This chapter outlines the assessment of circulation in an injured patient including the pathophysiology, recognition and management of shock. When managing an injured patient it is vital to recognize the presence of shock early, and to rapidly identify and treat the cause. Following major trauma, by far the commonest cause of shock is hypovolaemia due to bleeding.
Other less common causes of shock include cardiogenic or neurogenic shock, and these must be anticipated during the initial assessment in cases where pre-morbid conditions or other features are suggestive.
The first management priority in any patient exhibiting signs of shock should be to ensure that the airway is secure and to administer oxygen to provide the highest FiO2 achievable (usually 85% by reservoir bag mask with a 12–15 L/min flow rate). The effort, rate and the effectiveness of breathing should also be assessed and any immediately life-threatening thoracic conditions managed as appropriate (e.g. decompression of a tension pneumothorax).
Assessment of circulation
Shock is a clinical diagnosis detected by the recognition of certain physical signs produced as a physiological response to poor tissue oxygen delivery. When assessing the injured patient, one of the primary concerns should be to ascertain an appropriate history, including the precise mechanism of injury so that attention can be focused on any specific areas of clinical concern. Enquiries should be made into any relevant past medical history, current regular medications, and drug allergies.
A ‘foot of the bed’ view should be taken initially and any obvious physical signs noted; for instance, the presence of pooled blood on the trolley or evidence of continued external haemorrhage. A co-ordinated trauma team approach should be followed and the patient exposed appropriately, maintaining dignity as much as possible.
Conscious level is a useful bedside marker of adequate cerebral perfusion and tissue oxygenation, and is often the first and most obvious thing apparent about a patient from the end of the bed. By definition, a fully alert and orientated patient must have a sufficient cardiac output to perfuse the cerebral cortex appropriately. In normal circumstances, cerebral autoregulation ensures a steady cerebral perfusion pressure with changes in blood pressure. However, this process will fail at extremes of range and is also affected by traumatic brain injury.
As cerebral hypoxia increases the level of consciousness will alter, beginning with anxiety, confusion, and agitation, and leading to aggression or combativeness and, if untreated, eventually to coma and death. Focal neurological changes, abnormal posturing, and signs of seizures may also occur.
The level of consciousness may also be affected in patients with a primary brain injury or by drugs (such as opiates or sedatives), thereby preventing further interpretation of the conscious level in relation to the presence, or absence, of shock.
The respiratory rate should be measured on arrival and at regular intervals during the initial assessment. This should be done by an observer counting the rate, as bedside physiological monitors that allow continuous respiratory rate measurement by way of transthoracic electrical impedance may give inaccurate results or fail to measure at all, especially where respiratory effort is poor or thoracic injury interferes.
The respiratory rate increases in response to reduced tissue oxygenation due to shock. In adults, a respiratory rate >20 breaths/min is considered abnormal. In children the normal range varies with age as shown in Table 7.1.
Table 7.1. Respiratory rate (RR) variation with age
The respiratory rate can also be affected by drugs or toxins, or by intrathoracic injury. Tachypnoea may result from pneumothorax or haemothorax, as well as anxiety and pain.
Skin colour and capillary refill
Patients with hypovolaemic shock typically exhibit pale, cool, and clammy skin due to peripheral vasoconstriction although skin may remain warm and vasodilated in sepsis.
Capillary refill time testing is a simple estimate of skin perfusion. This is performed by gentle compression of the skin for 5 s followed by measuring the time in seconds before normal colour returns once this pressure is released. Normal capillary refill time should be less than 2 s. The test is best performed in central areas of the body such as the sternum, in order to minimize the effects of cold on the peripheral circulation.
Heart rate and pulse volume
One of the earliest signs of shock is a relative tachycardia. A heart rate above 90–100/min in an adult may represent shock. Hypovolaemic shock usually presents with a weaker, thready pulse felt as peripheral perfusion diminishes. Septic shock may present with a bounding pulse.
In children, the upper limit of normal heart rate differs with age as shown in Table 7.2.
Table 7.2. Heart rate (HR) variation with age
However, an increased heart rate is an unreliable measure of shock. Tachycardia may have several other causes, including pain and anxiety, and is not always present in significant shock, for example, in young fit patients, those on drugs such as ß–blockers or the elderly.
The traditional view that various pulse points equate to certain systolic blood pressure values has a poor evidence base. However, the presence of a radial pulse does suggest that perfusion is at least sufficient to reach the peripheral circulation and, by implication, organs such as the brain, heart, and kidneys. Vascular injury, such as traumatic arterial transection may affect distal pulses and will therefore prevent any useful estimation of blood pressure in this way.
Non-invasive blood pressure (NIBP) monitoring should be carried out with appropriate measurement intervals depending upon the clinical situation. An automated oscillometric system produces numerical values for the systolic, diastolic and mean arterial pressures during a microprocessor controlled sequence of inflation and deflation of the pressure cuff. Failure to measure or false readings can be caused by an incorrectly-sized cuff or by the presence of irregular cardiac rhythms, such as atrial fibrillation.
Normal blood pressure varies with age, gender, and clinical reasons such as cardiovascular drug therapy and medical conditions including hypertension. Normal systolic blood pressure in children (mmHg) can be estimated by the formula 80 + (age in years × 2).
The pulse pressure narrows in the early, compensated stages of hypovolaemic shock, and in cardiogenic shock, due to raised systemic vascular resistance from vasoconstriction. Pulse pressure generally widens in septic, anaphylactic and neurogenic shock, due to reduced peripheral vascular resistance. Postural hypotension may support the diagnosis of shock, especially due to hypovolaemia.
Non-invasive cardiac output estimation
Several non-invasive devices are available that estimate cardiac output at the bedside and may be used to help detect signs of shock. Transcutaneous Doppler, impedance cardiography and aortovelography methods used in such systems should only be relied upon to record changes in cardiac output, rather than providing reliable absolute measurements.
Technically non-invasive (although requiring sedation or anaesthesia to insert the probe), transoesophageal echocardiography (TOE) may also be utilized as a method to estimate cardiac output and demonstrate signs of shock.
Urine output may be considered a non-invasive measure of shock in the non-catheterized patient. Failure to produce an adequate urine output may be a delayed sign of shock, although it may also be due to trauma to the urological tract, acute urinary retention due to neurological injury or from other causes of renal failure. A urine output of at least 0.5 mL/kg/h in adults, and at least 1–2 mL/kg/h in children, signifies that there is adequate renal perfusion.
Response to intravenous fluid boluses
Indirect measurement of the presence and extent of shock can be carried out by assessing the physiological response to intravenous fluid boluses. Improvement following fluid administration may support the diagnosis of hypovolaemic, neurogenic, septic, or anaphylactic shock. Deterioration following intravenous fluid therapy may be noted with cardiogenic shock.
A transient response to intravenous fluid therapy may suggest a more severe degree of shock or ongoing haemorrhage.
Causative volume loss estimates
Loss of circulating blood volume may be predictable from the apparent injuries. In addition to external haemorrhage or large open wounds, the two most important examples of apparent fluid losses are due to thermal burns and fractures. Fluid deficit from burn injury can be calcu-lated according to the body surface area affected, and fractures also have predictable blood volume losses. For example, closed femoral fractures may lose up to 1500 mL blood and closed tibial fractures up to 500 mL in adults.
Invasive monitoring for shock
In general, invasive monitoring is required for groups of patients needing a higher level of care such as coronary, high-dependency or intensive care patients. The principle behind invasive monitoring is to enable the haemodynamic status to be more closely monitored than is possible by non-invasive techniques. Invasive monitoring involves risk that must be balanced against the benefit gained on an individual patient basis.
A variety of invasive lines are used in clinical practice including dialysis lines, Hickman lines and peripherally inserted central catheter (PICC) lines. The emphasis of this section is placed on the use of central lines and arterial lines for monitoring of the shocked trauma patient.
Bladder catheterization is not technically an invasive form of direct haemodynamic monitoring for shock; it is nonetheless ‘invasive’ from a procedural point-of-view. Catheterization enables close monitoring of urine output although with the associated risk of introducing infection.
Electromechanical devices: the basics
Before considering the relevant techniques and theory for invasive monitoring, it is worth summarizing how the relevant devices work and outline some of the main errors than can occur with measurements.
The term manometer usually refers to a type of liquid column pressure measuring instrument enabling bedside pressure monitoring without the need for electronic devices. A column of fluid in direct continuation with the required line is measured in height against a scale (usually in cm of water). This technique is appropriate for central venous pressure (CVP) monitoring, but not for arterial pressure, which is usually too high to measure in this manner.
A transducer is a device that converts energy from one form to another. Pressure transducers used for monitoring through central and arterial lines measure electromotive forces via a strain gauge variable transducer. Most pressure transducers contain four strain gauges, which form the four resistances in a Wheatstone bridge on a tiny printed circuit board and diaphragm.
Pressure transducers are connected via a column of fluid (usually sodium chloride 0.9%) at a pressure of 300 mmHg. This column of fluid moves back and forth with each pulsation causing the transducer diaphragm to move. This movement results in a change in resistance and current flow, which is measured and electronically converted in order to display pressure readings.
Common sources of error Confounding errors in measurements can arise from:
• The system not being calibrated and zeroed.
• Inappropriate damping of the system.
• The transducer not being at the level of the heart.
• The system not being pressurized to 300 mmHg.
The CVP is the pressure found within the right atrium and great veins of thorax. Normal pressure should be 0-8 cm H2O. Hypovolaemia and vasodilatation will result in a fall in CVP due to reduced venous return. CVP can also be used to assess the efficacy of fluid resuscitation, suggested to be adequate if a sustained rise in CVP is demonstrated following an appropriate fluid challenge.
Indications For continuous monitoring of haemodynami-cally compromised patients and to enable responsive replacement of circulating volume in accordance with CVP. Central venous access may also be required for inotrope and vasopressor infusions or for other drugs for which peripheral administration is not recommended.
Other indications include:
• Facilitating the insertion of pacing lines.
• Regular blood sampling, including mixed venous gases.
• Provision of renal dialysis.
• Administration of parenteral nutritional support.
Contraindications Contraindications to the insertion of central venous catheters are generally relative and related to the site of insertion and mechanism of injury. Injury to the upper thorax or neck may prevent use of the internal jugular or subclavian veins, leaving the femoral vein as the most viable option. Maintaining appropriate sterility of the femoral region is difficult, although any risk of infection must be balanced against the urgency of achieving appropriate access. Femoral lines may not truly represent right atrial pressure and must be interpreted with caution.
There is an increased risk of bleeding from the insertion site in patients with coagulopathies, or who are known to be on anticoagulation therapy. Obesity or anatomical abnormalities can make insertion of lines more problematic, and may be more risky in agitated or confused patients without the use of sedation.
Central line insertion may also be difficult in patients whose respiratory function is compromised and who cannot be laid flat. Very rapid respiratory rates may also increase the risk of air embolus from jugular or subclavian line insertion due to lower intrathoracic pressures.
Complications and limitations Central line insertion is associated with a number of potential complications, some of which are potentially life-threatening:
• Pneumothorax (pleural puncture).
• Arterial puncture or nerve damage.
• Cardiac arrhythmias (direct intravascular stimulation).
• Air embolism.
• Infection by skin commensals.
• Occlusion and thrombosis.
Normal central venous lines (triple or quad lumen) are not always the best form of access for rapid fluid administration in emergency situations as their relatively narrow gauge and longer length may restrict maximum flow rates compared with larger peripheral lines. However, insertion of larger lumen lines, such as vascular catheters (normally used for emergency dialysis) or Swan–Ganz catheter introducer sheaths can permit very rapid central infusions.
Technique of insertion The identification and cannulation of central veins may be difficult in hypovolaemic patients. The 2002 NICE guidelines recommend the use of ultrasound guidance where available to facilitate safer insertion. A standard landmark technique may still be appropriate in the emergency situation. ECG monitoring is required in case of arrhythmias.
Once the vein is located, a percutaneous Seldinger technique is used to insert the catheter. The Seldinger technique comprises the following general steps:
• A ‘seeker’ needle is passed into the vessel.
• A guide wire is passed through needle into vessel.
• The needle is removed leaving the guide wire in place.
• A dilator passed over the guide wire to widen skin the incision.
• The cannula is introduced into the vessel over the guide wire.
• The guide wire is removed and the catheter secured.
In case of inadvertent arterial puncture, firm pressure should be applied to the site for 5–10 min or until the site has stopped bleeding completely. The catheter position must be checked by x-ray (i.e. chest x-ray for jugular or subclavian lines, or pelvis x-ray for femoral lines), as well as to exclude a pneumothorax.
Pulmonary artery catheterization Central line access is required in order to introduce this type of catheter. A flow-directed balloon-tipped pulmonary artery catheter is floated into the pulmonary artery via the right atrium and ventricle, usually from a right internal jugular site. Pulmonary capillary wedge pressure (PCWP) is the pressure measurement at the tip of the catheter with the balloon inflated and, in most patients, represents left atrial filling pressure and, therefore, left ventricular end-diastolic pressure.
As with CVP measurements, interpretation of PCWP measurements is more useful when monitoring trends rather than single readings. The response of PCWP to fluid resuscitation may be used to indicate intravascular volume status. The use of pulmonary artery catheters is controversial in critical care, with no clear evidence of any benefit to overall morbidity or mortality.
Arterial lines provide both measurements of blood pressure and a waveform, the shape of which can also provide useful information regarding the haemodynamic status of the patient. Stroke volume and cardiac output can be derived from the area under the systolic part of the curve. Myocardial contractility may be indicated by rate of pressure change over time. Hypovolaemia is suggested by a low dicrotic notch, narrow waveform, and swinging peak pressures with the respiratory cycle.
Indications The main indication for insertion of an arterial line in trauma patients is to allow continuous direct arterial blood pressure monitoring. Arterial line measurement provides a continuous reading and is more accurate than non-invasive methods. It will also enable regular arterial blood gas sampling and measurements. Arterial BP trend is often more important than single readings. Several variables can affect blood pressure readings including age and the existence of pre-morbid medical conditions. Decreased aortic compliance in the elderly may result in higher peak pressures.
Contraindications As with central lines, there may be an increased risk of bleeding from the insertion site or haematoma formation in patients with coagulopathies. Infection may also occur after insertion, with risk increasing the longer the line remains in situ.
Complications and limitations The potential complica-tions of arterial line insertion are similar to those associated with central lines as listed. User error may minimize the benefit of arterial pressure measurement. Air bubbles, blood clots, a soft diaphragm, or soft tubing may cause damping of the arterial waveform signal, preventing accurate interpretation. Damping is caused by dissipation of stored energy resulting in a progressive diminution of amplitude of oscillations. Increased damping lowers the systolic pressure and elevates the diastolic pressure, although mean arterial pressure is unaltered. The transducer should be at the level of the right atrium; raising or lowering the transducer will result in errors.
Technique of insertion The common sites of insertion of arterial lines are the radial and brachial arteries. Femoral or dorsalis pedis arteries may also be used. Catheters are inserted either using a catheter over needle technique similar to peripheral venous cannula insertion [e.g. Floswitch™ (BD)], or by a Seldinger wire guided insertion technique similar to that used for inserting central lines [e.g. Leadercath (Vygon)]. Normal catheter sizes are 18–22G. Similar to central lines, the arterial line system consists of the cannula, connecting catheter, transducer and electrical monitor with appropriate connections.
In layman’s terms, the word shock is commonly used in the context of a sudden surprising event or experience. From a medical point of view the term shock is used to describe a specific physiological syndrome, which can occur due to several different causes and pathological processes, although will present with similar clinical features.
The Online Medical Dictionary defines shock as:
… A condition of profound haemodynamic and metabolic disturbance characterized by failure of the circulatory system to maintain adequate perfusion of vital organs; it may result from inadequate blood volume (hypovolaemic shock), inadequate cardiac function (cardiogenic shock) or inadequate vasomotor tone (neurogenic shock, septic shock) …
Following trauma shock can occur as a result of several mechanisms, the most common of which is hypovolaemia secondary to bleeding. Hypovolaemic shock is associated with considerable mortality. In shock from other causes, such as cardiogenic or septic shock, the mortality exceeds 50%. It is, therefore, vital to recognize and appropriately manage signs of shock rapidly in trauma patients. The various consequences of shock are outlined below.
The causes of shock can be divided as follows:
• Cardiogenic shock:
• Distributive shock
The pathophysiology of shock
Shock is a systemic clinical syndrome that can be said to exist when perfusion is insufficient to meet the metabolic demands of body tissues. In severe shock this will manifest at both a cellular and organic level due to hypoxia, failure of normal cellular metabolism, and subsequent acidosis. This failure tends to represent a vicious spiral where deteriorating perfusion, metabolism, and acidosis produce further cellular and organ dysfunction, thus worsening the situation.
In order to understand the pathophysiological consequences of shock, it is important to review a number of relevant basic physiological functions and processes.
Aerobic respiration is the normal process by which cells generate much of their energy (mainly stored in the form of adenosine triphosphate—ATP) and is dependent on oxygen. Much of this process takes place in mitochondria.
ATP, and other stored energy compounds such as phosphorylcreatine (found in muscle), are required for normal cellular functioning. Without ATP, cells will be unable to utilize available energy sources efficiently, will fatigue rapidly and may eventually die. Mitochondria are also responsible for many other cellular mechanisms, which will also fail in anaerobic conditions.
• Glycolysis (anaerobic step): glycolysis involves the creation of two pyruvate molecules from one glucose molecule producing a net gain of two molecules of ATP in the process.
• Pyruvate decarboxylation: each pyruvate molecule is oxidized to acetyl-CoA and carbon dioxide in the mitochondria producing three ATP per pyruvate molecule. The process is also known as the transition or link reaction, by linking glycolysis to the Krebs cycle.
• Tricarboxylic acid cycle: the tricarboxylic acid cycle (or Krebs cycle) takes place within the mitochondrial matrix in aerobic conditions. The cycle is an 8-step sequence of reactions producing ATP molecules via the oxidative phosphorylation of associated co-enzymes in conjunction with the electron transport chain. Carbon dioxide is also created during this cycle.
• Oxidative phosphorylation (electron transport chain): This occurs in the mitochondrial cristae where ATP is synthesized by the ATP synthase enzyme by the phosphorylation of ADP. This process is powered by a chemiosmotic gradient (proton gradient) across the inner mitochondrial membrane from oxidation of the co-enzymes produced from the Krebs cycle.
Overall, the theoretical total yield of aerobic respiration from one glucose molecule is 36–38 ATP, assuming all reduced coenzymes are used for oxidative phosphorylation. In reality, the likely maximum is around 30 ATP per glucose molecule due to losses and some energy use throughout the various pathways.
When oxygen delivery is limited, such as in the case of shock, pyruvate is metabolized by anaerobic respiration. Anaerobic respiration is far less efficient at using the energy from glucose and will produce lactic acid as a waste product. This can occur in skeletal muscle and red blood cells.
As stated above, aerobic metabolism can generate a maximum yield of 36–38 ATP molecules per glucose molecule. If perfusion and oxygen delivery are sufficiently impaired by shock that cells have to rely upon the anaerobic metabolic pathway, only two ATP molecules are generated per molecule of glucose.
Oxygen delivery and consumption
The theoretical maximum carrying capacity of oxygen is 1.39 mL O2 per g Hb, but in vivo measurement gives a maximum capacity of 1.34 mL O2 per g Hb. This number is known as Hüfner’s constant.
Blood oxygen content
Blood oxygen content mainly relies upon the oxygen carrying capacity of haemoglobin and its oxygen saturation level. A small amount of oxygen is also carried dissolved in plasma (unbound to Hb), which is dependent on the partial pressure of oxygen in solution. This is taken into account in the following equation to calculate the arterial oxygen content (CaO2):
CaO2 = O2 bound to Hb + O2 dissolved in plasma
CaO2 = (Hb × SaO2% × 0.01 × 1.34) + (0.0225 × PaO2)
Similarly, in order to calculate venous oxygen content, the values of mixed venous oxygen saturation (SvO2) and venous partial pressure of oxygen (PvO2) are substituted.
In shock, hypoxia or loss of haemoglobin will result in impairment of CaO2. Total oxygen carrying capacity is diminished, thus affecting oxygen delivery.
Oxygen delivery (DO2) represents the amount of oxygen being delivered to the peripheral tissues per unit time. It is calculated by the product of the cardiac output (Q) and the arterial oxygen content (CaO2). As the oxygen content of blood is calculated per 100 mL blood, the CaO2 is multiplied by 10 in the equation, as follows:
DO2 = Q × CaO2 (mL/L) × 10 = 850–1200 mL/min
Oxygen consumption (VO2) represents the amount of oxygen utilized by body tissues per unit time. It is calculated by the product of the CaO and the difference between arterial and mixed venous oxygen content.
VO2 = Q × (CaO2 – CvO2) = 240–270 mL/min
The primary management goal in shock is to ensure adequate oxygen delivery to enable tissues to meet their metabolic demands, in turn represented by a balance between VO2 and DO2. The extraction ratio is the ratio of VO2 to DO2 and is expressed as a percentage. The normal extraction ratio is around 25%, but can double to 50% if tissue oxygen demand increases. The key to managing traumatic shock in practical terms therefore involves returning the cardiac output, oxygen saturations and haemoglobin as near to normal values as possible to maximize DO2. This will include appropriate oxygen supplementation, fluid resuscitation and blood transfusion as required.
Metabolic (cellular) consequences of shock
Hypoperfusion and subsequent inadequate delivery of substrates and oxygen fails to meet the metabolic requirements of the tissues. Cells are not able to sustain efficient energy production via the aerobic method and respiration will occur anaerobically. This metabolic dysfunction results in production of lactic acid from anaerobic respiration resulting in systemic acidosis. In addition to acidosis, cellular metabolism will no longer be able to generate enough energy to power the vital components of normal cellular homeostasis. The cellular consequences of this include disruption of cell membrane ionic pumps with accumulation of intracellular sodium and cytosolic calcium. Hyperkalaemia occurs due to the subsequent release of intracellular constituents.
An initial rightward shift of the oxyhaemoglobin dissociation curve (ODC) will occur although sustained acidosis will eventually cause the red cell 2,3-DPG to decline and shift the ODC back towards normal. Metabolic acidosis also has negative effects on numerous protein and enzyme functions, such as the coagulation cascade. Cellular gene expression is affected causing deterioration in cell function and signalling.
Tissue injury due to trauma itself causes release of inflammatory mediators resulting in vasodilation, microvascular permeability, and increased metabolic compromise.
If anaerobic conditions continue unchecked, cells swell as water follows the rise in intracellular sodium, cell membranes break down eventually leading to cell death and subsequent organ dysfunction (see below).
Organic (macroscopic) consequences of shock
Metabolic acidosis can cause significant physiological effects, particularly affecting the respiratory and cardiovascular systems. If cellular death is widespread this can result in multiple organ dysfunction and eventual failure.
Hyperventilation (Kussmaul respiration) is the compensatory response to metabolic acidosis. Hyperventilation in the trauma patient may therefore represent severe metabolic acidosis due to shock, or a primary respiratory cause such as pneumothorax or haemothorax.
Acidosis will depress myocardial contractility and result in sympathetic over-stimulation, leading to tachycardia, vasoconstriction, and a decreased arrhythmia threshold. Indirect effects may result from hyperkalaemia. Other effects that may be noted include:
• Resistance to the effects of catecholamines.
• Peripheral vasoconstriction.
• Pulmonary vasoconstriction.
Sympathetic stimulatory effects and the release of catecholamines usually counteract direct myocardial depression, while plasma pH remains above 7.2. At systemic pH values less than this, direct depression of myocardial contractility usually predominates.
Physiological consequences of shock
The main physiological consequences of shock are listed below, generally in the sequence given below:
• Metabolic acidosis.
• Oliguria leading to acute renal failure.
• Hepatic, gastrointestinal and pancreatic impairment.
• Acute respiratory distress syndrome (ARDS).
• Disseminated intravascular coagulation (DIC).
For the purposes of discussion, shock may be divided into three phases. There is no abrupt transition between them and clinical progression through these stages is variable, being dependent upon the cause, as well as individual patient factors, such as age and associated co-morbidities.
In the initial stages of shock the metabolic effects are just starting to become apparent. Following the onset of shock, several physiological mechanisms are employed in an attempt to reverse these metabolic effects.
As the signs of shock become more apparent various homeostatic mechanisms attempt to improve tissue perfusion and oxygen delivery. These consist of various neuroendocrine reflexes involving sympathetic activation and renal conservation of salt and water. Increased cardiac output is brought about primarily by vasoconstriction, tachycardia, and reduced renal fluid losses.
As blood pressure falls, arterial baroreceptors detect hypotension and trigger activation of sympathetic chain of the autonomic nervous system. The resulting catecholamine release causes tachycardia and vasoconstriction (skin, viscera, and kidneys), thus improving stroke volume and cardiac output. As a result of the underlying metabolic acidosis, hyperventilation attempts to reduce CO2 levels and thereby raise the blood pH nearer to normal.
The renin-angiotensin axis is also activated and antidiuretic hormone (ADH) is released in order to conserve intravascular fluid. This causes vasoconstriction of the renal and gastrointestinal systems in order to redistribute blood volume to the heart, lungs and brain. Diminished renal blood flow causes the characteristic oliguria. Corticosteroid secretion also increases as part of the stress response.
If left untreated, normal compensatory mechanisms will eventually fail, resulting in worsening perfusion, acidosis, and cellular dysfunction. Inflammatory mediators are released and further depress the cardiovascular system, particularly causing myocardial depression and inducing fluid loss from the intravascular compartment.
Hydrostatic pressure increases along with inflammatory mediator release lead to leakage of fluid and protein into the extravascular space. Arteriolar smooth muscle and precapillary sphincters relax such that blood pools in the capillaries and, as fluid is lost, blood concentration and viscosity increases, causing sludging of the micro-circulation and microvascular thrombosis.
As the gastrointestinal tract becomes ischaemic, bacteria and endotoxins (typically lipopolysaccharides, LPS) may enter the blood stream via the portal circulation, which causes further promotion of the systemic inflammatory response. Hypoperfusion-reperfusion injury may represent a second hit as the cardiovascular consequences of shock progress.
This is also referred to as irreversible shock. As cardiovascular and metabolic function deteriorates further, the resulting organ damage is too severe for recovery to take place, even if appropriate resuscitation is commenced. Signs of multiple organ failure will appear and the later complications of shock may become apparent such as renal failure, ARDS or DIC.
Classes of shock
Haemorrhagic shock has traditionally been classified by the volume of blood loss and the resultant physiological signs and symptoms. However, this classification system does not take into account the multifactorial nature of shock or individual patient factors that may produce variance from these.
Despite its limitation, this classification may be useful when considering the effect of increasing volumes of blood loss on a normal, healthy adult:
• Even a rapid blood loss of up to 500 mL is likely to be well tolerated and compensated.
• By 1000 mL the initial signs of tachycardia and postural hypotension are likely to appear.
• Above 1500–2000 mL shock will definitely be apparent with signs of hypoperfusion and metabolic acidosis.
Later consequences of shock
Multiple organ dysfunction syndrome
Defined as a syndrome of organ dysfunction affecting two or more organs, this involves a severe inflammatory response and tissue injury associated with hypoperfusion. Multiple organ dysfunction syndrome (MODS) usually occurs days after sepsis or SIRS, and can also follow severe trauma, especially following massive haemorrhage and blood transfusion.
Acute lung injury and ARDS
Acute lung injury (ALI) is a syndrome of inflammation and increased permeability of lung tissue associated following severe trauma and massive blood transfusion, amongst others. It usually occurs within 2–3 days of the injury or insult. ARDS is the most severe form of ALI and distinct from this purely on the basis of the PaO2/FiO2 ratio.
Continuous haemodynamic monitoring will be required for all trauma patients exhibiting signs of shock. In the initial stages, basic physiological parameters are likely to be sufficient in order to guide management and clinical decision making.
More accurate beat-to-beat physiological monitoring will be required in more complex or severe cases and where critical care interventions are required, such as endotracheal intubation and ventilation.
Minimum monitoring standards
Continuous pulse rate (ECG rhythm), pulse oximetry, and non-invasive blood pressure are convenient and safe to monitor and constitute the minimum monitoring standards required when dealing with a trauma patient. Signs of shock may be indicated by a rise in heart rate or fall in blood pressure without an apparent alternative cause (e.g. pain causing tachycardia). Oxygen saturation may also fall, or the signal trace may fail to pick-up properly, due to poor peripheral perfusion.
Regular measurement of urine output, facilitated by urinary catheterization and the use of an hourly urine collector bag, can be useful as a measure of the response to fluid resuscitation in shocked patients. Maintenance of a urine output greater than 0.5 mL/kg/h would suggest adequate renal perfusion and intravascular volume.
Quantitative measures of shock
By defining shock as a syndrome of insufficient tissue perfusion to maintain adequate metabolic demands a quantitative measure of shock could be said to be that which can provide a measurement of perfusion. Changes in cardiac output or in the extraction ratio of DO2 to VO2 may be useful to measure shock and the response to resuscitation. Most of these are invasive techniques requiring central venous or arterial line insertion. More recently, various bedside monitoring devices have become available that may be useful in shock due to trauma.
Cardiac output measurement
A variety of techniques may be employed to measure cardiac output incorporating the Fick principle (e.g. NICO®), dilution by thermal, dye or lithium methods, Doppler, echocardiographic or impedance plethysmography. As discussed previously, accurate measurements of cardiac output are possible using pulmonary artery catheters, although this is associated with considerable risk.
Combined dilution and arterial waveform analysis systems may enable bedside monitoring (e.g. PiCCO™ or LiDCO™). Systems such as these could be used to identify trends in shock and guide ongoing fluid resuscitation of severe or complex trauma patients in emergency settings, although their use is limited by a regular need for recalibration and the risks associated with attendant lines.
Surrogate markers of shock
Lactate is produced by skeletal muscle, brain, gut, and erythrocytes, and is metabolized mainly by the liver and kidneys. Raised plasma lactate levels can indicate the severity of hypoperfusion and hypoxaemia due shock. For a significant increase in blood lactate to occur, lactate must be released into the systemic circulation, and the rate of production must exceed uptake and metabolism.
Normal plasma lactate levels are 0.6–1.8 mmol/L. A rise in the level above 2.0 mmol/L may therefore indicate hypoperfusion. Lactic acidosis is characterized by persistently increased blood lactate levels (usually >5 mmol/L) in association with metabolic acidosis. Rate of change, rather than individual levels, may be more useful as a marker of shock and the response to clinical interventions and resuscitation.
Mixed venous oxygen saturation
Mixed venous blood must be obtained from the right atrium or pulmonary artery and therefore requires a central venous line. Mixed venous oxygen saturation can be used along with arterial oxygen content to estimate oxygen consumption and as an indicator of haemodynamic failure. Delivery of oxygen can be said to be at a critical level at SvO2 of <50% (normal is 75%). Continuous monitoring may also be possible via pulmonary arterial catheters.
The indirect measurement of gastric intramucosal pH by a balloon tonometer placed in the stomach can be used as an indicator of gastric mucosal oxygen delivery and consumption. Acidosis may indicate impaired gastrointestinal oxygen delivery or utilization, and has been proposed as a surrogate indicator of splanchnic hypoperfusion. This may prove useful as a guide to fluid resuscitation and onward critical care management in trauma, although the technique has not been accepted widely due to its cost, technical difficulty, and poor specificity.
Hypovolaemia due to haemorrhage is the most common cause of shock in trauma patients, and should be anticipated and excluded before considering other potential, although less frequent, causes such as neurogenic or cardiogenic shock.
The injury mechanisms responsible for haemorrhage following trauma may be divided into four main groups:
• Capillary bleeding (generally oozing in nature).
• Arterial or venous bleeding due to vessel damage.
• Bleeding from organs due to laceration or rupture.
• Bleeding from bone marrow due to fractures.
Each of these may be subdivided into external or internal haemorrhage, depending upon the presence or absence of local open wounds. External haemorrhage is more likely in the context of penetrating injury or blunt injury causing lacerations or open fractures. Internal haemorrhage is often well concealed until the signs of shock become apparent. Pain and agitation may be the only initial features.
Significant burn injuries may also reduce circulating blood volume due to loss of plasma (although they will not reduce the haemoglobin concentration as red cells are not lost). This is unlikely to cause shock during the initial phase of assessment and management.
Haemorrhage can be classified according to the actual amount of blood lost or as a percentage of the circulating blood volume. Classification systems that rely upon physiological parameters are limited by individual patient factors and co-morbidities.
Basic physiological principles
The average fluid proportion of total body weight in lean adults is between 55 and 60%, which can be divided roughly into 2/3 intracellular fluid (ICF) and 1/3 extra-cellular fluid (ECF), of which 80% is interstitial fluid and 20% plasma.
Circulating blood volume comprises around 7% of the total body weight (70–80 mL/kg), therefore, a 70-kg person will have a total blood volume, also referred to as mean normal blood volume (MNBV), of around 5000 mL.
Cardiac output (CaO) is the volume of blood pumped per minute and is the product of the stroke volume and heart rate. The normal CaO for a fit 70-kg person is around 5000 mL/min, which therefore represents the total blood volume circulating around the body every minute. The potential for rapid exsanguination due to major blood vessel injury is therefore high.
Normal cardiac output is distributed approximately in the following proportions:
• Liver 25%
• Kidneys 22%
• Muscle 20%
• Brain 14%
• Heart 5%
• Other 14%
As can be seen, injury to the liver can be associated with considerable haemorrhage—theoretically the full blood volume in only a few minutes.
Haemostasis involves a series of rapid and complex processes both at a local and systemic level. Smooth muscle constricts and endothelium becomes procoagulant at the site of vessel injury. Platelets are activated and begin to aggregate at the site, establishing a temporary plug. Following this, fibrin binds with the platelet plug to form a definitive clot. The coagulation pathway is a cascade mechanism involving many circulating factors. At the same time, various inhibitory mechanisms ensure coagulation is confined to the site of the injury.
Acquired coagulopathy may develop in severe haemorrhage due to consumption of clotting factors or dilution due to the administration of fluids or blood products. In response to blood loss, the body also tries to conserve circulating volume by shifting fluid from the extra-vascular compartment to the intravascular compartment. This may exacerbate the haemodilutional effect.
Normal haematological values
Normal values (for a 70-kg patient) are:
• Circulating volume 5000 mL
• Cardiac output 5000 mL/min
• Red blood cells 4–6.5 ×1012/L*
• Haemoglobin 11.5–18 g/dL*
• Haematocrit 0.37–0.54*
• Platelets 150–400 × 109/L
• Prothrombin time (PrT) 12–15 s
• APTT 23–42 s
*Values are generally lower in women than in men
The six compartments
The concept of compartments is useful when considering the potential sources of life-threatening haemorrhage secondary to trauma. Each compartment can be defined as a potential space into which haemorrhage may occur. This can facilitate a systematic review of the trauma patient with signs of haemorrhagic shock where the site of bleeding is not immediately apparent.
The six compartments are listed below:
External haemorrhage is usually obvious but can be concealed. Occasionally the cause of haemodynamic instability is only established once the resuscitation trolley is moved, whereby a large pool of blood is apparent on the floor. A thorough physical examination is vital to discover any external sites of bleeding.
The quantity of blood loss externally is extremely difficult to judge by observation alone. A cupful of blood goes a long way on a white floor.
Scalp wounds deserve a particular mention. They can continue to bleed profusely, despite being covered with a dressing, so early attention should be paid to closing the wounds with large sutures (which may be a temporary measure) and achieving haemostasis.
Bleeding into the chest can occur as a result of lung parenchymal injury, as well as injury to the blood vessels in the chest and the intercostal vessels.
Clinical examination may reveal bruising, pain, reduced expansion, dullness to percussion, and reduced breath sounds. Blood in the chest can be confirmed by a chest X-ray as part of the primary survey. Most thoracic bleeding can be managed with tube thoracostomy.
Bleeding into the abdomen is common, but not always obvious. Clinical clues may be present such as bruising to the abdominal wall, abnormal movement, involuntary muscle guarding, or tenderness to palpation, and absence of bowel sounds. However, in the majority of cases clinical examination needs to be supplemented by further investigation, commonly by ultrasound (FAST), to detect free fluid, and CT if the patient is stable enough.
Concealed intra-abdominal haemorrhage should be assumed if the patient is haemodynamically unstable without any other obvious cause following blunt trauma. Any intra-abdominal bleeding is referred to as non-compressible haemorrhage and is likely to be controlled only by surgery.
Injury to the pelvis should be assumed and excluded on X-ray during the primary survey. In the pre-hospital environment (or emergency department if not already done), when the mechanism of injury suggests a possible pelvic injury, a pelvic splint should be applied and left in place until significant injury is excluded.
Significant bleeding can occur from extremity fractures, particularly if they are open or multiple. Long bone fractures should be splinted and, in the case of femoral fractures, traction splints applied to reduce bleeding. Clinical examination and X-ray confirmation give the diagnosis.
The retroperitoneal space contains the abdominal aorta, inferior vena cava, part of the duodenum, pancreas, kidneys, and ureters, and part of the colon. The lower part of the retroperitoneal space lies within the pelvic cavity.
The retroperitoneum is hidden from view in the resuscitation room. It can only be visualized on CT, where occult haemorrhage into the retroperitoneum is sometimes found.
Uncontrolled haemorrhage accounts for around 40% of mortality in major trauma and the survival rate for trauma patients requiring massive transfusion is around 50%.
Early detection and control of haemorrhagic shock is therefore of paramount importance. The primary aim is always to restore adequate oxygen carrying capacity to meet the physiological needs of the patient, taking into account any pre-existing medical conditions.
The main objectives can be summarized as follows:
• Achieving rapid haemostasis.
• Restoring and maintaining tissue oxygen delivery.
• Restoring and maintaining adequate tissue perfusion.
• Restoring and maintaining normal clotting function.
In all cases of haemorrhagic shock, the priority is to control the source of bleeding.
The <C>ABCDE paradigm
Experience of trauma in the military setting, especially from blast and ballistic mechanisms, has resulted in changes to the way in which military personnel assess and treat patients. This new paradigm is now increasingly accepted in civilian care. The emergency treatment algorithm ABC has now been replaced by <C>ABC, where the first <C> stands for catastrophic haemorrhage.
External haemorrhage control
New methods of external haemorrhage control have been developed as a result of military medical trauma experience and include new kinds of compressive elastic dressings, the early use of tourniquets for limb trauma and topical haemostatic agents (THA).
A step-wise approach may follow:
Dressing → Pressure & Elevation → THA → Tourniquet
Direct pressure and limb elevation
Direct pressure and elevation are the first priorities for all compressible external haemorrhage. This approach is most effective for limb and extremity injuries.
Topical haemostatic agents
Increasing military experience of these agents has led to their routine, protocol-led use in situations where external haemorrhage is either non-compressible or other measures have failed to control exsanguination.
QuikClot® is a granular zeolite powder derived from volcanic rock, which creates a matrix within the wound allowing the formation of clot around the damaged blood vessel. It was introduced into UK Defence Medical Services (DMS) practice in April 2004. When the material comes into contact with blood it takes up water molecules, concentrating local platelets and clotting factors, and thereby promoting natural clotting mechanisms at the bleeding point. Animal studies have demonstrated improved survival and reduced blood loss in vascular and soft tissue injury, and severe liver injury. Contraindications to its use include open head injuries, open thoracic wounds, and abdominal injury with exposed viscera.
QuikClot® is chemically inert although it will generate an exothermic reaction in the presence of water. As a result, a dry wound and surrounding skin is required to prevent thermal damage to local tissue. A sealed, porous teabag form has also been developed in order to avoid known problems associated with administering the granular form.
HemCon® (HemCon Medical Technologies, Inc.)
HemCon consists of a pliable dressing impregnated with chitosan acetate (derived from the exoskeleton of crustaceans including shrimp and crabs). The amino group in chitosan is positively charged and soluble in acidic to neutral solutions making it bio-adhesive. It readily binds to negatively charged surfaces, such as mucosal membranes. The haemostatic effect of HemCon is thought to be due principally to this muco-adhesive property. Unlike QuikClot there are no known harmful effects associated with the use of this dressing, although significant variability of adherence between the manufactured dressings has been observed. Similar dressings also include Celox® and Combat Gauze®.
Two potential (future) alternatives to QuikClot® and HemCon® include the dry fibrin sealant dressing (DFSD) and rapid deployment haemostat (RDH) dressing. These have mostly attracted attention in the USA.
The DFSD is a pliable dressing primarily composed of clotting proteins purified from donated blood and plasma. The mechanism of haemostasis involves the clotting proteins dissolving in plasma and an enzymatic reaction of thrombin with fibrinogen forms a fibrin layer that adheres tightly to the injured tissue. The dressing is not currently available for clinical use, and further studies are required to investigate its efficacy and safety for FDA approval. The RDH dressing is an algae-derived dressing composed of poly-N-acetyl-glucosamine. The proposed mechanisms of haemostasis are thought to include red blood cell aggregation, platelet activation, activation of the clotting cascade activation, and local vasoconstriction via endothelial release. Although the RDH has received FDA approval in the US, it is not yet commercially available.
Tourniquets are increasingly utilized in the pre-hospital environment in order to arrest bleeding distal to the point of application, although considerable controversy exists about their safety and efficacy. However, the relative risk to the limb is outweighed by the likely risk of death from severe exsanguination.
Internal (non-compressible) haemorrhage
Where haemorrhage cannot be controlled externally, initial management should include a cautious approach with regard to fluid resuscitation in order to avoid rapid rises in blood pressure that may fragment established clot and cause re-bleeding. However, signs of hypovolaemic shock must be treated in order to restore adequate perfusion. This is even more important in the presence of severe traumatic brain injury where higher mean arterial blood pressures are required to ensure adequate cerebral flow and limit secondary brain injury.
Internal haemorrhage will almost certainly require urgent surgical intervention to achieve haemostasis. Senior clinical decision making is the key to ensuring that patients requiring rapid and safe transfer to theatre are recognized and managed appropriately. Early recognition is vital and the use of imaging techniques such as FAST (ultrasound) and CT are a vital component of this.
Fracture haemorrhage control
Haemorrhage from long bone (particularly femoral shaft) and pelvic fractures may be reduced by traction, binding or splinting. The aim is to stabilize the fracture, reduce the available volume into which bleeding can occur (tamponade) and enable the formation of a stable clot.
Angiographic embolization to control pelvic bleeding is potentially beneficial although time-consuming. An alternative technique involves extraperitoneal packing in the operating theatre.
Traumatic coagulopathy occurs due to consumption and dilution of clotting factors, hypothermia, and acidosis—the so called lethal triad. The risk is higher in circumstances of massive haemorrhage and transfusion. The emphasis should therefore be on attempts to predict and prevent coagulopathy, rather than treatment.
Haematological targets for the trauma patient include:
• Haemoglobin >8 g/dL (haematocrit of >35%).
• Platelets >75 × 109/L (>100 × 109/L in severe trauma).
• APTT and PrT <1.5 × normal levels.
• Fibrinogen >1.0g/L.
Recombinant factor VIIa (rFVIIa)
The use of rFVIIa has been described in a number of different clinical scenarios including traumatic or post-surgical coagulopathy refractory to conventional therapy with continued haemorrhage. Despite growing peer-reviewed clinical evidence, it is still not yet licensed in any country for this indication. It is also not an alternative to surgical control of haemorrhage and is by no means a magic bullet. Adequate clotting factors, cryoprecipitate and platelets need to be present for its full effect and both significant acidosis (pH<7.2) and hypothermia reduce rFVIIa activity.
The usual rFVIIa dose regime quoted is 90–100 mcg/kg, repeated once only within the next 2 h if required.
Trauma in the anticoagulated patient
An increasing number of patients are on regular anticoagulant therapy for prophylaxis of thromboembolic disease. Any injury that bleeds will obviously do so more in the anticoagulated patient. This is of most significance in traumatic brain injury. In the context of hypovolaemic shock due to haemorrhage, the emphasis is on rapid reversal of anticoagulation.
In all cases anticoagulant therapy must be stopped immediately and, in cases of major bleeding, prothrombin complex concentrate (e.g. Beriplex®) 25–50 U/kg (or FFP 15–20 mL/kg if PCC is unavailable) followed by vitamin K. PCC may be contraindicated in the presence of DIC and this should be discussed with a senior haematologist.
The primary goal of fluid resuscitation in trauma is to treat hypovolaemic shock in order to ensure adequate perfusion and oxygen delivery to the tissues. Secondary goals of fluid resuscitation are to attempt to modify the immunological responses to trauma and aid haemostasis.
Permissive hypotension is a resuscitation technique that attempts to limit blood loss until haemostasis has been achieved, although the risk and benefits of tissue hypoperfusion versus further bleeding have to be assessed for each individual patient. This technique is best suited to young patients without co-morbidities, but is contraindicated in the presence of traumatic brain injury.
Resuscitation fluids, including blood, should be warmed prior to administration to reduce further heat loss. The lethal triad of hypothermia, acidosis, and coagulopathy must be avoided in severe trauma as this situation is almost universally associated with a poor outcome.
Use of blood products
Blood loss is commonly under estimated and haemoglobin and haematocrit values do not fall until several hours after acute haemorrhage.
Blood transfusion should not be used to expand vascular volume when oxygen carrying capacity is adequate. Blood transfusion is likely to be required when 30–40% of mean normal blood volume (MNBV, around 70–80 mL/kg body weight) has been lost. Blood products may also be necessary to replace deficient coagulation factors.
Transfusion protocols based upon packed red cell: fresh frozen plasma (PRC:FFP) ratios of 1:1 or 2:1, as well as PRC/FFP/platelet ratios of 1:1:1, have been suggested in situations where massive transfusion is likely on the premise that proactive transfusion management may avoid traumatic coagulopathy. Cryoprecipitate may also be required. The key to the best use of blood products in trauma is timely and effective communication with local blood bank and haematology speciality services, which works best in the presence of an established massive transfusion protocol.
Full ABO group and cross-match takes up to 45 min to complete. In urgent cases, just ABO and Rhesus group compatibility can be tested more rapidly, although this may still take up to 10–15 min. An antibody screen is then performed retrospectively. Further cross-matching is not required after replacement of one full MNBV.
In life-threatening haemorrhage, where there is established need for immediate blood transfusion before type specific or cross-matched blood is available, group O Rh D-positive blood may be used. Due to limited supplies, group O Rh D-negative blood is usually reserved for pre-menopausal females to avoid haemolytic disease of the newborn in future pregnancies.
Issues and possible complications
Rapid transfusion may result in hyperkalaemia, hypothermia, impaired clotting, and citrate toxicity causing hypocalcaemia. Metabolic alkalosis may occur as citrate is metabolized to bicarbonate. Bacterial contamination of donor blood may result in rapid development of severe sepsis. Elderly patients are more susceptible to fluid overload and cardiac failure, and may require diuretic therapy during, or following, blood transfusion. Stored blood will have impaired oxygen delivery characteristics due to leftward shift of the oxyhaemoglobin dissociation curve as a result of inactivity of 2,3-DPG in the first 24 h. Red cell viability is around 70% at 24 h post-transfusion. Coagulation factor activity in PRC solution is negligible and dilutional thrombocytopenia is to be anticipated during massive blood replacement.
• immediate haemolysis due to ABO incompatibility;
• anaphylaxis may occur rarely but can be fatal;
• transfusion-associated acute lung injury (TRALI).
• febrile non-haemolytic transfusion reactions (FNHTR) and delayed haemolysis;
• urticarial reactions from donor plasma proteins.
Risk of infection
In the UK, donor blood is currently screened for hepatitis B, hepatitis C, HIV, syphilis, HTLV-1, and CMV (for selected recipients). Variant Creutzfeld-Jakob disease (vCJD) risks are thought to be extremely low.
Risk of transmission (per unit transfused):
• Hepatitis B = 1 in 100,000–400,000
• Hepatitis C = 1 in 200,000
• HIV = 1 in 4 000,000
Packed red cell (or red cell concentrate) units and platelets are stored at 2–6°C. FFP and cryoprecipitate require thawing for around 30–40 min before use. PRC units left unrefrigerated for more than 30 min should be transfused within 4 h or discarded.
Massive haemorrhage may be defined as:
• Loss of 100% of MNBV in 24 h.
• Loss of 50% of MNBV in 3 h.
• Loss of >150mL/min (externally or into drains).
Despite limited evidence, the early use of cryoprecipitate, FFP and platelets may be beneficial and improve survival. Improved survival in massively transfused patients is also associated with more effective and efficient rewarming techniques and aggressive resuscitation. The use of a massive transfusion protocol to activate a pre-determined sequence of events, supply appropriate blood products and monitor their use is recommended.
In physiological terms, the most ideal resuscitation fluid to use for treating haemorrhagic shock would be fully cross-matched fresh whole blood, restoring haemoglobin, clotting factors, and plasma volume. The risk of transmitting infection means that stored blood products are generally used instead. For this reason intravenous fluids (electrolytes or plasma replacement) are generally the first choice for initial resuscitation until haemostasis is achieved and blood product administration becomes available, if required.
Intravenous fluid solutions may be broadly divided into two groups: electrolyte (crystalloid) solutions, and plasma or plasma substitutes (colloid). Hypertonic sodium chloride solutions are discussed separately. The choice of which fluid to use for resuscitation of the trauma patient remains a highly controversial issue and depends upon several factors, logistical and clinical:
• Unit cost and shelf life.
• Potential allergenicity.
• Duration in intravascular space.
• Immunomodulatory effects.
From a research perspective, hypertonic sodium chloride solutions may offer some important immunomodulatory benefits over other fluids. Although there have been promising clinical results in head-injured patients, the role of these solutions for routine volume replacement in all trauma patients is as yet unproven.
Isotonic solutions may be safely infused via a peripheral venous cannula. Hypertonic solutions are best infused through central venous lines, although they may still be administered peripherally in emergency situations.
The intraosseous route of administration is becoming increasingly common in trauma patients and may be considered a safe route for all isotonic solutions, including plasma and plasma substitutes. However, research into the intra-osseous route for hypertonic solutions has demonstrated a significant risk of local complications including myonecrosis in some animal models. Further research is required before hypertonic solutions are recommended for administration by the intraosseous route in humans.
Electrolyte solutions contain relatively small molecules that may readily pass through capillary and glomerular membranes, but not cell membranes. Cell membrane pumps subsequently alter the distribution of ions. As a result, electrolyte solutions usually remain within the intravascular space for up to 30 min, after which only around 25% of the infused solution is left.
Electrolyte solutions have advantages over plasma replacement solutions by the absence of allergenicity or coagulation dysfunction. Both electrolytes and plasmas are relatively cheap and plentiful with a good shelf life. The main disadvantages of electrolyte solutions are that they are short-lived in the circulation with risk of pulmonary and cerebral oedema from fluid overload. This fluid shift into the interstitial space is further promoted by increased capillary permeability and decreased intravascular colloid oncotic pressure seen as a result of normal physiological responses to trauma.
Most electrolyte solutions are supplied in 500- or 1000-mL bags, except for bicarbonate 8.4%.
Sodium chloride 0.9%
• 150 mmol/L sodium;
• 150 mmol/L chloride.
• Specific indications:
• diabetic ketoacidosis.
• Cautions and complications:
• sodium accumulation;
• hyperchloraemic acidosis;
• fluid overload.
Glucose 5% or 10%
• 5% solution = 50 g/L dextrose;
• 10% solution = 100 g/L dextrose.
• Specific indications:
• free water replacement;
• Cautions and complications:
• peripheral venous irritation and thrombophlebitis;
• disturbances of glucose control in diabetics.
Hartmann’s/Ringer lactate solution
• 131 mmol/L sodium;
• 111 mmol/L chloride;
• 29 mmol/L bicarbonate (as lactate);
• 5 mmol/L potassium;
• 2 mmol/L calcium.
• Specific indications: water and electrolyte replacement.
• Cautions and complications:
• requires normal hepatic function to metabolize lactate to bicarbonate;
• fluid overload.
Sodium bicarbonate is supplied in two main forms:
• 1.26% (150mmol/l each of sodium and bicarbonate).
• 8.4% (1000mmol/l each of sodium and bicarbonate).
The 1.26% form is usually supplied in either 500- or 1000-mL bags for infusion. The 8.4% solution comes in 10- or 50-mL minijet® containers and is generally reserved for slow injection in emergency situations.
• Specific indications:
• severe metabolic acidosis (ph <7.1);
• emergency treatment of hyperkalaemia;
• prolonged cardiac arrest;
• tricyclic antidepressant toxicity.
• Cautions and complications:
• high osmolar load (8.4% solution);
• may exacerbate intracellular acidosis.
Constituents of potassium containing solutions vary depending upon the solution used with potassium concentrations being either 0.15% (20 mmol/L) or 0.3% (40 mmol/L). Pre-prepared bags of fluid are typically made up with glucose 5% or sodium chloride 0.9%.
• Specific indications: hypokalaemia.
• Cautions and complications:
• inadvertent hyperkalaemia;
• rapid infusion may cause cardiac toxicity.
Plasma and plasma substitutes
Plasma and plasma substitutes vary substantially in their pharmacology and pharmacokinetics. Molecules with a molecular weight of less than 50,000 D will readily pass through the glomerular membrane and be excreted, although still less rapidly than any electrolyte solutions.
Synthetic colloids are now widely accepted as an effective alternative to human albumin for volume replacement in trauma patients. Most plasma solutions are supplied in 500- or 1000-mL bags, except for human albumin solution (HAS) and Haemaccel®, which are supplied in bottles.
Human albumin solution from 4.5–25%
HAS consists of naturally occurring albumin, derived from pooled human plasma by fractionation, with a molecular weight of around 69,000 D. HAS is heated and sterilized by ultrafiltration and is generally accepted to have a very low risk of transmission of infectious diseases.
In addition to its colloid properties, albumin also proffers some theoretical advantages from its involvement in plasma molecular carriage, coagulation, and membrane integrity, as well as being a free radical scavenger.
• 4.5% solution = 45 mg/mL human albumin.
• 5.0% solution = 50 mg/mL human albumin.
• 20% solution = 200 mg/mL human albumin.
• 25% solution = 250 mg/mL human albumin.
Usually supplied in 50-, 100-, 250-, 400-, or 500-mL bottles (for isotonic solutions) and 20-, 50-, or 100-mL bottles (for hypertonic solutions).
• Specific indications:
• replacement of plasma volume losses, e.g. burns;
• Cautions and complications:
• despite its theoretical advantages, HAS is yet to be proven in clinical practice, although careful use may be beneficial in some trauma patients;
• the incidence of serious adverse reactions following the use of HAS is around 1:30 000
Gelatin solution is a generic term applied to the three main proprietary solutions each containing a different mixture of solutes. All gelatin solutions have an average molecular weight of 30,000 D (compared with around 69,000 D for human albumin). Although derived from beef, gelatin solutions are generally agreed to be free of risk of prion transmission.
• Gelofusine® (Braun):
• 4% (40g/L) succinylated bovine gelatine;
• 154 mmol/L sodium;
• 120 mmol/L chloride;
• 0.4 mmol/L each of potassium, calcium, and magnesium.
• Haemaccel® (KoRa):
• 3.5% (35g/L) polygeline;
• 145 mmol/L sodium;
• 145 mmol/L chloride;
• 5.1 mmol/L potassium;
• 6.25 mmol/L calcium.
• Volplex® (Maelor):
• 4% (40g/L) succinylated gelatine;
• 154 mmol/L sodium;
• 125 mmol/L chloride.
• Specific indications: plasma volume replacement.
• Cautions and complications:
• the incidence of serious adverse reactions following the use of Gelofusine® is around 1:13,000;
• relatively short intravascular half-life (approximately 2 h).
These are high polymeric glucose compounds manufactured through hydrolysis and hydroxyethylation from >90% amylopectin. Also referred to as hydroxyethyl starches (HES).
Two main non-proprietary solutions are available, both of which are presented in sodium chloride 0.9% solution:
• Hetastarch (450,000 D) 6%.
• Pentastarch (200,000 D) 6% or 10%.
Voluven® (Fresenius Kabi) is a proprietary form of tetra-starch (130,000 D) 6% and, like the other starch solutions, is also presented in sodium chloride 0.9% solution.
• Specific indications: plasma volume replacement.
• Cautions and complications:
• HES will accumulate, although <1% of the total dose will remain in the body after 2 weeks;
• the incidence of serious adverse reactions following the use of Hetastarch is around 1:16,000.
Hypertonic solutions (HS)
There is an increasing enthusiasm for the use of HS in the treatment of hypovolaemic shock in trauma patients. Several cardiovascular advantages are believed to be conferred including:
• Displacement of fluid into intravascular compartment
• Vasodilatory effects on pulmonary vasculature
• Direct positive inotropic effects on myocardium
Other potential advantages include the fact that only small volumes of HS are necessary to achieve the same desired effect of isotonic solutions, thereby less chance of fluid overload and also smaller volumes needed to be carried by pre-hospital personnel.
Various concentrations of HS are available, both alone and in combination with other fluids. Individual vials of sodium chloride are also supplied in 3, 5, 7.5, and 10% strengths, and their use is generally limited to critical care management of severe head injury. The most commonly used combined hypertonic sodium chloride solutions include:
• RescueFlow® (Vitaline): 250 mL sodium chloride 7.5%, containing 6% dextran 70 (70,000 D).
Dextrans are glucose polymers available in different molecular weights preparations. Negative adverse effects of dextrans solutions include coagulation abnormalities and severe life-threatening hypersensitivity reactions.
• HyperHAES® (Fresenius Kabi): 250 mL sodium chloride 7.2%, containing 6% hydroxyethyl (tetra-) starch (200,000 D).
• Specific indications:
• traumatic brain injury;
• low volume resuscitation of trauma patients.
• Cautions and complications:
• the incidence of serious adverse reactions following the use of Dextran 70 is around 1:4500;
• effects of HS alone are reported to be transient;
• limited number of clinical trials for high dose HS.
Although still at an experimental stage, haemoglobin and synthetic oxygen carrier solutions may have a potential future role in the management of trauma patients.
• Stroma-free haemoglobin (SFH).
• Micro-encapsulated haemoglobin (neo red cells).
• Chelating agents.
• Perfluorocarbons (PFCs).
The advantages of such products include minimal infection risk, no need for cross-matching, long shelf life, and easier storage at ambient temperature. Of these, haemoglobin-based oxygen carriers (HBOCs) and PFC emulsions are the most likely candidates for general clinical use.
In the context of trauma, shock is generally the result of hypovolaemia due to haemorrhage. Other causes of shock may be directly related to trauma, or may develop following trauma. These may be recognized immediately, or may present later during the initial management of the injured patient.
Other causes of shock are:
• Non-haemorrhagic hypovolaemic shock
• Cardiogenic shock, including:
• intrinsic cardiogenic shock;
• obstructive cardiogenic shock;
• distributive shock, including:
• neurogenic shock;
• septic shock;
• anaphylactic shock.
Non-haemorrhagic hypovolaemic shock
Non-haemorrhagic hypovolaemic shock can occur in the injured patient and may be especially relevant where the circumstances or environment predispose to greater fluid losses, such as a lengthy entrapment or crush injury. An increase in fluid losses may be due to several medical conditions and may develop as a complication of the injury, or could even be responsible for the injury itself.
Non-haemorrhagic hypovolaemia can occur due to uncompensated fluid volume loss, from extravascular fluid sequestration (third spacing) of intravascular fluid or following burns. Causes of increased fluid loss include burns, crush injury, and pancreatitis.
Intravascular and interstitial compartments are usually held in equilibrium, with losses from one resulting in passage of fluid from the other. Losses of interstitial fluid volume will therefore lead to a reduction in intravascular volume and subsequent shock.
Head injury may result in a deficiency of ADH (vasopressin) production due to hypothalamic or pituitary damage. Termed neurogenic (or cranial) diabetes insipidus, this condition is characterized by excretion of large amounts of highly diluted urine, which will lead to hypovolaemia if untreated. This process may take a few days to develop and in head injury may be temporary, often recovering within a few weeks.
Third spacing of intravascular fluid may occur due to post-traumatic pancreatitis or following injury to the liver or bowel. Increased renal losses of protein from nephrotic syndrome can also lead to increased third spacing.
The diagnosis of non-haemorrhagic hypovolaemic shock should only be made by exclusion in the injured patient.
The management of hypovolaemic shock should focus on treating the cause of the volume loss. This will usually only require the replacement of water deficit and restoration of appropriate electrolyte balance. Neurogenic diabetes insipidus can be treated with the vasopressin analogue, desmopressin, although mild cases may be managed appropriately with increased fluid intake alone.
Cardiogenic shock can occur in a susceptible patient due to the physiological stress of the traumatic event. Patients may also present with trauma that has occurred as a direct consequence of a primary cardiac event, such as a myocardial infarction causing arrhythmia and loss of consciousness while driving.
Cardiogenic shock may be divided into intrinsic or extrinsic causes and may co-exist in trauma patients. Intrinsic causes are due to insufficient ejection fraction and cardiac output despite adequate intravascular volume and cardiac filling. Relevant intrinsic causes include myocardial infarction or contusion, traumatic valvular, or ventricular defects, arrhythmias due to ischaemia or toxins, and pre-existing cardiomyopathy.
Extrinsic causes are either due to obstruction of venous return or from external compression preventing adequate cardiac filling and stroke volume. Causes include:
• Tension pneumothorax.
• Cardiac tamponade.
• Mediastinal haemorrhage or pneumo-mediastinum.
• Massive pulmonary embolus.
• Diaphragmatic hernia.
• Positive pressure ventilation.
The most important traumatic causes of cardiogenic shock include cardiac contusion from blunt thoracic trauma, cardiac tamponade from penetrating injury or tension pneumothorax.
The most common cause of cardiogenic shock is acute myocardial infarction, leading to a marked decrease in myocardial contractility, reducing the ejection fraction and thereby cardiac output. Cardiogenic shock usually involves some degree of left ventricular dysfunction. Decom-pensation may occur as a result of falling arterial pressure with the subsequent exacerbation of myocardial ischaemia. The heart rate usually increases to compensate for hypotension, exacerbating myocardial oxygen demand.
Direct injury to the heart may result in rupture to the ventricular wall resulting in a pericardial haematoma and cardiac tamponade, valvular rupture reducing forward flow and ejection fraction, or ventricular contusion reducing myocardial contractility.
A tension pneumothorax causes a rise in intrathoracic pressure and may reduce cardiac output. Injury to the mediastinum may result in increased pressure exerted upon the pericardial space and an indirect tamponade effect. The use of positive pressure ventilation, especially when using higher positive end expiratory pressures (PEEP), may also reduce cardiac filling due to the increase in intrathoracic pressure.
Pulmonary embolus is unlikely to present early as a result of trauma, although it may be a later complication. A large pulmonary embolus will obstruct blood flow returning to the left ventricle and thus cause a reduction in cardiac output.
Cardiogenic shock is more likely to occur in the elderly and those with known cardiac disease. A history of previous myocardial infarction and atherosclerotic disease increases the likelihood of developing cardiogenic shock.
All forms of cardiogenic shock lead to a fall in cardiac output and a rise in systemic vascular resistance. Central venous pressure is generally increased in cardiogenic shock, although the true CVP falls due to tension pneumothorax from reduced venous return. The CVP may appear falsely raised, reflecting the intrapleural rather than vascular pressure.
ECG complexes may appear small in the presence of a pericardial effusion large enough to result in tamponade.
The specific management of cardiogenic shock should focus on treating the cause, particularly in obstructive shock and myocardial infarction, which may include urgent reperfusion therapy in appropriate cases.
The general approach to managing intrinsic cardiogenic shock is to optimize oxygen delivery and left ventricular filling pressures. Fluid resuscitation may be necessary where there are signs of hypotension due to poor cardiac filling. Inotropic and vasodilator therapy may be used with signs of raised left ventricular filling pressures, such as pulmonary oedema. Typical drug therapy involves the use of oxygen, opiates, nitrates, and diuretics. Inotropic agents include dobutamine, which increases myocardial contractility while reducing left ventricular end-diastolic pressure.
The approach to managing obstructive shock involves the restoration of cardiac filling and stroke volume by the removal of external compression forces (in the case of tension pneumothorax for example) or of internal vascular obstruction from pulmonary embolus. In the case of tension pneumothorax, immediate needle decompression is required initially followed by tube thoracostomy. Cardiac tamponade usually requires emergency surgical removal of clotted blood by thoracotomy.
Distributive causes of shock
Distributive shock is the term applied to shock caused by rapid shifts in fluid distribution. Hypotension occurs either as the result of vasodilatation and capillary leakage due to the inflammatory responses of sepsis and anaphylaxis, or may be due to loss of peripheral sympathetic vasopressor tone in the case of neurogenic shock.
Of the three distributive causes, neurogenic shock must be recognized and differentiated from hypovolaemic shock as soon as possible during the management of the trauma patient. Spinal cord injury may rapidly produce hypotension due to a loss of peripheral sympathetic vasopressor tone, and an absence of the normal tachycardia response in the case of high spinal cord injury. However, signs of neurogenic shock should be initially managed as if due to hypovolaemia, as patients who have sustained severe spinal injuries often have co-existing thoracic, abdominal or pelvic injuries. Neurogenic shock may mask the normal physiological response to hypovolaemia. Associated head injury occurs in about 25% of spinal cord injury patients.
Neurogenic shock occurs in spinal injuries above the T6 level and is secondary to the loss of normal sympathetic autonomic outflow below T1. This results in a loss of systemic vascular resistance due to interruption in normal vascular smooth muscle (vasoconstrictor) tone.
The release of catecholamines immediately following a spinal injury may maintain a partial pressor response and therefore the signs of neurogenic shock may take a few minutes to hours to appear.
The dominating presenting feature of all causes of distributive shock is due to the loss of systemic vascular resistance. Central venous pressure is often unaffected, unless there is concurrent cause for hypovolaemia, and cardiac output may remain the same or elevated. A spinal injury level above T6 is characterized by hypotension and, above T1, additionally by bradycardia, due to unopposed vagal tone.
It is important to exercise caution when dealing with trauma patients with signs of spinal shock as there may also be evidence of hypovolaemic shock requiring urgent surgical intervention. The hypovolaemic trauma patient on ß-blocker therapy may show appearances consistent with an apparent spinal injury.
Where the injury mechanism and clinical signs suggest spinal shock, and there are no signs of a hypovolaemic cause, initial management relies on optimizing oxygen delivery and sufficient fluid volume resuscitation to fill the expanded intravascular space. Subsequent management may require use of an appropriate vasopressor, such as noradrenaline, dopamine, or phenylephrine. Regular bolus therapy with the vasopressor metaraminol may be useful while waiting for an infusion to be commenced. A haemodynamically significant bradycardia may be treated with atropine 500-mcg aliquots up to 3 mg intravenously.
Sepsis is a rare early cause of shock in the injured patient, although it may occur following trauma if there has been sufficient delay before presentation. Sepsis may be defined as the presence of the Systemic Inflammatory Response Syndrome (SIRS) with an established source of infection. Septic shock is defined as hypotension, or the requirement for inotropic support despite adequate fluid resuscitation associated with sepsis. SIRS criteria defined as two or more of:
• Hypothermia (<36°C) or hyperthermia (>38°C).
• Tachycardia (heart rate >90/min).
• Tachypnoea (>20/min).
• Leucopenia (<4 × 109/L) or leucocytosis (>12 × 109/L).
As can be seen, these criteria do not differentiate the process, as trauma itself will result in a SIRS clinical state. Therefore, these features cannot be relied upon alone to diagnose or exclude sepsis as a cause for shock.
The main causes of sepsis from trauma include translocation of bacteria and endotoxins across the gut wall into the systemic circulation either due to splanchnic hypoperfusion as a result of hypovolaemic shock or from local bowel wall perforation, wound infections, and aspiration of gastric contents.
The release of inflammatory mediators into the circulation causes a loss of systemic vascular resistance, venous pooling, reduced venous return, and thereby a fall in cardiac output. Hypovolaemia then follows, causing a further reduction in central venous pressure and cardiac pre-load and subsequently cardiac output. Eventually, falling arterial blood pressure leads to myocardial ischaemia producing a superimposed intrinsic cardiogenic shock.
Most cases of sepsis are due to bacterial sources, traditionally due to Gram-negative organisms, such as E. coli, although Gram-positive organisms are increasingly being implicated (including streptococci and staphylococci). Contributory factors include a loss of immune function due to concomitant therapy or from splenectomy.
• SIRS clinical state;
• hyperdynamic circulation with reduced SVR;
• metabolic (lactic) acidosis;
• reduced oxygen extraction and utilization;
• multiple organ dysfunction.
• acute renal and hepatic failure;
• pancreatitis and diabetes mellitus;
• Acute Respiratory Distress Syndrome (ARDS);
• disseminated intravascular coagulation (DIC);
• Cardiac failure.
Initial management is supportive with appropriate oxygen therapy and fluid resuscitation. Inotropic and vasopressor therapy will be required in the presence of organ dysfunction secondary to ongoing hypoperfusion despite adequate fluid resuscitation. Antibacterial therapy must be instituted as early as possible and the choice of drug must be based upon the most likely causative organism and modified by the results of culture from suitable body fluid and tissue samples. Ideally, such samples should be taken before antibiotic therapy is started. Treatment may also require the use of antiviral or antifungal agents, as guided by culture results.
Early surgical care, including wound debridement and drainage of infected tissue or pus collections will be required to treat the underlying source.
The severe sepsis bundles are a distillation of the evidence-based recommendations from the Surviving Sepsis Campaign and wider critical care community. These are designed to allow medical teams to follow the appropriate timing, sequence, and goals of individual elements in the care of septic patients.
True anaphylaxis occurs when a pre-sensitized individual is exposed to a known allergen. Typical features are of a sudden onset and rapid progression with potentially life-threatening airway, breathing, and circulatory problems. Although not usually directly related to the mechanism of injury, anaphylaxis in a trauma patient may occur as the result of treatment administered during resuscitation. Causative agents include antibiotics, intravenous colloids and anaesthetic induction agents, such as thiopentone.
Anaphylaxis is a Type I immune reaction, which is characterized by the release of various vasoactive substances (particularly histamine) and results from an antigen-antibody reaction on the surface of mast cells. Release of these substances causes angioedema, as well as vasodilatation with increased capillary permeability and myocardial depression, resulting in shock.
• Angioedema with pharyngeal or laryngeal oedema.
• Vasodilation and subsequent hypotension.
• Cutaneous erythema and urticaria.
American College of Surgeons Committee on Trauma. Advanced Trauma Life Support, Student Course Manual (6th Ed). New York: ACS, 1997.Find this resource:
Bilkovski RN, Rivers EP, Horst HM. Targeted resuscitation strategies after injury. Curr Opin Crit Care 2004; 10: 529–38.Find this resource:
Boffard K, Riou B, Warren B, Choong P, Rizoli S, Rossaint R, et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma: Injury Infect Crit Care 2005; 59(1): 8–18.Find this resource:
Borgman M, Spinella P, Perkins J, Grathwohl K, Repine T, Beekley A, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007; 63: 805–13.Find this resource:
Holcomb JB, et al. Damage control resuscitation: directly addressing the coagulopathy of trauma. J Trauma 2007; 62: 307–10.Find this resource:
Mannucci PM, Levi M. Prevention and treatment of major blood loss. N Engl J Med 2007; 356: 2301–11.Find this resource:
Nguyen HB, Rivers EP, Abrahamian FM, Moran GJ, Abraham E, Trzeciak S, et al. Emergency Department Sepsis Education Program and Strategies to Improve Survival (ED-SEPSIS) Working Group. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Annl Emerg Med 2006; 48>: 28–54.Find this resource:
NICE (2002) Central Venous Catheter—Ultrasound Locating Devices. London: NICE.Find this resource:
Pinnock C, Lin T, Smith T (eds). Fundamentals of Anaesthesia, 2nd edn. Greenwich: Medical Media, 2003.Find this resource:
Smith JE, Hall MJ. Hypertonic Saline. J Roy Army Med Corps 2004; 150: 239–43. Available at: http://www.survivingsepsis.org/Find this resource:
Spahn D. Editorial: Is recombinant FVIIa the magic bullet in the treatment of major bleeding? Br J Anaesthes 2005; 94(5): 553–5.Find this resource:
T J Hodgetts, P F Mahoney, et al. ABC to <C>ABC: redefining the military trauma paradigm. EMJ 2006; 23: 745-746.Find this resource:
W Sapsford. A role for recombinant activated factor VII in trauma? Trauma 2002; 4: 117.Find this resource:
Yentis SM, Hirch NP, Smith GB. (eds) Anaesthesia and Intensive Care A–Z,. 3rd edn. Amsterdam: Elsevier, 2004.Find this resource:
Zalstein S, Pearce A, Scott D, Rosenfeld J. Damage control resuscitation: a paradigm shift in the management of haemorrhagic shock. Emerg Med Aust 2008; 20: 291–3.Find this resource: