, are a very important issue in most ICUs. Polymicrobial episodes are very common.
Several factors, such as age, diabetes mellitus, head trauma and coma, local flora, and previous exposure to antibiotics, may increase the frequency of specific pathogens.
In VAP patients, a very important issue is the time of onset of pneumonia (Table 18.9).
Table 18.9 Common pathogens characterized by time of pneumonia onset
Early-onset pneumonia (<5 days)
Late-onset pneumonia (>5 days)
Meticillin-sensitive S. aureus
HAP episodes must be considered preventable until proven otherwise. Prevention of HAP/VAP episodes constitutes a cornerstone on optimal clinical practice on ICU. The application of a bundle of evidence-based interventions (care bundle) has been demonstrated to reduce the pneumonia incidence in several studies. The main evidence-based interventions are:
• Daily interruption of sedation.
• Reduce duration of intubation and of MV through an improvement in sedation management and early weaning.
• Semirecumbent position (30–45°).
• Control endotracheal cuff pressure at least every 24 h.
• Oral hygiene with chlorhexidine.
• Hand hygiene.
• Appropriatelly educated and trained staff.
• Avoid intubation and reintubation.
• No ventilatory circuit tube changes unless specifically indicated.
• Infection control measures.
HAP diagnosis should be suspected in every patient with a new or progressive radiographic infiltrate with purulent respiratory secretions plus new onset of fever, leukocytosis, or hypoxaemia.
Initial clinical approach should include:
• Comprehensive medical history, looking for risk factors associated with specific pathogens.
• Chest radiograph, evaluating the presence of complications such as pleural effusion.
• Arterial oxygenation/respiratory rate assessment.
• Assess the presence of organ dysfunction/evaluate severity scores.
• Administration of antibiotics should not be delayed in pneumonia management because inadequate treatment increases mortality.
• Samples of lower respiratory tract secretions should be obtained (see section on ‘Microbiological diagnosis’).
Quantitative cultures should be obtained by non-invasive (endotracheal aspirate) or invasive techniques (bronchoscopy-guided bronchoalveolar lavage or protected specimen brushings). The choice of method depends on local expertise, availability, and cost. New molecular and PCR-based methods will improve our ability to detect pathogens and guide therapy promptly.
The therapeutic approach to HAP/VAP must be patient-based and institution-specific. Empirical treatment choice must be guided by the characteristics of patients, the local pattern of antimicrobial resistance, and by direct staining of respiratory samples.
Initial empiric therapy for HAP/VAP according to time to onset and presence of risk factors is shown in Table 18.10.
Table 18.10 Empiric therapy based on time of pneumonia onset and likely pathogens
Early–onset without risk factors
Meticillin-sensitive S. aureus,
Cephalosporin third/fourth generation or
Late-onset or with risk factors for MDR pathogen
MDR and carbapenem-resistant Gram-negative bacteria
Antipseudomonal cephalosporin or
antipseudomonal carbapenem or
polymyxin B or E (endovenous or inhaled)
quinolone or aminoglycoside or tigecycline
Linezolid or vancomycin or anti-MRSA cephalosporins
• Empirical antibiotic choice driven by local microbiological data:
• Data demonstrate an important variability in pathogens in different centres and different ICUs, proving to be fundamental in knowing local flora and susceptibility data to optimize empirical antibiotic treatment appropriateness.
• Prompt initiation of appropriate antimicrobial treatment:
• An appropriate initial antibiotic treatment is associated with better outcomes in HAP/VAP patients. The shorter the delay in starting empirical treatment, better the impact on prognosis, length of stay, and cost.
• Appropriateness of antimicrobial treatment (dose, pharmacokinetics/dynamics considerations, tissue penetration):
• To achieve an optimal antibiotic treatment, more appropriate doses, route of administration, and regimen should be employed to ensure tissue penetration. Adjustment of doses according to minimal inhibitory concentration, use of continuous infusion of beta-lactams, and use of inhaled antibiotics are issues that could impact on clinical results.
• Modification of empirical antimicrobial treatment (de-escalation, rescue therapy):
• The empiric antibiotic treatment must be reviewed once the culture results are available. De-escalation consists of a broad-spectrum initial antibiotic therapy, followed by a simplification of the regimen based on culture results and clinical evolution. Such strategy is associated with lower mortality. Rescue therapy is implemented when there is primary resistance on cultures or a poor clinical evolution.
• Evolution assessment:
• Clinical parameters such as fever and resolution of hypoxaemia (pO2/FiO2 ratio) are valuable markers of clinical resolution. Use of biomarkers such as CRP or procalcitonin are strategies to evaluate resolution and therapy duration. Optimal duration of therapy is unknown. A randomized trial concluded that outcomes are similar when treating patients for 8 or 15 days, but an individualized discontinuation of therapy based on clinical response may lead to even shorter courses of antibiotic treatment.
Pulmonary hypertension is said to occur when the mean pulmonary artery pressure exceeds 25 mmHg at rest or 30 mmHg with exercise. The term pulmonary arterial hypertension (PAH) denotes a series of apparently unrelated disorders that share the histopathological entity of plexogenic pulmonary arteriopathy (PPA). Examples include idiopathic PAH, familial PAH, and pulmonary hypertension associated with scleroderma, hepatic cirrhosis, HIV infection, and Eisenmenger’s syndrome. In addition, pulmonary hypertension can occur in association with cardiac diseases (left heart failure, mitral valve disease), respiratory disorders (emphysema, pulmonary fibrosis), pulmonary thromboembolic disease, and various miscellaneous conditions. Although these latter conditions are more common causes of pulmonary hypertension, the severity of pulmonary hypertension is usually less than seen in PAH and the histopathology is not PPA in nature.
Idiopathic PAH is typically described in young females, although with increasing awareness the condition is now being diagnosed in patients beyond the fourth and fifth decades of life. The incidence and prevalence of this condition is estimated to be 4 per million and 10 per million of the population, respectively. The prevalence of PAH is estimated to be in the region of 100 per million of the population. The incidence and prevalence of pulmonary hypertension in patients with cardiac and respiratory disorders are not precisely known, although they are believed to be considerably higher than for PAH.
Over the past 15 years, a number of efforts have been made to arrange conditions into groups according to common pathological and clinical features. Currently these conditions are classified into five groups, as outlined in Box 18.5.
Reprinted from Journal of the American College of Cardiology, 54, S1, Simonneau G, et al. Updated clinical classification of pulmonary hypertension, S43–54. Copyright (2009) with permission from Elsevier.
PPA occurs in a select group of disorders. The reason that this pathological entity occurs is not clear, although it is possible that the lung only has a finite number of responses to injury which feed into final common pathway mechanisms. This may explain why similarities occur in patients with conditions such as obliterative bronchiolitis following lung transplantation and those with obliterative bronchiolitis associated with rheumatoid disease or respiratory syncytial virus infection in childhood. Likewise, although many conditions have been implicated as causing ARDS, the pathology is similar regardless of aetiology. In PPA there is initial vasoconstriction and subsequent smooth muscle migration from the inner half of the media of muscular pulmonary arterioles into the lumen to become myofibroblasts capable of laying down either smooth muscle or fibrous tissue. The cells proliferate in a concentric fashion and ultimately obliterate the lumen. When sectioned, the vessels have the appearance of a cut onion, hence the term onion skin proliferation. As the radius becomes progressively compromised, the resistance to flow increases. At points of weakness in the vessel (proximally at branching areas) the vessel distends and ruptures. Haemorrhage occurs and primitive blood vessels grow into this area in a haphazard or plexiform arrangement. The combination of concentric laminar intimal (onion skin) proliferation and plexiform lesions is referred to as PPA. Some authors believe that plexiform lesions may represent a form of collateral circulation.
Why these particular changes occur in diseases with such diverse aetiology and clinical presentation is not understood. Immunoreactive cells in the lung for gastrin-releasing peptide and calcitonin may be important factors in smooth muscle migration. There is extensive ongoing research into endothelial dysfunction in patients with PAH.
PAH carries a poor prognosis, and for those patients with class IV New York Heart Association (NYHA) status, the 5-year actuarial survival is significantly lower than that for patients with lung, breast, prostate, colon, and gastric carcinoma. A median survival of 2.8 years has been reported for untreated patients in class III or IV NYHA. Survival and quality of life have improved for selected patients treated with agents such as endothelin receptor antagonists, prostacyclin analogues, and phosphodiesterase (PDE) inhibitors.
The following factors are useful in predicting mortality in PAH:
2. Functional capacity (NYHA or PAH class).
3. Exercise capacity (unencouraged 6-min walk test).
4. Haemodynamics (severity of right ventricular dysfunction).
5. Echo parameters (pericardial effusion carries worse prognosis).
Quality of life
Patients with PAH have similar quality-of-life scores when compared with those for patients with chronic obstructive lung disease and end-stage renal failure.
Early on, patients with pulmonary hypertension may be asymptomatic or exhibit dyspnoea with exertion. In the early stages of the disease, the non-specific nature of the symptoms may lead to either failure of diagnosis or incorrect diagnosis. Many patients have had their symptoms attributed to depression. As the condition progresses, the pulmonary vascular resistance rises and the cardiac output falls. At this stage, patients may change from having relatively few symptoms to experiencing dyspnoea, chest pain, palpitations pre syncope, or syncope with exertion and subsequently at rest. As the condition progresses further, right heart failure and death occur.
Median survival from diagnosis if NYHA functional class III or IV and untreated is 2.8 years.
Abnormalities in endothelial function with respect to vasoreactivity, intimal proliferation, and thrombus formation are believed to be important in the pathogenesis of this condition. Increasing attention has been given to endothelin 1 (which causes vasoconstriction and cellular proliferation), NO (which, via cGMP, promotes vasodilatation and is antiproliferative), and prostacyclin (which, acting via cAMP, also potentiates vasodilation and is antiproliferative). NO or prostacyclin analogues are important in managing patients with these conditions, as are endothelin receptor antagonists and PDE type 5 inhibitors. More recent research has focused on inflammatory mechanisms and anti-inflammatory agents.
Advanced pulmonary vasodilator therapy is usually prescribed for patients in groups 1 and 4 and for patients with PAH associated with renal failure. Current drugs available have improved quality of life and prolonged survival for some of these patients. Drug therapy can be given orally, e.g. sildenafil and tadalafil (PDE type 5 inhibitors), bosentan or macitentan (endothelin A and B receptor antagonists), or soluble guanylate cyclase stimulators (riociguat), by inhalation (epoprostenol), subcutaneously (prostacyclin analogues), and intravenously (epoprostenol). An oral synthetic analogue of prostaclycin is now available (treprostinil). Other treatment options include atrial septostomy and lung transplantation. A small number of patients (<10%) will respond to calcium channel blockers. These patients will have demonstrated a positive vascular reactivity test at cardiac catheterization, where the pulmonary artery pressure can be reduced to close to normal values following administration of agents such as NO with an increase in or unchanged cardiac output. Other therapeutic agents being considered include lipid-lowering drugs, anti-inflammatory agents, monoclonal antibodies, and antiplatelet agents. Further experience with these therapies is awaited.
Patients in NYHA functional class IV should be evaluated for bilateral lung transplantation. Some selected patients with chronic thromboembolic pulmonary hypertension may be candidates for pulmonary thromboendarterectomy. Arterial septostomy has been used to palliate patients with advanced PAH owing to its potential to decompress the failing right ventricle and improve cardiac index, but it is usually only used as a bridge to transplantation.
It is usual to commence patients on a PDE 5 inhibitor, and an endothelin receptor antagonist and other agents are subsequently added depending on clinical response. The precise indication for, and timing of, initiation of combination therapy is being defined.
Disease-causing mutations in bone morphogenetic protein receptor II (BMPR2) may underlie familial PAH. Mutations have been detected in 55% of families and show autosomal dominance with incomplete penetrance. Thus far, up to 26% of sporadic cases (idiopathic PAH) have BMPR2 mutations. BMPs are a family of secreted growth factors. BMPR2 regulates cell proliferation in response to ligand binding. Mutations lead to a loss of the inhibitory action of BMP on vascular smooth muscle cell growth. As a consequence, inappropriate cellular proliferation can occur.
Current theories on the pathophysiology of pulmonary hypertension
Patients may have a genetic predisposition (e.g. BMPR2 mutation) where there is a loss of the inhibitory regulatory effect of BMP on vascular smooth muscle. Should subsequent vascular injury occur as a consequence of drugs, toxins, autoimmune disease, or HIV infection, endothelial cell dysfunction can follow. This leads to inflammation and loss of local vasoreactivity, facilitating thrombus formation. Smooth muscle cell dysfunction can also occur independently. Disease progression and vascular remodelling ensue, PPA forms, and the pulmonary vascular resistance rises progressively.
PAH is a progressive and lethal disease whose initial symptoms can be non-specific. A comprehensive diagnostic approach is required to identify associated conditions and characterize haemodynamics and functional profiles. Although at present there is no cure for PAH, it is hoped that increasing awareness and understanding of disease mechanisms will facilitate the development of effective treatment modalities. Patients with PAH should be managed by specialist clinicians who are skilled in the diagnosis and management of the condition. Furthermore, advice from specialist centres should always be sought should patients become pregnant or require surgical intervention.
Multiple choice questions and further reading
Interactive multiple choice questions to test your knowledge on this chapter and additional further reading can be found in Appendix Chapter 18 Multiple choice questions and further reading