Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication: A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke (Part II)☆,☆☆,⋆
Section snippets
Therapeutic hypothermia
Therapeutic hypothermia should be part of a standardised treatment strategy for comatose survivors of cardiac arrest (Sunde et al., 2007, Nolan et al., 2003, Soar and Nolan, 2007). Two randomized clinical trials and a meta-analysis showed improved outcome in adults who remained comatose after initial resuscitation from out-of-hospital ventricular fibrillation (VF) cardiac arrest and who were cooled within minutes to hours after ROSC (HCAG, 2002, Bernard et al., 2002, Holzer et al., 2005).
Sedation and neuromuscular blockade
If patients do not show adequate signs of awakening within the first 5–10 min after ROSC, tracheal intubation (if not already achieved), mechanical ventilation, and sedation will be required. Adequate sedation will reduce oxygen consumption, which is further reduced with therapeutic hypothermia. Use of published sedation scales for monitoring these patients (e.g., the Richmond or Ramsay Scales) may be helpful (Ely et al., 2003, De Jonghe et al., 2000). Both opioids (analgesia) and hypnotics
Seizure sincre and prevention
Seizures or myoclonus or both occur in 5–15% of adult patients who achieve ROSC and 10–40% of those who remain comatose (Krumholz et al., 1988, Levy et al., 1985, Snyder et al., 1980, Zandbergen et al., 2006a). Seizures increase cerebral metabolism by up to 3-fold (Ingvar, 1986). No studies directly address the use of prophylactic anticonvulsant drugs after cardiac arrest in adults. Anticonvulsants such as thiopental, and especially phenytoin, are neuroprotective in animal models (Ebmeyer et
Glucose control
Tight control of blood glucose (4.4–6.1 mmol L−1 or 80–110 mg dL−1) with insulin reduced hospital mortality rates in critically ill adults in a surgical ICU (van den Berghe et al., 2001) and appeared to protect the central and peripheral nervous system (Van den Berghe et al., 2005). When the same group repeated this study in a medical ICU, the overall mortality rate was similar in the intensive insulin and control groups (Van den Berghe et al., 2006). Among the patients with an ICU stay of >3 days,
Neuroprotective pharmacology
Over the past 3 decades investigators have used animal models of global cerebral ischaemia to study numerous neuroprotective modalities, including anesthetics, anticonvulsants, calcium and sodium channel antagonists, N-methyl D-aspartate (NMDA)-receptor antagonists, immunosuppressants, growth factors, protease inhibitors, magnesium, and 7-aminobutyric acid (GABA) agonists. Many of these targeted pharmacological neuroprotective strategies that focus on specific injury mechanisms have shown
Adrenal dysfunction
Relative adrenal insufficiency occurs frequently after successful resuscitation of out-of-hospital cardiac arrest and is associated with increased mortality (see Section ‘Epidemiology of the post-cardiac arrest syndrome’) (Hekimian et al., 2004, Pene et al., 2005). One small study has demonstrated increased ROSC when patients with out-of-hospital cardiac arrest were treated with hydrocortisone (Tsai et al., 2007), but the use of steroids has not been studied in the post-cardiac arrest phase.
Renal failure
Renal failure is common in any cohort of critically ill patients. In a recent study of comatose survivors of out-of-hospital cardiac arrest, 5 of 72 (7%) received haemodialysis, and the incidence was the same with or without the use of therapeutic hypothermia (Knafelj et al., 2007). In another study, renal function was impaired transiently in out-of-hospital post-cardiac arrest patients treated with therapeutic hypothermia, required no interventions, and returned to normal by 28 days (Zeiner et
Infection
Complications inevitably occur during the treatment of post-cardiac arrest patients as they do during the treatment of any critically ill patients. Although several studies have shown no statistical difference in complication rates between patients with out-of-hospital cardiac arrest who are treated with hypothermia and those who remain normothermic, these studies are generally underpowered to show this conclusively (Oddo et al., 2006, Busch et al., 2006). Pneumonia caused by aspiration or
Placement of implantable cardioverter-defibrillators
In survivors with good neurological recovery, insertion of an ICD is indicated if subsequent cardiac arrests cannot be reliably prevented by other treatments (such as a pacemaker for atrioventricular block, transcatheter ablation of a single ectopic pathway, or valve replacement for critical aortic stenosis) (AVID, 1997, Connolly et al., 2000a, Connolly et al., 2000b, Kuck et al., 2000, Moss et al., 2002, Zipes et al., 2006, Bardy et al., 2005, Ezekowitz et al., 2003, Goldberger and Lampert,
Long-term management
Issues related to long-term management are beyond the scope of this scientific statement but include cardiac and neurological rehabilitation and psychiatric disorders.
Post-cardiac arrest prognostication
With the brain’s heightened susceptibility to global ischaemia, the majority of cardiac arrest patients who are successfully resuscitated have impaired consciousness, and some remain in a vegetative state. The need for protracted high-intensity care of neurologically devastated survivors presents an immense burden to healthcare systems, patients’ families, and society in general (Gray et al., 1991, Hamel et al., 2002). To limit this burden, clinical factors and diagnostic tests are used to
Pre-cardiac arrest factors
Many studies have identified factors associated with poor functional outcome after resuscitation, but no studies have shown a reliable predictor of outcome. Advanced age is associated with decreased survival after resuscitation (Sandroni et al., 2007, Skogvoll et al., 1999, Skrifvars et al., 2007), but at least one study suggested that advanced age did not predict poor neurological outcome in survivors (Rogove et al., 1995). Race (Chu et al., 1998, Ebell et al., 1995, Becker et al., 1993) and
Intra-cardiac arrest factors
Many factors during the resuscitation process have been associated with functional outcome, but no single factor has been identified as a reliable predictor. Some association with poor functional outcome has been made between a long interval between collapse and the start of CPR and increased duration of CPR to ROSC (Rogove et al., 1995, Berek et al., 1997), but high false-positive rates make these unreliable for predicting poor outcome (Wijdicks et al., 2006). Furthermore, the quality of CPR
Post-cardiac arrest factors
The bedside neurological examination remains one of the most reliable and widely validated predictors of functional outcome after cardiac arrest (Levy et al., 1985, Wijdicks et al., 2006, Booth et al., 2004, Zandbergen et al., 1998). With sudden interruption of blood flow to the brain, higher cortical functions, such as consciousness, are lost first, whereas lower brain-stem functions, such as spontaneous breathing activity, are lost last (Jorgensen, 1997). Not surprisingly, retention of any
Neurophysiological tests
The recording of somatosensory-evoked potentials (SSEP) is a neurophysiological test of the integrity of the neuronal pathways from a peripheral nerve, spinal cord, or brainstem to the cerebral cortex (Young, 2000, Rothstein, 2000). The SSEP is probably the best and most reliable prognostic test because it is influenced less by common drugs and metabolic derangements. The N20 component (representing the primary cortical response) of the SSEP with median nerve stimulation is the best studied
Neuroimaging and monitoring modalities
Neuroimaging is performed to define structural brain injury related to cardiac arrest. The absence of a well-designed study has limited the use of neuroimaging in the prediction of outcome after cardiac arrest. The most common type of neuroimaging studied has been cranial CT. Cranial CT studies can show widespread injury to the brain with changes in oedema characteristics (Torbey et al., 2000, Torbey et al., 2004). Acquiring MRI studies is challenging in critically ill patients because of
Biochemical markers
Biochemical markers derived initially from cerebrospinal fluid (CSF) (creatine phosphokinase [CPK]-BB) (Tirschwell et al., 1997, Longstreth et al., 1981) or peripheral blood (neuron-specific enolase [NSE] and S100β) have been used to prognosticate functional outcome after cardiac arrest. The ease of obtaining samples has favored blood-based biochemical markers over those in CSF. NSE is a cytoplasmic glycolytic enzyme found in neurons, cells, and tumors of neuroendocrine origin; concentrations
Multimodality prediction of neurological outcome
More accurate prognostication can potentially be achieved by using several methods to investigate neurological injury. Some studies have suggested that combining neurological examination with other adjunctive tests enhances the overall accuracy and efficiency of prognosticating poor outcome (Booth et al., 2004, Bassetti et al., 1996, Madl et al., 2000, Zandbergen et al., 2006c). No clinical decision rule or multimodal prognostication protocol has been prospectively validated, however.
Prognostication in hypothermia-treated patients
Therapeutic hypothermia improved survival and functional outcome for one in every 6 comatose cardiac arrest survivors treated (Holzer et al., 2005). As a neuroprotective intervention, hypothermia alters the progression of neurological injury; hypothermia alters the evolution of recovery when patients who received therapeutic hypothermia are compared with those who did not. Therefore, prognostication strategies established in patients who were not treated with hypothermia might not accurately
Paediatrics: special considerations
In children, cardiac arrests are caused typically by respiratory failure, circulatory shock or both. In contrast to adults, children rarely develop sudden arrhythmogenic VF arrests from coronary artery disease. Arrhythmogenic VF/ventricular tachycardia (VT) arrests occur in 5–20% of out-of-hospital paediatric cardiac arrests and approximately 10% of in-hospital paediatric arrests (Nadkarni et al., 2006, Young et al., 2004, Samson et al., 2006, Herlitz et al., 2005, Tibballs and Kinney, 2006).
Temperature management
Mild hypothermia is a promising neuroprotective and cardio-protective treatment in the postarrest phase (Nolan et al., 2003, Holzer et al., 2005, Bernard and Buist, 2003) and is a well-established treatment in adult survivors of cardiac arrest (Oddo et al., 2006, Sunde et al., 2007). Studies of hypoxic-ischaemic encephalopathy in newborns indicate that mild hypothermia is safe and feasible and may be neuroprotective (Azzopardi et al., 2000, Gluckman et al., 2005, Wyatt et al., 2007, Gunn et
Extracorporeal membrane oxygenation
Perhaps the ultimate technology to control postresuscitation temperature and haemodynamic parameters is ECMO. Several studies have shown that placing children on ECMO during prolonged CPR (E-CPR) can result in good outcomes. In one report, 66 children were placed on ECMO during CPR over 7 years (Morris et al., 2004). The median duration of CPR before establishment of ECMO was 50 min, and 35% (23 of 66) of these children survived to hospital discharge. These children had only brief periods of no
Paediatric cardiac arrest carerequires
High-quality multimodal postarrest care improves survival and neurological outcome in adults (Sunde et al., 2007).
Paediatric post-cardiac arrest care requires specifically adapted equipment and training to deliver critical interventions rapidly and safely to avoid latent errors and preventable morbidity and mortality. Survival of children after in-hospital arrest is greater when they are treated in hospitals that employ specialized paediatric staff (Donoghue et al., 2006). These data suggest
Challenges to implementation
Publication of clinical guidelines alone is frequently inadequate to change practice. There are often several barriers to changing clinical practice, and these will need to be identified and overcome before changes can be implemented. The purpose of the following section is to provide insight into the challenges and barriers to implementing optimized post-cardiac arrest care.
Existing studies showing poor implementation
In 2003 the advanced life support task force of the International Liaison Committee on Resuscitation (ILCOR) published an advisory statement on the use of therapeutic hypothermia (Nolan et al., 2003). This statement recommended that comatose survivors of out-of-hospital VF cardiac arrest should be cooled to 32–34 °C for 12–24 h. Despite this recommendation, which was based on the results of 2 randomized controlled trials, implementation of therapeutic hypothermia has been slow. A survey of all
Barriers to implementation
The numerous barriers to implementation of guidelines have been recently described and may be classified as structural, personal, or environmental (Table 1) (Bosse et al., 2006).
Implementation strategies
Clinical guidelines that are evidence-based and strongly supported by well recognised and respected professional organizations are more likely to be adopted by practicing clinicians. Many strategies to improve implementation have been described (Table 2) (Bosse et al., 2006, Grol and Grimshaw, 2003).
Monitoring of implementation
All clinical practices should be audited, especially when change is implemented. By measuring current performance against defined standards (e.g., time to achieve target temperature when using therapeutic hypothermia), it is possible to identify which local protocols and practices need modification. Process as well as clinical factors should be monitored as part of the quality program. The iterative process of reaudit and further change as necessary should enable optimal performance. Ideally
Resource issues
Many of the interventions applied in the postresuscitation period do not require expensive equipment. The more expensive cooling systems have some advantages but are by no means essential. Maintenance of an adequate mean arterial blood pressure and control of blood glucose are also relatively inexpensive interventions. In some healthcare systems the lack of 24 h interventional cardiology systems makes it difficult to implement timely PCI, but in most cases it should still be possible to achieve
Practical problems
Postresuscitation care is delivered by many different groups of healthcare providers in multiple locations. Pre-hospital treatment by EMS may involve both paramedics and physicians, and continuation of treatment in-hospital will involve emergency physicians and nurses, cardiologists, neurologists, critical care physicians and nurses, and cardiac catheter laboratory staff. Treatment guidelines will have to be disseminated across all these specialty groups. Implementation in all these
Critical knowledge gaps
In addition to summarizing what is known about the pathophysiology and management of post-cardiac arrest syndrome, a goal of this statement is to highlight what is not known. Table 3 outlines the critical knowledge gaps identified by the writing group. The purpose of this list is to stimulate preclinical and clinical research that will lead to evidence-based optimization of post-cardiac arrest care.
Acknowledgments
This paper was originally co-published in Resuscitation and Circulation. This article is republished with permission from Circulation. 2008; 118:2452–2483 © 2008, American Heart Association, Inc. and Resuscitation. 79/3:350–379 © 2008 Elsevier Ireland Ltd. With the permission of the authors the paper has been divided into two parts. The first part was published in issue 17/4. The reference section is published in full in both parts.
References (215)
- et al.
Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey
Resuscitation
(2005) - et al.
A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest
Resuscitation
(2004) - et al.
Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric ventricular fibrillation
Resuscitation
(2004) - et al.
Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric ventricular fibrillation
J. Am. Coll. Cardiol.
(2005) - et al.
Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest
Ann. Emerg. Med.
(1997) - et al.
Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report
Resuscitation
(2003) - et al.
The resistance to changing guidelines – what are the challenges and how to meet them
Best Pract. Res. Clin. Anaesthesiol.
(2006) - et al.
Prognostic significance of the difference between mixed venous and jugular bulb oxygen saturation in comatose patients resuscitated from a cardiac arrest
Resuscitation
(1999) - et al.
Myoclonus: current concepts and recent advances
Lancet Neurol.
(2004) - et al.
Race and survival after out-of-hospital cardiac arrest in a suburban community
Ann. Emerg. Med.
(1998)
Thiopental combination treatments for cerebral resuscitation after prolonged cardiac arrest in dogs. Exploratory outcome study
Resuscitation
Moderate hypothermia in neonatal encephalopathy: safety outcomes
Pediatr. Neurol.
Persistent hyperglycemia in critically ill children
J. Pediatr.
Biphasic concentration change during continuous midazolam administration in brain-injured patients undergoing therapeutic moderate hypothermia
Resuscitation
Scientific knowledge gaps and clinical research priorities for cardiopulmonary resuscitation and emergency cardiovascular care identified during the 2005 international consensus conference on ECC and CPR science with treatment recommendations. A consensus statement from the international liaison committee on resuscitation; the American heart association emergency cardiovascular care committee; the stroke council; and the cardiovascular nursing council
Resuscitation
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial
Lancet
Does the Mainz Emergency Evaluation Scoring (MEES) in combination with capnometry (MEESc) help in the prognosis of outcome from cardiopulmonary resuscitation in a prehospital setting?
Resuscitation
From best evidence to best practice: effective implementation of change in patients’ care
Lancet
Feasibility and efficacy of a new non-invasive surface cooling device in post-resuscitation intensive care medicine
Resuscitation
Characteristics and outcome among children suffering from out of hospital cardiac arrest in Sweden
Resuscitation
Brain injury from cardiac arrest in children
Neurol. Clin.
EEG should be performed during induced hypothermia
Resuscitation
Course of neurological recovery and cerebral prognostic signs during cardio-pulmonary resuscitation
Resuscitation
CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man
J. Neurol. Sci.
Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning
J. Am. Coll. Cardiol.
Defibrillation threshold and cardiac responses using an external biphasic defibrillator with pediatric and adult adhesive patches in pediatric-sized piglets
Resuscitation
Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest – a feasibility study
Resuscitation
Cold infusions alone are effective for induction of therapeutic hypothermia but do not keep patients cool after cardiac arrest
Resuscitation
Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction
Resuscitation
Impact of community-wide deployment of biphasic waveform automated external defibrillators on out-of-hospital cardiac arrest in Taipei
Resuscitation
Intra-arrest cooling improves outcomes in a murine cardiac arrest model
Circulation
Quality of cardiopulmonary resuscitation during in-hospital cardiac arrest
JAMA
End-tidal carbon dioxide measurements as a prognostic indicator of outcome in cardiac arrest
Am. J. Crit. Care
Clinical application of mild therapeutic hypothermia after cardiac arrest
Crit. Care Med.
Hypoxia and related conditions
Pilot study of treatment with whole body hypothermia for neonatal encephalopathy
Pediatrics
Predictors of survival following in-hospital cardiopulmonary resuscitation. A moving target
Arch. Intern. Med.
Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure
N. Engl. J. Med.
Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients
J. Neurol. Neurosurg. Psychiat.
Treatment of term infants with head cooling and mild systemic hypothermia (350 °C and 34.5 °C) after perinatal asphyxia
Pediatrics
Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago project
N. Engl. J. Med.
The prognostication of cerebral hypoxia after out-of-hospital cardiac arrest in adults
Eur. Neurol.
Induced hypothermia in critical care medicine: a review
Crit. Care Med.
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia
N. Engl. J. Med.
Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest
JAMA
Intensive insulin therapy and pentastarch resuscitation in severe sepsis
N. Engl. J. Med.
Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors
Acta Anaesthesiol. Scand.
Cited by (0)
- ☆
A Spanish translated version of the summary of this article appears as Appendix in the online version at doi:10.1016/j.resuscitation.2008.09.17.
- ☆☆
Endorsed by the American College of Emergency Physicians, Society for Academic Emergency Medicine, Society of Critical Care Medicine, and Neurocritical Care Society.
- ⋆
This article was originally co-published in Resuscitation and Circulation. This article is republished with permission from Circulation. 2008; 118:2452–2483 © 2008, American Heart Association, Inc. and Resuscitation. 79/3: 350–379 © 2008 Elsevier Ireland Ltd.