Syndrome post-arrêt cardiaque : aspects physiopathologiques,cliniques et thérapeutiques

Objective

This review aims at providing an update on post-cardiac arrest syndrome, from pathophysiology to treatment.

Data sources

Medline database.

Data extraction

All data on pathophysiology, clinical manifestations and therapeutic management, with focus on the publications of the 5 last years.

Data synthesis

Care of the patients after cardiac arrest is a medical challenge, in face of “post-cardiac arrest syndrome”, which culminates into multi-organ failure. This syndrome mimics sepsis-related dysfunctions, with all clinical and biological manifestations related to the phenomenon of global ischemia-reperfusion. Acute cardiocirculatory dysfunction is usually controlled through pharmacological and mechanical support. Meanwhile, as a majority of cardiac arrest is related to myocardial infarction, early angiographic exploration should then be discussed when there is no obvious extracardiac cause, percutaneous coronary revascularization being associated with improved short and long-term prognosis. Therapeutic hypothermia is the cornerstone of neuroprotective armamentarium, beyond hemodynamic stabilization and metabolic maintenance.

Conclusion

If ongoing evaluations should shed light on potential efficiency of new therapeutic drugs, a multidisciplinary approach of the post-cardiac arrest syndrome in expertise centre is essential.     

Cardiopulmonary resuscitation and post-resuscitation care

Survival following cardiac arrest depends on early recognition and effective treatment with high-quality chest compressions with minimal interruption, ventilation, treatment of reversible causes, and defibrillation if appropriate. Successfully resuscitated patients can develop a ‘SIRS-like’ post-cardiac arrest syndrome. Post-cardiac arrest care includes coronary reperfusion, control of oxygenation and ventilation, circulatory support, glucose control, treatment of seizures, and therapeutic hypothermia. Prognostication in comatose survivors is challenging. Approximately one-third of cardiac arrest survivors admitted to intensive care are discharged home.     

Therapiestrategien des Post-Reanimationssyndromes

Outcome after cardiopulmonary arrest is still poor. In cases of successful resuscitation post-cardiac arrest syndrome develops which is characterized by myocardial dysfunction, brain injury and unspecific inflammatory pathways. Therapeutic strategies focus on the maintenance of vital functions, causal treatment of the reason for cardiac arrest and the post-cardiac arrest syndrome. Continuous monitoring of hemodynamic (heart rate, rhythm, blood pressure, central venous pressure, diuresis), respiratory (oxygen saturation, p_aO₂, p_aCO₂) and metabolic (pH, lactate, blood glucose) parameters are necessary to detect trends. In recent years mild therapeutic hypothermia has influenced the prognosis of post-cardiac arrest patients in a significantly positive manner regarding mortality and quality of survival. Hypothermia should be started as soon as possible with a target temperature of 33°C (±1°C) for at least 24–48 h. To asses the neurological prognosis a clinical examination in combination with somatosensory evoked potentials seems to be most effective. Additionally, NSE and S100 provide further information with respect to the neurological outcome in the post-cardiac arrest period.     

Les dangers de l’hypothermie thérapeutique

Therapeutic hypothermia (less than 35 °C) is a promising strategy to improve neuroprotection after severe brain injury. Except in patients resuscitated from cardiac arrest, its effectiveness has not yet been demonstrated. Therapeutic hypothermia results in various side effects, including cardiovascular, hydroelectrolytic and infectious disorders, which could explain, in part, the lack of conclusive clinical studies. These hazards are associated with practical difficulties to induce and maintain targeted hypothermia and with rewarming management. An improvement in the techniques for achieving targeted hypothermia, more knowledge about side effects and further randomized clinical trials are needed before recommending the use of therapeutic hypothermia for patients with severe traumatic brain injury.     

Clinical neuroprotection and secondary neuronal injury mechanisms

Cerebral injury is a common cause of severe morbidity and mortality and is frequently encountered by anaesthetists and intensive care physicians in clinical practice. Insults may arise from a variety of medical and surgical conditions, including stroke, subarachnoid haemorrhage, central nervous system infection, epilepsy, post-cardiac arrest, and traumatic brain injury (TBI).Although the primary damage to brain tissue may be irreversible, aggressive early treatment may limit the ensuing secondary brain injury and reduce the risk of severe disability or death. Neuroprotection involves physiological, pharmacological and surgical interventions, initiated before the onset of ischaemia that can modify the cascade of events that lead to permanent cell damage when left unchecked.     

Delayed cardiac tamponade after blunt chest trauma: case report

A case of cardiac tamponade without evidence of hemopericardium within 2 weeks after blunt chest trauma is reported. The cause was a pericardial effusion that may have resulted from the post-cardiac injury syndrome. Pericardiotomy drained 600 mL of straw-colored clear fluid. A high index of suspicion for cardiac tamponade must be maintained in such patients for weeks after injury.     

Complications cardiovasculaires de l’agression cérébrale

The clinical importance of cardiovascular consequences resulting from cerebral injury has long been recognized. However, interactions between the brain and the cardiovascular system remain poorly defined and their importance for the management of patients suffering from acute brain injury is largely underestimated. This should have profound consequences on treatment strategies during anaesthesia and intensive cares of these patients, taking into account not only brain perfusion, but also cardiovascular optimisation. This report summarizes the main data available regarding the cardiovascular consequences of brain death, traumatic brain injury, stroke and epilepsy.     

Extracorporeal membrane oxygenation for pediatric cardiopulmonary failure

Extracorporeal membrane oxygenation is now standard treatment of severe respiratory failure in newborn infants in our center (200 cases) and worldwide (over 2500 cases), but there are few reports of such trials in older children. We reviewed our experience with extracorporeal membrane oxygenation in 33 children aged 1 week to 18 years between 1971 and 1989. The modality was used when all other treatment failed. Extracorporeal membrane oxygenation provided excellent cardiopulmonary support for 1 to 25 days (average 7 1/2 days). The survival rate was 25% for cardiac support patients and 47% for respiratory failure patients (36% overall survival). Mechanical complications included membrane lung failure, tubing rupture, and pump failure, all managed without mortality. Physiologic complications included bleeding, pneumothorax, cardiac arrest, renal failure, hepatic failure, and brain injury. The major cause of death was irreversible injury to lung, heart, or brain. Extracorporeal life support is a reasonable approach for children with serious but reversible cardiopulmonary failure.     

Commotio cordis après impact précordial de Flashball

Less lethal weapons, like Flashball^®, are more and more used since 1995 in law enforcement, even by the local police to neutralize combative individuals and to disperse riot crowds. This gun fires large rubber bullets and has been incriminated many times in cases of face injuries with functional consequences. In this case report, we mention a case of sudden death from cardiac arrest due to low energy chest wall impact of a rubber bullet shot with the Flashball. Commotio cordis is potentialized by a lethal set of three including, a certain impact velocity, an exact location of the hit over the cardiac silhouette, and a precise timing 15 m/s prior to the peak of the T-wave. This case report highlights the fact that such impacts can cause significant injury to internal organs, in particular circonstances, implying the necessity of a raising awareness of the medical staff, in ordre to not underestimate the severity of such injuries.     

Risk in pediatric anesthesia

Risk in pediatric anesthesia can be conveniently classified as minor or major. Major morbidity includes cardiac arrest, brain damage and death. Minor morbidity can be assessed by clinical audits with small patient samples. Major morbidity is rare. It is best assessed by very large clinical studies and by review of closed malpractice claims. Both minor and major morbidity occur most commonly in infants and children under three, especially those with severe co‐morbidities. Knowledge of risk profiles in pediatric anesthesia is a starting point for the reduction of risk.     

Prolonged somatic survival of clinically brain-dead adult patient

A 43-year-old woman suffered clinical brain death after severe head injury. The patient met the criteria for the diagnosis of clinical brain death on Day 3. Aggressive hemodynamic and respiratory managements coupled with triple hormone therapy were performed at the family's request, resulting in continued cardiac activity for a prolonged period. Spinal reflexes and automatisms were observed until cardiac arrest. Ventilatory support was discontinued on Day 168, when cardiac death was confirmed, and her kidneys and eyeballs were removed for transplantation. The patient survived for 165 days after the diagnosis of clinical brain death, which is an extremely prolonged period of somatic support for an adult patient after brain death. An extensive and informed discussion on the end-of-life treatment of clinically brain-dead patients is urgently required in Japan to establish treatment guidelines for such patients.     

Œdème cérébral : nouvelles pistes thérapeutiques

Cerebral oedema (CO) after brain injury can occur from different ways. The vasogenic and cytotoxic oedema are usually described but osmotic and hydrostatic CO, respectively secondary to plasmatic hypotonia or increase in blood pressure, can also be encountered. Addition of these several mechanisms can worsen injuries. Consequences are major, leading quickly to death secondary to intracerebral hypertension and later to neuropsychic sequelae. So therapeutic care to control this phenomenon is essential and osmotherapy is actually the only way. A better understanding of physiopathological disorders, particularly energetic ways (lactate), aquaporine function, inflammation lead to new therapeutic hopes. The promising experimental results need now to be confirmed by clinical data.     

Post–Cardiac Arrest Syndrome: Update on Brain Injury Management and Prognostication

Treatment of cardiac arrest should focus on maximizing neurologic recovery as well as systemic recovery to ensure the best possible functional outcome. This article focuses on the neurologic care of patients after they have been resuscitated from cardiac arrest. Maximizing neurologic outcome after cardiac arrest requires attention to prevention of primary and secondary brain injury. Primary brain injury such as hypoperfusion and hypoxic injury should be avoided by optimizing hemodynamic goals to maximize cerebral perfusion and maintain normoxia and normocarbia. Secondary brain injury mediated by excitotoxicity and the inflammatory cascade may be mitigated by therapeutic hypothermia. Other strategies that may be beneficial include the treatment of seizures and maintaining normoglycemia. Finally, accurate and timely prognostication is crucial because it influences withdrawal of care and overall mortality. With the adoption of therapeutic hypothermia, the classic prognostic paradigm that was previously used needs to be reexamined. The application of our knowledge of risk factors for poor outcome, serial physical examinations, neurophysiological tests, neuroimaging, and biochemical markers may need to be delayed until after rewarming. We emphasize the importance of a shift in physicians’ approach to the management of post–cardiac arrest syndrome, not only in prognostication, but also in the early and aggressive therapies that have been shown to improve survival and quality of life.     

Red Cell Distribution Width in Diagnosis of Brain Death

IntroductionRed blood cell distribution (RDW) is a hematologic index automatically calculated by blood cell counters. Research about RDW in traumatic brain injury showed positive correlation between high RDW values and mortality, which inspired us to investigate whether RDW could be used as a supportive diagnostic biomarker for diagnosis of brain death. Our hypothesis is that RDW may be useful as a biomarker that supports the diagnosis of brain death.MethodsAfter approval of the ethics committee, 209 patients who had been diagnosed with brain death between January 2012 and July 2018 were retrospectively reviewed. The RDW values of patients on the days of admission, brain death, and cardiac arrest were recorded. Data were collected from hospital database and patient charts.ResultsStatistical analysis revealed that the RDW values on the days of brain death and cardiac arrest were significantly higher than on the day of admission. In addition, the RDW values for the cardiac arrest day were significantly higher than on the day of brain death (P < .001).ConclusionsWe can say that the increase in RDW, which is reported to be an indicator of mortality for many diseases, can be a supporting biomarker for brain death diagnosis when evaluated concomitantly with clinical diagnostic criteria.     

A 10 min “no‐touch” time – is it enough in DCD? A DCD Animal Study

Donation after cardiac death (DCD) is under investigation because of the lack of human donor organs. Required times of cardiac arrest vary between 75s and 27min until the declaration of the patients' death worldwide. The aim of this study was to investigate brain death in pigs after different times of cardiac arrest with subsequent cardiopulmonary resuscitation (CPR) as a DCD paradigm. DCD was simulated in 20 pigs after direct electrical induction of ventricular fibrillation. The "no-touch" time varied from 2min up to 10min; then 30min of CPR were performed. Brain death was determined by established clinical and electrophysiological criteria. In all animals with cardiac arrest of at least 6min, a persistent loss of brainstem reflexes and no reappearance of bioelectric brain activity occurred. Reappearance of EEG activity was found until 4.5min of cardiac arrest and subsequent CPR. Brainstem reflexes were detectable until 5min of cardiac arrest and subsequent CPR. According to our experiments, the suggestion of 10min of cardiac arrest being equivalent to brain death exceeds the minimum time after which clinical and electrophysiological criteria of brain death are fulfilled. Therefore shorter "no-touch" times might be ethically acceptable to reduce warm ischemia time.     

Post-cardiac arrest syndrome after general anesthesia: role of therapeutic hypothermia and remifentanil

Moderate therapeutic hypothermia is often used in aneurysm surgery and is therefore a technique anesthesiologists are familiar with. We report the case of a patient who had entered into a coma after cardiac arrest in the postanesthetic recovery unit during central venous catheterization; the patient required 35 minutes of advanced cardiopulmonary resuscitation before heart rhythm and tissue perfusion were restored. The protocol for treating post-cardiac arrest syndrome included therapeutic hypothermia, which was maintained for 12 hours. The patient was extubated after 2 days, with no neurologic deficit. Post-cardiac arrest syndrome is associated with multiple biochemical reactions which are attenuated by hypothermia. Currently available evidence does not allow definitive recommendations regarding the different techniques for inducing therapeutic hypothermia, the ideal temperature to maintain, the duration, or the rewarming process. Further studies are required.     

A critical analysis of outcome for children sustaining cardiac arrest after blunt trauma

Purpose: Injury is the leading cause of cardiac arrest in children older than 1 year. Previous findings suggest that children who require cardiopulmonary resuscitation (CPR) administered by paramedics for any reason rarely survive to hospital discharge. The authors evaluated the outcome of children sustaining cardiac arrest after blunt trauma in a Regional Pediatric Trauma Center. Methods: Children (age [lt ] 16) who underwent CPR in the field or in the emergency department (ED) after blunt trauma were identified from the trauma registry of a regional pediatric trauma center over a 3-year period (1997 to 2000). Patient demographics, rate of survival to discharge, factors influencing survival, and organ donation data were obtained from the trauma registry and medical record. Probability of survival (Ps) was calculated by TRISS analysis. Results: Twenty-five children were identified with a history of cardiac arrest after blunt injury (mean age; 3.3 years; range, 0.1 to 10; mean ISS, 30.7; range, 13-75; mean RTS, 1.58). Mean calculated Ps was 22.7%. However, only 2 (8%) survived. Death in the majority (91%) of the 23 patients who died occurred secondary to brain or spinal cord injury, and only 2 (9%) occurred as the result of exsanguinating hemorrhage. CPR was first performed in the field in 10 patients (40%), en route in 6 (24%), and in the ED in 9 (36%). Of the children who survived, both had vitals in the field, and CPR was administered initially in the ED. Mean length of ED resuscitation before death was 80 minutes. Of the children who died, organ donation occurred in only 3 (13%). The 2 survivors had no head injury and were discharged within 3 weeks of injury. Conclusions: Cardiopulmonary resuscitation after blunt injury in children rarely results in survival. The majority of deaths occur as a result of isolated intracranial injury and not exsanguinating hemorrhage. Although all children should receive aggressive resuscitation after injury, the need for CPR in the field portends a poor outcome. Furthermore, these data would suggest that prolonged or heroic efforts for children sustaining cardiac arrest in the field are not indicated.     

Modes of induced cardiac arrest: hyperkalemia and hypocalcemia - Literature review

The entry of sodium and calcium play a key effect on myocyte subjected to cardiac arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused by hypocalcemia maintains intracellular adenosine triphosphate levels, improves diastolic performance and reduces oxygen consumption, which can be translated into better protection to myocyte injury induced by cardiac arrest.     

Studies of isolated global brain ischaemia: I. Overview of irreversible brain injury and evolution of a new concept - redefining the time of brain death

Despite advanced cardiac life support (ACLS), the mortality from sudden death after cardiac arrest is 85-95%, and becomes nearly 100% if ischaemia is prolonged, as occurs following unwitnessed arrest. Moreover, 33-50% of survivors following ACLS after witnessed arrest develop significant neurological dysfunction, and this rises to nearly 100% in the rare survivors of unwitnessed arrest. Although, whole body (cardiac) survival improves to 30% following recent use of emergency cardiopulmonary bypass, sustained neurological dysfunction remains a devastating and unresolved problem. Our studies suggest that both brain and whole body damage reflect an ischaemic/reperfusion injury that follows the present reperfusion methods that use normal blood, which we term 'uncontrolled reperfusion'. In contrast, we have previously introduced the term 'controlled reperfusion', which denotes controlling both the conditions (pressure, flow and temperature) as well as the composition (solution) of the reperfusate. Following prolonged ischaemia of the heart, lung and lower extremity, controlled reperfusion resulted in tissue recovery after ischaemic intervals previously thought to produce irreversible cellular injury. These observations underlie the current hypothesis that controlled reperfusion will become an effective treatment of the otherwise lethal injury of prolonged brain ischaemia, such as with unwitnessed arrest, and we tested this after 30 min of normothermic global brain ischaemia. This review, and the subsequent three studies will describe the evolution of the concept that controlled reperfusion will restore neurological function to the brain following prolonged (30 min) ischaemia. To provide a familiarity and rationale for these studies, this overview reviews the background and current treatment of sudden death, the concepts of controlled reperfusion, recent studies in the brain during whole body ischaemia, and then summarizes the three papers in this series on a new brain ischaemia model that endorses our hypothesis that controlled reperfusion allows complete neurological recovery following 30 min of normothermic global brain ischaemia. These findings may introduce innovative management approaches for sudden death, and perhaps stroke, because the brain is completely salvageable following ischaemic times thought previously to produce infarction.     

Clinical neuroprotection and secondary neuronal injury mechanisms

Multiple disease processes can ultimately lead to cerebral injury, a common cause of both severe morbidity and mortality in patients of all age groups. Cerebral injury is seen in a variety of both medical and surgical conditions, including stroke, subarachnoid haemorrhage, central nervous system infection, epilepsy, post cardiac arrest and, of course, traumatic brain injury.Although the primary damage to brain tissue may be irreversible, aggressive early physiological, pharmacological and surgical interventions may limit the ensuing secondary brain injury caused by ongoing ischaemia, and reduce the risk of severe disability or death.