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Carl Waldmann

, Andrew Rhodes

, Neil Soni

, and Jonathan Handy

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date: 22 April 2021

Chapter contents

Basic and advanced resuscitation

The interventions that contribute to a successful outcome after a cardiac arrest are conceptualized as a chain—the ‘Chain of Survival’:

  • Early recognition and call for help.

  • Early cardiopulmonary resuscitation (CPR).

  • Early defibrillation.

  • Postresuscitation care.


  • In-hospital cardiac arrests are usually neither sudden nor unpredictable; in ~80% there is deterioration in clinical signs during the preceding few hours.

  • The cardiac arrest rhythm is usually pulseless electrical activity (PEA) or asystole, and prognosis is poor.

  • Earlier recognition (e.g. early warning scoring systems) and treatment can prevent some cardiac arrests, deaths, and unanticipated intensive care unit (ICU) admissions.

  • Implementation of rapid response systems reduces the incidence of cardiac arrest.

  • Earlier recognition enables an emergency care and treatment plan to be agreed; this may include a do not attempt cardiopulmonary resuscitation (DNACPR) decision.

In-hospital resuscitation

After in-hospital cardiac arrest, the division between basic life support (BLS) and advanced life support (ALS) is arbitrary; in practice, in-hospital resuscitation is a continuum. For all in-hospital cardiac arrests, ensure that:

  • Cardiorespiratory arrest is recognized immediately.

  • Help is summoned using a standard telephone number—it should be 2222 in the UK.

  • CPR is started immediately and, if indicated, defibrillation is attempted as soon as possible (within 3 min at the most).

Risks to the rescuer

  • There are few reports of harm to rescuers from doing CPR.

  • Wear gloves. Eye protection, aprons, and face masks may be necessary.

  • Infection risk is lower than perceived. There are reports of infections with tuberculosis and severe acute respiratory distress syndrome. Human immunodeficiency virus transmission has never been reported.

High-quality cardiopulmonary resuscitation

Chest compressions generate bloodflow by increasing intrathoracic pressure and compressing the heart directly; however, perfusion of the brain and myocardium is, at best, 25% of normal. The CPR must be of the highest quality to optimize the chances of survival. The characteristics of high-quality chest compressions include:

  • Depth of 5–6 cm.

  • Rate of 100–120 compressions/min.

  • Full chest recoil after each compression.

  • The same time for compression and relaxation.

  • Minimal interruptions to chest compression (hands-off time).

Advanced life support

Adapted, with permission, from Advanced Life Support 7th Edition, the Resuscitation Council (UK).

The ALS algorithm enables a standardized approach to cardiac arrest management. Cardiac arrest rhythms are classified as:

  • Shockable rhythms—ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). The first monitored rhythm is VF/pVT in approximately 20% of cardiac arrests, both in-hospital or out-of-hospital. VF/pVT will also occur at some stage during resuscitation in about 25% of cardiac arrests with an initial documented rhythm of asystole or PEA.

  • Non-shockable rhythms—asystole and PEA.

Treatment of shockable rhythms (VF/pVT)

Further details about defibrillation can be found in the section on ‘Temporary cardiac pacing’ in Chapter 2.

  1. 1. Confirm cardiac arrest—check for normal breathing and pulse simultaneously.

  2. 2. Call resuscitation team.

  3. 3. Perform uninterrupted chest compressions while applying self-adhesive defibrillation/monitoring pads—one below the right clavicle and the other in the V6 position in the mid-axillary line.

  4. 4. Plan actions before pausing CPR for rhythm analysis and communicate these to the team.

  5. 5. Stop chest compressions; confirm VF/pVT from the electrocardiograph (ECG). This pause in chest compressions should be brief and no longer than 5 s.

  6. 6. Resume chest compressions immediately; warn all rescuers other than the individual performing the chest compressions to ‘stand clear’ and remove any oxygen delivery device as appropriate.

  7. 7. The designated person selects the appropriate energy and charges the defibrillator. Use at least 150 J for the first shock and the same or a higher energy for subsequent shocks, or follow the manufacturer’s guidance for the particular defibrillator.

  8. 8. Ensure that the rescuer giving the compressions is the only person touching the patient.

  9. 9. Once the defibrillator is charged and the safety check is complete, tell the rescuer doing the chest compressions to ‘stand clear’; when clear, give the shock.

  10. 10. After shock delivery immediately restart CPR using a ratio of 30:2, starting with chest compressions. Do not pause to reassess the rhythm or feel for a pulse. This pause in chest compressions should be brief and no longer than 5 s.

  11. 11. Continue CPR for 2 min; the team leader prepares the team for the next pause in CPR.

  12. 12. Pause briefly to check the monitor.

  13. 13. If VF/pVT, repeat steps 6–12 and deliver a second shock.

  14. 14. If VF/pVT persists, repeat steps 6–8 and deliver a third shock. Resume chest compressions immediately. Give intravenous (IV) adrenaline 1 mg and amiodarone 300 mg IV while performing a further 2 min CPR. Withhold adrenaline if there are signs of return of spontaneous circulation (ROSC) during CPR.

  15. 15. Repeat this 2 min CPR—rhythm/pulse check—defibrillation sequence if VF/pVT persists.

  16. 16. Give further adrenaline 1 mg IV after alternate shocks (i.e. approximately every 3–5 min).

  17. 17. If organized electrical activity compatible with a cardiac output is seen during a rhythm check, seek evidence of ROSC (check for signs of life, a central pulse, and end-tidal CO2 [ETCO2] if available).

    1. a. If there is ROSC, start postresuscitation care.

    2. b. If there are no signs of ROSC, continue CPR and switch to the non-shockable algorithm.

  18. 18. If asystole is seen, continue CPR and switch to the non-shockable algorithm.

    • Minimize the interval between stopping compressions and delivering a shock. Longer interruptions to chest compressions may reduce the chance of a shock restoring a spontaneous circulation. Chest compressions are resumed immediately after delivering a shock (without checking the rhythm or a pulse). The first dose of adrenaline is given during the 2-min period of CPR after delivery of the third shock.

    • Give amiodarone 300 mg after three defibrillation attempts. Do not stop CPR to check the rhythm before giving drugs unless there are clear signs of ROSC.

    • Subsequent doses of adrenaline are given after alternate 2-min loops of CPR (which equates to every 3–5 min) for as long as cardiac arrest persists. If VF/pVT persists, or recurs, a further dose of 150 mg amiodarone may be given after a total of five defibrillation attempts.

    • When the rhythm is checked 2 min after giving a shock, if a non-shockable rhythm is present and the rhythm is one that could be compatible with a pulse, try to palpate a central pulse and look for other evidence of ROSC (e.g. sudden increase in ETCO2 or evidence of cardiac output on any invasive monitoring equipment). If there is any doubt about the presence of a palpable pulse, resume CPR. If the patient has ROSC, begin postresuscitation care. If the patient’s rhythm changes to asystole or PEA, see non-shockable rhythms as discussed.

Precordial thump

  • A precordial thump has a very low success rate for cardioversion of a shockable rhythm; do not use it routinely.

  • Consider a precordial thump only when it can be used without delay whilst awaiting the arrival of a defibrillator in a monitored VF/pVT arrest.

Witnessed and monitored VF/pVT cardiac arrest

If a patient has a monitored and witnessed cardiac arrest (typically in a high-care area) and a manual defibrillator is rapidly available:

  • Confirm cardiac arrest and shout for help.

  • If the initial rhythm is VF/pVT, give up to three quick successive (stacked) shocks.

  • Rapidly check for a rhythm change and, if appropriate, check for a pulse and other signs of ROSC after each defibrillation attempt.

  • Start chest compressions and continue CPR for 2 min if the third shock is unsuccessful.

If this initial three-shock strategy is unsuccessful for a monitored VF/pVT cardiac arrest, follow the ALS algorithm and treat these three shocks as if only the first single shock has been given. These initial three stacked shocks are considered as giving the first shock in the ALS algorithm, i.e. the first dose of adrenaline should be given after another two shock attempts if VF/pVT persists.

Treatment for PEA and asystole

  • Start CPR 30:2.

  • Give adrenaline 1 mg IV/intraosseous (IO) as soon as intravascular access is achieved.

  • Continue CPR 30:2 until the airway is secured—then continue chest compressions without pausing during ventilation.

  • Recheck the rhythm after 2 min.

If electrical activity compatible with a pulse is seen, check for a pulse and/or signs of life:

  • If a pulse and/or signs of life are present, start postresuscitation care.

  • If no pulse and/or no signs of life are present (PEA or asystole):

    • Continue CPR.

    • Recheck the rhythm after 2 min and proceed accordingly.

    • Give further adrenaline 1 mg IV every 3–5 min (during alternate 2-min loops of CPR).

  • If VF/pVT at rhythm check, change to shockable side of algorithm.

Airway and ventilation

  • Many patients on an ICU will already be intubated at the time of cardiac arrest. Tracheal intubation provides the most reliable airway during CPR, but, if a tracheal tube is not already in place, attempts at intubation should be made only by trained personnel.

  • Avoid stopping chest compressions during laryngoscopy and intubation; if necessary, a brief pause in chest compressions may be required as the tube is passed between the vocal cords, but this pause should not exceed 5 s.

  • After intubation, confirm correct tube position with waveform capnography and secure the tube adequately.

  • Once the patient’s trachea has been intubated, continue chest compressions at a rate of 100–120/min without pausing during ventilation.

  • A supraglottic airway device (e.g. i-gel) is an alternative to tracheal intubation.

  • If a supraglottic airway device has been inserted, attempt continuous chest compressions without stopping for ventilations. If gas leakage is excessive, interrupt the chest compressions to enable adequate ventilation.

Monitoring during CPR

Several methods can be used to monitor the patient during CPR and potentially help guide ALS interventions.

  • Clinical signs such as breathing efforts, movements, and eye opening can occur during CPR. These can indicate ROSC but can also occur because high-quality CPR can generate a circulation sufficient to restore signs of life, including consciousness.

  • Pulse checks can be used to identify ROSC when there is an ECG rhythm compatible with a pulse, but may not detect pulses in those with low cardiac output states and a low blood pressure.

  • Monitoring the heart rhythm through pads or ECG electrodes is a standard part of ALS.

  • In critical care settings, invasive arterial pressure monitoring will enable the detection of even very low blood pressure values when ROSC is achieved.

  • ETCO2 measured with waveform capnography has several functions during CPR:

    • Ensuring tracheal tube placement in the trachea. Correct tube placement also relies on observation and auscultation to ensure that both lungs are ventilated.

    • Monitoring ventilation rate during CPR and avoiding hyperventilation.

    • Monitoring the quality of chest compressions during CPR: deeper chest compressions increase ETCO2 values.

    • Identifying ROSC during CPR. An increase in ETCO2 during CPR may indicate ROSC and prevent unnecessary and potentially harmful administration of adrenaline in a patient with ROSC. If ROSC is suspected during CPR, withhold adrenaline. Give adrenaline if cardiac arrest is confirmed at the next rhythm check.

    • Prognostication during CPR. Precise values of ETCO2 depend on several factors, including the cause of cardiac arrest, chest compression quality, and the use of adrenaline. Low ETCO2 values during CPR are associated with lower ROSC rates and increased mortality. ETCO2 values should be considered only as part of a multimodal approach to decision-making for prognostication during CPR.

  • Feedback or prompt devices can monitor CPR quality data such as compression rate and depth during CPR and provide real-time feedback to rescuers.

  • Blood sampling and analysis during CPR can be used to identify potentially reversible causes of cardiac arrest. During cardiac arrest, arterial gas values may bear little relationship to the tissue acid–base state. Analysis of central venous blood may provide a better estimation of tissue pH.

  • Focused echocardiography/ultrasound can be useful for the detection of potentially reversible causes of cardiac arrest (e.g. cardiac tamponade, pulmonary embolism, ischaemia [regional wall motion abnormality], aortic dissection, hypovolaemia, pneumothorax), and low cardiac output states (pseudo-PEA).

    • The integration of ultrasound into ALS requires considerable training if interruptions to chest compressions are to be minimized.

    • Placement of a subxiphoid probe just before chest compressions are paused for a planned rhythm assessment enables a well-trained operator to obtain views within 10 s.

Drug delivery

  • Peak drug concentrations are higher and circulation times shorter when drugs are injected into a central venous catheter compared with a peripheral cannula.

  • On the ICU, a central venous catheter (CVC) is often in situ at the time of cardiac arrest. If not in situ, insertion of a CVC is not an immediate priority—it requires interruption of CPR and is associated with several potential complications.

  • Peripheral venous cannulation is quicker, easier, and safer. Drugs injected peripherally must be followed by a flush of at least 20 ml of fluid and elevation of the extremity for 10–20 s to facilitate drug delivery to the central circulation.

  • If intravenous access is difficult or impossible, consider the IO route. IO injection of drugs achieves adequate plasma concentrations in a time comparable with injection through a vein.

  • The three main insertion sites for IO access recommended for use in adults are the proximal humerus, proximal tibia, and distal tibia.

  • Once IO access has been confirmed, resuscitation drugs, including adrenaline and amiodarone can be infused. Fluids and blood products can also be delivered but pressure will be needed to achieve reasonable flow rates using either a pressure bag or a syringe.

Reversible causes

Identify and treat reversible causes during CPR for all cardiac arrests. This is particularly important in the ICU where potentially reversible causes are more common.

  • Hypoxia.

  • Hypovolaemia.

  • Hyperkalaemia, hypokalaemia, hypocalcaemia, acidaemia, and other metabolic disorders.

  • Hypothermia.

  • Tension pneumothorax.

  • Tamponade.

  • Toxic substances.

  • Thromboembolism (pulmonary embolism or coronary thrombosis).

The use of automated mechanical chest compression devices

Automated mechanical chest compression may enable the delivery of high-quality compressions in circumstances where this is not possible with manual compressions—CPR in a moving ambulance where safety is at risk, prolonged CPR (e.g. hypothermic arrest), and CPR during certain procedures (e.g. coronary angiography or preparation for extracorporeal CPR).

Extracorporeal CPR

  • Venoarterial extracorporeal membrane oxygenation (ECMO) can restore flow of oxygenated blood to patients in cardiac arrest, thus buying time for treatment of reversible underlying conditions and restoration of an adequate spontaneous circulation. This is commonly called extracorporeal life support (ECLS) and, more specifically, extracorporeal CPR (eCPR) when used during cardiac arrest. These techniques have been used for both in-hospital and out-of-hospital cardiac arrest.

  • Observational studies suggest that eCPR is associated with improved survival when there is a reversible cause for cardiac arrest (e.g. myocardial infarction, pulmonary embolism, severe hypothermia, poisoning), there is little comorbidity, the cardiac arrest is witnessed, the individual receives immediate high-quality CPR, and eCPR is implemented within 1 h of collapse.

Postresuscitation care

See Chapter 17.2.


The outcome from out-of-hospital cardiac arrest (OHCA) is slowly improving but still remains relatively poor, with survival to hospital discharge in the UK of 8%. After in-hospital cardiac arrest, the survival to hospital discharge is 18% (50% after VF and 10% after PEA or asystole). The majority of survivors have a good neurological recovery. The outcome from cardiac arrest in a critical care area is better than in other in-hospital locations.

CPR on the ICU

Many aspects of CPR on the ICU are specific to this environment:

  • Most cardiac arrests will be both monitored and witnessed.

  • There should be minimal delay before starting CPR.

  • Many patients are already receiving positive pressure ventilation at the onset of cardiac arrest.

  • Mechanical ventilation can be continued during chest compressions, but the airway pressure alarms will be distracting and, if a pressure mode is being used, inadequate tidal volumes will be given.

  • Continuous invasive arterial pressure monitoring is frequently in place—this provides some indication of the effectiveness of chest compressions and is helpful in detecting when ROSC has been achieved.

  • The presence of a CVC is helpful— drug delivery by this route is both rapid and reliable.

Postcardiac arrest management

The postresuscitation phase starts at the location where ROSC is achieved but, once stabilized, the patient is transferred to the most appropriate high-care area (e.g. emergency room, cardiac catheterization laboratory, or ICU) for continued diagnosis, monitoring, and treatment. The postresuscitation care algorithm (Figure 17.1) outlines some of the key interventions required to optimize outcome for these patients. Of those comatose patients admitted to ICUs after cardiac arrest, as many as 40–50% survive to be discharged from hospital depending on the cause of arrest, system, and quality of care. Of the patients who survive to hospital discharge, the vast majority have a good neurological outcome although many have subtle cognitive impairment.

Figure 17.1 Post-resuscitation care algorithm. CO/CI, Cardiac output/cardiac index; CT, computed tomography; CTPA, CT pulmonary angiogram; EEG, electroencephalography; ICD, implantable cardioverter defibrillator; MAP, mean arterial pressure; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; scvO2, central venous oxygen saturation; SpO2, peripheral capillary oxygen saturation.

Figure 17.1 Post-resuscitation care algorithm. CO/CI, Cardiac output/cardiac index; CT, computed tomography; CTPA, CT pulmonary angiogram; EEG, electroencephalography; ICD, implantable cardioverter defibrillator; MAP, mean arterial pressure; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; scvO2, central venous oxygen saturation; SpO2, peripheral capillary oxygen saturation.

Reproduced with the kind permission of the Resuscitation Council (UK).

The postcardiac arrest syndrome

The postcardiac arrest syndrome comprises:

  • Postcardiac arrest brain injury.

  • Postcardiac arrest myocardial dysfunction.

  • Systemic ischaemia/reperfusion response.

  • Persistent precipitating pathology.

  • Among patients surviving to ICU admission but subsequently dying in hospital, brain injury is the cause of death in approximately two-thirds after OHCA and approximately 25% after in-hospital cardiac arrest. Cardiovascular failure accounts for most deaths in the first 3 days, while brain injury accounts for most of the later deaths.

  • Postcardiac arrest brain injury may be exacerbated by microcirculatory failure, impaired autoregulation, hypotension, hypercarbia, hypoxaemia, hyperoxaemia, pyrexia, hypoglycaemia, hyperglycaemia, and seizures.

  • Significant myocardial dysfunction is common after cardiac arrest but typically starts to recover by 2–3 days, although full recovery may take significantly longer.

  • The whole body ischaemia/reperfusion of cardiac arrest activates immune and coagulation pathways, contributing to multiple organ failure and increasing the risk of infection. Thus, the postcardiac arrest syndrome has many features in common with sepsis, including intravascular volume depletion, vasodilation, endothelial injury, and abnormalities of the microcirculation.

Airway and ventilation

  • Hypoxaemia and hypercarbia both increase the likelihood of a further cardiac arrest and may contribute to secondary brain injury.

  • Several animal studies indicate that hyperoxaemia early after ROSC causes oxidative stress and harms postischaemic neurones. Analyses of intensive care registries have produced conflicting results: only some have shown an association between hyperoxaemia and poor outcome.

  • A recent study of air versus supplemental oxygen in ST-elevation myocardial infarction showed that supplemental oxygen therapy increased myocardial injury, recurrent myocardial infarction and major cardiac arrhythmia, and was associated with larger infarct size at 6 months.

  • As soon as arterial blood oxygen saturation can be monitored reliably (by blood gas analysis and/or pulse oximetry), titrate the inspired oxygen concentration to maintain the arterial blood oxygen saturation in the range of 94–98%.

  • After cardiac arrest, hypocapnia induced by hyperventilation causes cerebral ischaemia. Observational studies using cardiac arrest registries document an association between hypocapnia and poor neurological outcome.

  • Adjust ventilation to achieve normocarbia. One observational study has shown an association between tidal volumes of < 8 ml/kg predicted body weight (PBW) and better neurocognitive outcomes in postcardiac arrest patients. Given that these patients also develop a marked inflammatory response, it seems rational to apply protective lung ventilation: tidal volume 6–8 ml/kg ideal body weight and positive end-expiratory pressure 4–8 cmH2O.


Coronary reperfusion

Acute coronary syndrome (ACS) is a frequent cause of OHCA: an acute coronary artery lesion can be found in about two-thirds of OHCA patients without an obvious non-cardiac aetiology.

Percutaneous coronary intervention following ROSC with ST-elevation

  • In patients with ST segment elevation (STE) or left bundle branch block on the post-ROSC ECG, more than 80% will have an acute coronary lesion.

  • Immediate angiography and percutaneous coronary intervention (PCI) when indicated should be performed in resuscitated OHCA patients whose initial ECG shows STE, even if they remain comatose and ventilated.

PCI following ROSC without STE

  • The sensitivity and specificity of the usual clinical data, ECG, and biomarkers to predict an acute coronary artery occlusion as the cause of OHCA are unclear; the absence of STE may also be associated with ACS in patients with ROSC following OHCA.

  • Discuss and consider emergent cardiac catheterization laboratory evaluation after ROSC in patients with the highest risk of a coronary cause for their cardiac arrest.

  • Factors such as patient age, duration of CPR, haemodynamic instability, presenting cardiac rhythm, neurological status upon hospital arrival, and perceived likelihood of cardiac aetiology can influence the decision to undertake the intervention in the acute phase or to delay it until later in the hospital stay.

Indications and timing of computed tomography scanning

  • Early identification of a respiratory or neurological cause can be achieved by performing a brain and chest computed tomography (CT) scan at hospital admission, before or after coronary angiography.

  • In the absence of signs or symptoms suggesting a neurological or respiratory cause (e.g. headache, seizures, or neurological deficits for neurological causes, shortness of breath, or documented hypoxaemia in patients suffering from a known and worsening respiratory disease) or if there is clinical or ECG evidence of myocardial ischaemia, undertake coronary angiography first, followed by CT scan in the absence of causative lesions.

Haemodynamic management

  • Postresuscitation myocardial dysfunction causes haemodynamic instability, which manifests as hypotension, low cardiac index, and arrhythmias.

  • Perform early echocardiography in all patients to detect and quantify the degree of myocardial dysfunction.

  • Postresuscitation myocardial dysfunction often requires inotropic support, at least transiently.

  • The systematic inflammatory response that occurs frequently in postcardiac arrest patients may cause vasoplegia and severe vasodilation. Thus, noradrenaline, with or without dobutamine, and fluid is usually the most effective treatment.

  • Treatment may be guided by blood pressure, heart rate, urine output, rate of plasma lactate clearance, and central venous oxygen saturation. Serial echocardiography may also be used, especially in haemodynamically unstable patients.

  • Some centres advocate use of an intra-aortic balloon pump in patients with cardiogenic shock.

  • Optimal targets for mean arterial pressure (MAP) and/or systolic arterial pressure remain unknown. In the absence of definitive data, target the mean arterial blood pressure to achieve an adequate urine output (1 ml/kg/h) and normal or decreasing plasma lactate values, taking into consideration the patient’s normal blood pressure, the cause of the arrest, and the severity of any myocardial dysfunction.

Implantable cardioverter defibrillators

Consider insertion of an implantable cardioverter defibrillator (ICD) in ischaemic patients with significant left ventricular dysfunction, who have been resuscitated from a ventricular arrhythmia that occurred later than 24–48 h after a primary coronary event. ICDs may also reduce mortality in cardiac arrest survivors at risk of sudden death from structural heart diseases or inherited cardiomyopathies.

Disability (optimizing neurological recovery)

Cerebral perfusion

  • Immediately after ROSC there is a short period of multifocal cerebral no-reflow followed by transient global cerebral hyperaemia lasting 15–30 min. This is followed by up to 24 h of cerebral hypoperfusion while the cerebral metabolic rate of oxygen gradually recovers.

  • After asphyxial cardiac arrest, brain oedema may occur transiently after ROSC but it is rarely associated with clinically relevant increases in intracranial pressure.

  • Autoregulation of cerebral bloodflow is often impaired (absent or right-shifted) for some time after cardiac arrest; thus, after ROSC, maintain MAP near the patient’s normal level.


  • Although it has been common practice to sedate and ventilate patients for at least 24 h after ROSC, there are no high-level data to support a defined period of ventilation, sedation, and neuromuscular blockade after cardiac arrest.

  • Patients need to be sedated adequately during treatment with targeted temperature management (TTM), and the duration of sedation and ventilation is therefore influenced by this treatment.

  • Short-acting drugs (e.g. propofol, remifentanil) will enable more reliable and earlier neurological assessment and prognostication (see section on ‘Prognostication’).

Control of seizures

  • Seizures occur in approximately one-third of patients who remain comatose after ROSC.

  • Myoclonus is most common and occurs in 18–25%, the remainder having focal or generalized tonic-clonic seizures or a combination of seizure types. Clinical seizures, including myoclonus, may or may not be of epileptic origin. Other motor manifestations could be mistaken for seizures and there are several types of myoclonus, the majority being non-epileptic.

  • Use intermittent electroencephalography (EEG) to detect epileptic activity in patients with clinical seizure manifestations. Consider continuous EEG to monitor patients with a diagnosed status epilepticus and effects of treatment.

  • In comatose cardiac arrest patients, postanoxic status epilepticus was detected in 23–31% of patients using continuous EEG monitoring. Patients with electrographic status epilepticus may or may not have clinically detectable seizure manifestations that may be masked by sedation.

  • Seizures may increase the cerebral metabolic rate and have the potential to exacerbate brain injury caused by cardiac arrest: treat with sodium valproate, levetiracetam, phenytoin, benzodiazepines, propofol, or a barbiturate. Myoclonus can be particularly difficult to treat; phenytoin is often ineffective. Propofol is effective to suppress postanoxic myoclonus. Clonazepam, sodium valproate, and levetiracetam are antimyoclonic drugs that may be effective in postanoxic myoclonus.

  • Routine seizure prophylaxis in postcardiac arrest patients is not recommended because of the risk of adverse effects and the poor response to antiepileptic drugs among patients with clinical and electrographic seizures.

  • Myoclonus and electrographic seizure activity, including status epilepticus, are related to a poor prognosis, but individual patients may survive with good outcome.

Glucose control

  • There is a strong association between high blood glucose after resuscitation from cardiac arrest and poor neurological outcome.

  • Compared with normothermia, mild induced hypothermia is associated with higher blood glucose values, increased blood glucose variability, and greater insulin requirements. Increased blood glucose variability is associated with increased mortality and unfavourable neurological outcome after cardiac arrest.

  • Based on the available data, following ROSC, maintain the blood glucose at ≤10 mmol/l and avoid hypoglycaemia.

Temperature control

Treatment of hyperpyrexia

  • A period of hyperthermia (hyperpyrexia) is common in the first 48 h after cardiac arrest and is associated with worse outcome but there is no robust documenting causality.

  • Although the effect of elevated temperature on outcome is not proven, it seems reasonable to treat hyperthermia occurring after cardiac arrest with antipyretics and to consider active cooling in unconscious patients.


  • Animal and human data indicate that mild induced hypothermia is neuroprotective and improves outcome after a period of global cerebral hypoxia-ischaemia. Cooling suppresses many of the pathways leading to delayed cell death, including apoptosis (programmed cell death). Hypothermia decreases the cerebral metabolic rate for oxygen (CMRO2) by about 6% for each 1°C reduction in core temperature and this may reduce the release of excitatory amino acids and free radicals.

  • One randomized trial and a pseudorandomized trial demonstrated improved neurological outcome at hospital discharge or at 6 months in comatose patients who were cooled after out-of-hospital VF cardiac arrest. Cooling was initiated within minutes to hours after ROSC, and a temperature range of 32–34°C was maintained for 12–24 h.

  • In the TTM trial, there was no difference in mortality and detailed neurological outcome at 6 months among patients who were randomized to 36 h of temperature control (comprising 28 h at the target temperature followed by slow rewarm) at either 33°C or 36°C.

  • The optimal duration for mild induced hypothermia and TTM is unknown, although it is currently most commonly used for 24 h.

  • The term TTM or temperature control is now preferred over the previous term therapeutic hypothermia. The Advanced Life Support Task Force of the International Liaison Committee on Resuscitation made several treatment recommendations on TTM:

    • Maintain a constant, target temperature between 32°C and 36°C for those patients in whom temperature control is used.

    • TTM is recommended for adults after OHCA with an initial shockable rhythm who remain unresponsive after ROSC.

    • TTM is suggested for adults after OHCA with an initial non-shockable rhythm who remain unresponsive after ROSC.

    • TTM is suggested for adults after in-hospital cardiac arrest with any initial rhythm who remain unresponsive after ROSC.

    • If TTM is used, it is suggested that the duration is at least 24 h.

      The adoption of 36°C as the target temperature has several advantages compared with 33°C:

  • There is a reduced need for vasopressor support.

  • Lactate values are lower (the clinical significance of this is unclear).

  • The rewarming phase is shorter.

  • There is reduced risk of rebound hyperthermia after rewarming.

How to control temperature

The practical application of TTM, along with the physiological effects and complications of mild hypothermia, is described in detail in the section on ‘Targeted temperature management’ in Chapter 2.


  • Most deaths among comatose postcardiac arrest patients admitted to ICU are due to active withdrawal of life-sustaining treatment based on prognostication of a poor neurological outcome. Ideally, tests used for predicting a poor outcome should have 100% specificity or zero false positive rate (FPR), i.e. no individuals should have a ‘good’ long-term outcome if predicted to have a poor outcome.

  • Many prognostication studies are confounded by self-fulfilling prophecy, which is a bias occurring when the treating physicians are not blinded to the results of the outcome predictor and use it to make a decision on withdrawal of life-sustaining treatment.

  • Prognostication of the comatose postcardiac arrest patient should be multimodal and should be delayed sufficiently to enable full clearance of sedatives and any neurological recovery to occur—in most cases, prognostication is not reliable until after 72 h from cardiac arrest (Figure 17.2). The tests are categorized:

    • Cinical examination—Glasgow Coma Score, pupillary response to light, corneal reflex, presence of seizures.

    • Neurophysiological studies—somatosensory evoked potentials (SSEPs) and EEG.

    • Biochemical markers—neurone-specific enolase (NSE) is the most commonly used.

    • Imaging studies—brain CT and magnetic resonance imaging (MRI).

Figure 17.2 Prognostication strategy algorithm. NSE, Neurone-specific enolase.

Figure 17.2 Prognostication strategy algorithm. NSE, Neurone-specific enolase.

Reproduced with the kind permission of the Resuscitation Council (UK).

Clinical examination

  • Bilateral absence of pupillary light reflex at 72 h from ROSC predicts poor outcome with close to 0% FPR but the sensitivity is relatively low (about 19%); similar performance has been documented for bilaterally absent corneal reflex.

  • An absent or extensor motor response to pain at 72 h from ROSC has a high (about 75%) sensitivity for prediction of poor outcome, but the FPR is also high (about 27%). The high sensitivity of this sign enables it to be used to identify the population with poor neurological status needing prognostication.

  • The corneal reflex and the motor response can be suppressed by sedatives or neuromuscular blocking drugs. When interference from residual sedation or paralysis is suspected, prolong observation of these clinical signs beyond 72 h from ROSC so that the risk of obtaining FPRs is minimized.

  • While the presence of myoclonic jerks in comatose survivors of cardiac arrest is not consistently associated with poor outcome (FPR 9%), a status myoclonus starting within 48 h from ROSC is consistently associated with a poor outcome (FPR 0%; sensitivity 8–16%). However, several case reports of good neurological recovery despite an early-onset, prolonged, and generalized myoclonus have been published. In some of these cases myoclonus persisted after awakening and evolved into a chronic action myoclonus—the Lance-Adams syndrome).


  • In postarrest comatose patients, bilateral absence of the N20 short-latency SSEP wave predicts death or vegetative state (CPC 4–5) with high reliability (FPR 0–2% with upper 95% confidence interval [CI] of about 4%).

  • Background reactivity means that there is a change in the EEG in response to a loud noise or a noxious stimulus such as tracheal suction. Absence of EEG background reactivity predicts poor outcome, with a FPR of 0–2% (upper 95% CI of about 7%).

  • In TTM-treated patients, the presence of status epilepticus, i.e. a prolonged epileptiform activity, is almost invariably—but not always—followed by poor outcome (FPR 0–6%), especially in presence of an unreactive or discontinuous EEG background.

  • Burst-suppression has recently been defined as more than 50% of the EEG record consisting of periods of EEG voltage <10 µV, with alternating bursts. However, most prognostication studies do not comply with this definition. In comatose survivors of cardiac arrest, burst-suppression is usually a transient finding. During the first 24–48 h after ROSC, burst-suppression may be compatible with neurological recovery, while at ≥72 h from ROSC a persisting burst-suppression pattern is consistently associated with poor outcome.


  • NSE and S-100B are protein biomarkers that are released following injury to neurones and glial cells, respectively. Their blood values after cardiac arrest are likely to correlate with the extent of anoxic-ischaemic neurological injury and, therefore, with the severity of neurological outcome. NSE has been studied far more extensively than S-100 for prognostication after cardiac arrest.

  • In TTM-treated patients the threshold NSE values for 0% FPR varied between studies, but were as high as 150 µg/l at 24 and 48 h, and up to 80 µg/l at 72 h. Limited evidence suggests that the discriminative value of NSE levels at 48–72 h is higher than at 24 h. Increasing NSE values over time may have an additional value in predicting poor outcome.


  • The main CT finding of global anoxic-ischaemic cerebral insult following cardiac arrest is cerebral oedema, which appears as a reduction in the depth of cerebral sulci (sulcal effacement) and an attenuation of the grey matter/white matter interface.

  • Brain MRI is more sensitive than CT for detecting global anoxic-ischaemic brain injury due to cardiac arrest; however, its use can be problematic in the most clinically unstable patients. MRI can reveal extensive changes when results of other predictors such as SSEP are normal.

Suggested prognostication strategy

  • The process of brain recovery following global postanoxic injury is completed within 72 h from arrest in most patients. However, in patients who have received sedatives ≤12 h before the 72 h post-ROSC neurological assessment, the reliability of clinical examination may be reduced.

  • The prognostication strategy algorithm (Figure 17.2) is applicable to all patients who remain comatose with an absent or extensor motor response to pain at ≥72 h from ROSC. Results of earlier prognostic tests are also considered at this time point.


  • Although neurological outcome is considered to be good for the majority of cardiac arrest survivors, cognitive and emotional problems and fatigue are common.

  • Long-term cognitive impairments are present in half of survivors. Memory is most frequently affected, followed by problems in attention and executive functioning (planning and organization).

  • There is some evidence that follow-up care and rehabilitation after hospital discharge can improve outcome after cardiac arrest.

Cardiac arrest centres

  • Many studies have reported an association between survival to hospital discharge and transport to a cardiac arrest centre, but there is inconsistency in the hospital factors that are most related to patient outcome.

  • Most experts agree that such a centre must have a cardiac catheterization laboratory that is immediately accessible 24/7 and the facility to provide TTM.

  • The availability of a neurology service that can provide neuroelectrophysiological monitoring is essential.

  • There is indirect evidence that regional cardiac resuscitation systems of care improve outcome after ST-elevation myocardial infarction.

Fluid challenge


A fluid challenge is a specific volume of fluid given over a specified time period to determine whether the cardiac output will respond to further volume. It is one of the most common interventions in the ICU, but is open to wide interpretation.


Hypovolaemia may be due to bleeding, gastrointestinal, urinary, or skin losses, or may be caused by internal losses such as third spacing. In this situation there is a reduction in the body’s total fluid volume or an absolute hypovolaemia. Relative hypovolaemia, which is a lot more difficult to rationalize, may result from an increase in venous capacitance secondary to inflammatory processes such as sepsis or pancreatitis, or as a side-effect from drugs. Venous return and therefore preload is reduced, leading to a reduced stroke volume and cardiac output. Perfusion to vital organs is lowered and will lead to progressive organ failure if not corrected. Previously it was thought that circulatory support with inotropes was inappropriate in the hypovolaemic patient as it may increase myocardial oxygen demand. This may be true for absolute hypovolaemia, but not necessarily for relative hypovolaemia. There is currently little data to back this statement up and it will be difficult to prove clinically.

Overt hypovolaemia due to exsanguination is self-evident. However, it can be a difficult diagnosis in the critically ill patient as the clinical signs lack sensitivity and specificity. When resuscitating patients with upper gastrointestinal bleeding, it is worth considering data that suggest a target haemoglobin of 70 g/l may be better than 100 g/l, even in cases of absolute hypovolaemia.

The problem with a fluid bolus therapy

There are well-documented physiological effects of a fluid bolus, which Frank Starling first described. There have, until recently, been few data on clinical outcome in patients suffering with a pathological condition and what the effects of excess fluid might be on their long-term outcome. In addition, getting back to the physiological effects, most of our measurements are pressure- or perfusion-related. Measurement of intravascular volume remains elusive currently. So when the tone of the vascular tree changes there are large changes in both pressure and where the blood volume gets distributed, which in turns alters the clinical signs we might see. Whatever the background, though, fluid bolus therapy (FBT) is an established standard of care in the management of septic, hypotensive, tachycardic, and/or oliguric patients. Bellomo found 33 studies between 2010 and 2013 describing 41 boluses. No randomized trials compared FBT with alternative interventions such as vasopressors. Median fluid boluses were 500 ml over 30 min, with sodium chloride being the most commonly used fluid. No studies related the physiological changes after FBT with clinically relevant outcomes. Boulain described prospective practices of volume expansion in 19 French ICUs in February 2015. High between-centre variability characterized all the aspects of FBT prescription and monitoring, but overall haemodynamic exploration to help guide and monitor FBT was infrequent. This suggests that practice is not an exact science currently nor standardized!

Clinical indicators of hypovolaemia

  • Thirst, dry mouth, reduced skin turgor.

  • Tachycardia, reduced blood pressure, reduced central venous pressure (CVP)/pulmonary artery wedge pressure (PAWP).

  • Reduced urine output (<0.5 ml/kg/h), increased toe–core gap.

  • Raised urea, raised sodium, raised lactate, reduced urinary sodium (<20 mmol/l).

  • The use of echocardiography to assess cardiac filling is now commonplace on the ICU, along with ventricular volume, contractility, and IVC filling.

  • Variations in arterial pulse pressure with breathing in sedated mechanically ventilated patients are due to changes in stroke volume that occur with changes in intrathoracic pressure and may suggest hypovolaemia.

  • Passive leg raising to increase venous return temporarily can be used but may not be reliable in awake patients, especially if they get pain on movement.

While abnormal values suggest hypovolaemia, normal values do not exclude it.

Unfortunately there is no linear relationship between pressure and volume in a vascular compartment that can change its capacitance threefold. Therefore, the response to fluid is not reliably predictable for any given CVP and may even fall with volume repletion (e.g. in conditions with intense peripheral vasoconstriction such as pre-eclampsia). The CVP may be falsely high if the patient has intrinsic heart or lung disease.

A more dynamic measurement of the likely response to fluid can be obtained by administering a specific volume of fluid as a fluid challenge. For the fluid challenge to result in an increase in stroke volume and cardiac output, it has to increase cardiac preload significantly and this has to increase stroke volume significantly. Therefore, the patient can be a non-responder because either preload is not increased or one or both of the ventricles is operating on the flat part of the Frank–Starling curve.

Performing a fluid challenge

To test this mechanism requires a variable amount of fluid. Filling pressures represent the net effect of preload, ventricular compliance, and afterload. The initial fluid challenge technique proposed by Weil and Henning in 1979 measured CVP at 10-min intervals after 100–200 ml of fluid. If the change in CVP was <2 mmHg, the fluid was continued. If it was 2–5 mmHg it was stopped and the CVP remeasured after 10 min. If it was >5 mmHg, it was stopped. The values were 3–7 mmHg if the PAWP was being used.

Vincent later modified this technique, allowing for the continuous monitoring that became available. He suggested a larger volume over a longer time period in line with the regime suggested in the surviving sepsis campaign (i.e. 500–1000 ml crystalloid or 300–500 ml colloid over 30 min). Goals should be set at the outset, such as an increase in MAP. Because the most serious adverse effect of a fluid challenge is acute pulmonary oedema secondary to congestive cardiac failure, Vincent suggested setting ‘safety limits’ such as a set CVP/PAWP which, when reached, alerts the practitioner to stop the infusion. If the MAP is rising along with the CVP, fluid can be infused until the desired MAP is reached. If the CVP is rising without any change in MAP, this indicates the fluid challenge is unsuccessful and other forms of circulatory support are required.

Currently there are many parameters used, from clinical assessment to direct measurement using devices. However, it has been shown by Boulain and in the FENICE study that there is often no rational for giving a fluid bolus in most cases. The surviving sepsis campaign from 2012 talks about mainly the use of crystalloid and mentions terms like ‘adequate fluid resuscitation’. It suggests caution if a patient has had >30 ml/kg of boluses and if they are more than 20 ml/kg positive in a 24-hour period.

Type of fluid

The European Society of Intensive Care produced a consensus statement in 2012, which stated ‘We recommend not to use HES [hydroxyethyl starches] with molecular weight C200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established.’ Prior to this there was wide use of many different fluids.

Detailed review of both colloids and crystalloid fluids can be found in Chapter 10.

The future

Better answers in terms of clinical outcomes should be available in the future, which will inform us about which crystalloid is best and what amount of fluid to give to a shocked patient.

Multiple choice questions and further reading

Resuscitation Interactive multiple choice questions to test your knowledge on this chapter and additional further reading can be found in Appendix Chapter 17 Multiple choice questions and further reading