Continuing Education Activity

Mortality rates after pediatric cardiac arrest remain high after initial resuscitation and a return of spontaneous circulation. Several factors must be addressed to optimize survival and to prevent subsequent deterioration and/or organ dysfunction and neurologic sequelae. Priorities post-resuscitation include ongoing assessment of the resuscitation and stabilization process, determining and managing the etiology of the arrest, maintain and or minimize brain injury with targeted temperature management and consideration of vasoactive drugs, and preventing decompensation while managing the patient in the emergency department setting, and/or while transporting to a high level of care (pediatric intensive care unit). After a return of spontaneous circulation further stabilization and diagnostic assessments are required. A post-arrest reevaluation includes assessing the adequacy of pulses, perfusion, blood pressure, and adequacy of oxygenation and ventilation. Post-arrest monitoring includes continuous cardiac monitoring, end-tidal carbon dioxide (CO2) measurements, possible brain monitoring, and trending of lab work. Post-arrest patients may be hypotensive, and early and continuous epinephrine infusions are preferred for several reasons. Constant cardiac monitoring is needed to evaluate for the recurrence of precipitating arrhythmias. Ongoing physiology that may lead to arrest must also be addressed, for example hypoxia, acidosis, hypo/hyperkalemia. This activity reviews the evaluation and treatment of post-resuscitation patients and discusses the role of the interprofessional team in managing these patients.

Objectives:

• Identify the features of post cardiac arrest syndrome (PCAS).
• Describe the critical considerations in post-resuscitation management.
• Review what continuous evaluation and monitoring is required post resuscitation.
• Outline the evaluation and treatment of pediatric post-resuscitation patients and summarize the role of the inter-professional team in managing these patients.

Introduction

The pediatric mortality rate following cardiac arrest and return of spontaneous circulation (ROSC) remains greater than 90%.[1] Despite the low overall incidence of cardiac arrest (0.01%) in children, the importance of adequate high-quality care in these scenarios goes without saying. [2]  Several factors regarding pediatric post-resuscitation management need to be addressed in order to optimize patient survival and prevent organ dysfunction.

These factors include determining the etiology of the arrest and managing it appropriately, minimizing neurologic injury, and preventing further clinical decompensation. [1] Additional important considerations include the emotional outcome of the child as well as the immediate and long-term grief experienced by the family. [2] 

The treatment recommendations regarding post-resuscitation management for providers are ever-evolving due to certain barriers in the pediatric population limiting research. The outcome of pediatric CPR is often poor, and can, theoretically, leave care after CPR unnecessary. Additionally, reliable reporting mechanisms and national information archives have historically been inconsistent, if available at all, limiting any meaningful data collection. The recent development of the National Register of Cardiopulmonary Resuscitation, sponsored by the American Heart Association, has facilitated more data collection on this subject, and updates in treatment recommendations. [2] 

The foundation of the 2015 published guidelines by the American Heart Association (AHA) on pediatric post-ROSC management is the prevalence of “post–cardiac arrest syndrome (PCAS)”. [3] This scientific statement is the result of an analysis of the past twenty years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. From this data, it was determined that all resuscitations from cardiac arrest result in predictable sequelae in the days to weeks following the arrest, including neurologic insult, myocardial dysfunction, systemic ischemia, and persistent precipitating pathophysiology. These AHA guidelines as well as other current guidelines highlight PCAS and pay particular attention to morbidity as it relates to temperature regulation and the circulation/perfusion status of patients following cardiac arrest.

Function

Aggressive supportive care is needed during the post-resuscitation phase. [4] Goal-directed therapy is an important aspect of PCAC, and targeting multiple physiological processes, including circulatory support and support of oxygenation and ventilation may be more effective than any single intervention. Despite the significantly high morbidity and mortality resulting from pediatric cardiac arrest, features associated with better prognosis include in-hospital arrest, short duration of arrest, early initiation of CPR, and hypothermia as the cause of arrest. Post-resuscitation hypotension and prolonged duration of CPR have both been predictors of poor prognosis. Thus, management guidelines emphasize preventing hypotension and considering targeted temperature management as well as PCAS on a case-by-case basis. [4] 

Therapeutic Hypothermia and Targeted Temperature Management

Although largely inconclusive, and contradictory at times, there is an abundance of data on targeted temperature management (TTM) in the post-ROSC patient. [5]  In 2012, two landmark trials found a mortality benefit of TTM. [6] In these trials, a targeted temperature of 32–34°C maintained for 12–24 h was associated with improved neurological function and survival. Based on these findings, in 2005, TTM was adopted as a Class I recommendation by the American Heart Association, specifically in the setting of out-of-hospital cardiac arrest (OHCA) due to VF or pulseless ventricular tachycardia (VT). In a recent study in children with OHCA, 38% of those who underwent TTM survived to hospital discharge. Another study found that therapeutic hypothermia in patients with non-shockable initial rhythms was associated with better survival and neurological outcome at hospital discharge than those who did not receive TTM. [7]

Conversely, many studies on therapeutic hypothermia have been inconclusive or failed to show a statistical benefit. [8] In 2017, the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial compared therapeutic hypothermia (33°C) with therapeutic normothermia (36.8°C) after pediatric outside-hospital cardiac arrest (OHCA), and did not show a statistically significant difference in 1-year neurologic outcomes or mortality.[5]  One large trial including 950 patients with OHCA compared a less intensive temperature target (36°C) to traditional TTM (33°C), and found no difference in mortality, suggesting that the mortality benefit from TTM is not dependent upon a specific temperature, rather, the intervention of targeted temperature management itself.

Despite contradicting evidence, and due to the potential for benefit, current guidelines do recommend the use of TTM in both OHCA and IHCA, as well as in cardiac arrest due to shockable or non-shockable rhythms. In clinical practice, TTM can be provided using different methods, including surface-cooling methods (use of ice packs around the body), core-cooling methods (intravenous catheters circulating cold saline) or a combination approach. The 2015 AHA guidelines recommended either to maintain continuous normothermia (TTM to 36°C–37.5°C) for 5 days or to maintain 2 days of continuous hypothermia (TTM to 32C°–34°C) followed by 3 days of continuous normothermia (TTM to 36°C–37.5°C). [3]

During PCAC, fever (≥38°C) should be treated aggressively, as hyperthermia has clearly been associated with increased mortality. Hypothermia is also associated with worse neurologic outcomes, so if TTM is initiated, providers are cautioned to prevent temperatures <32°C.

The best time to initiate TTM has not been determined, and current recommendations suggest considering initiation at the time of ROSC, or arrival to a capable facility. TTM should be maintained consistently for a period of 12–24 hours, and if prolonged patient transport is anticipated, it should be delayed until consistency can be maintained. Sedatives and paralytic agents should be used to ensure comfort and prevent shivering. Analgesia and sedation are best achieved with opiates and/or benzodiazepines. Agents such as rocuronium and vecuronium are commonly used paralytics in pediatrics, and have added oxygenation benefits for patients requiring ventilation. Many institutions have pharmacologic protocols to ensure proper weight-based dosing. Providers must keep in mind that paralytic agents can mask seizures and impede neurological examination. [3] Rewarming should be accomplished slowly at a rate of 0.25–0.5°C/h to avoid hyperthermia.[5]

Despite the current recommendations, much has yet to be definitively studied regarding TTM in pediatric cardiac arrests including the optimal rate of rewarming, the optimal timing of initiation of TTM, the optimal target temperature, and the optimal total duration of TTM.

Perfusion and Hypotension

Perfusion is compromised after cardiac arrest, and patients are often hypotensive. [1]Fluid boluses and inotropic agents should be administered, adhering to situational and facility-based guidelines. [3] One, large, secondary analysis of the THAPCA-IH trial compared survival outcomes based on hypotension. In patients not treated with ECMO, systolic hypotension within six hours of TTM was associated with lower rates of survival to discharge. In the group that did receive ECMO, hypotension was not associated with survival to discharge.[9]

To date no pediatric interventional studies have evaluated the survival effect of manipulating blood pressure after ROSC, however poor perfusion has been obviously associated with increased morbidity and mortality, anecdotally, and per data analysis. Thus, vasoactive drug therapy is recommended, and should be tailored to each patient. There is no recommended blood pressure target, and vasopressors may need to be adjusted to optimize perfusion without creating excessive myocardial work. Early and continuous epinephrine infusion for post-arrest hypotension is the preferred agent in pediatric patients. [10] One retrospective study of 200 patients suggested that epinephrine given within fifteen minutes of arrest (“early epinephrine”) decreased the time to ROSC, and was also associated with a higher survival rate and better neurologic outcomes in children with non-shockable OHCA.  Epinephrine vasoconstricts peripherally, which improves blood pressure, and is also a potent inotropic and chronotropic agent. Dopamine, norepinephrine, and dobutamine also improve blood pressure but are recommended as second-line therapies, or in specific pre-existing conditions such as renal failure or cardiogenic shock.

Oxygenation and Ventilation

Oxygenation and ventilation status is an important piece of post-arrest assessment. [3] It is recommended that providers aim for a normal PaO, keeping in mind pre-existing congenital heart disease or other baseline conditions affecting oxygenation. Preclinical studies suggest that hyperoxia after ROSC can further exacerbate the neurologic injury and should be avoided. The lowest possible fraction of inspired oxygen (FiO2) should be used to maintain an oxygen saturation of 94% to 99%. Hypoxemia should also be avoided whenever possible, as it is associated with higher mortality, particularly in the pediatric population. Oxygenation status should be monitored with continuous cardiac monitoring, continuous pulse oximetry, end-tidal carbon dioxide (ETCO2) measurements, and intermittent (q10-15 minute) arterial blood gasses to guide oxygen titration and support mechanical ventilation.

Arrhythmia

If the etiology of the cardiac arrest is suspected to be arrhythmia, then antiarrhythmic agents such as lidocaine or amiodarone should be considered. [1] Due to optimal drug therapy, in this case, highly dependent on the underlying pathology, pediatric cardiac electrophysiology consultation is strongly recommended, as many antiarrhythmic drugs including amiodarone, procainamide, and sotalol are contraindicated in patients with long-QT syndrome and Brugada syndrome. [3] Of note, arrhythmias are commonly observed during TTM, particularly bradycardia, which usually do not require treatment. Post-resuscitation care includes obtaining and repeating lab studies such as arterial blood gases, electrolytes, or lactate levels if sepsis is suspected. [5]  Further monitoring includes ECG, pulse oximetry, capnography, noninvasive blood pressure measurement, and point-of-care glucose testing.[3]

After perfusion, oxygenation, neurologic, and targeted temperature management goals have been addressed, the patient’s disposition should be considered. Considerations include critical care consultation, facility capabilities, and the need for transfer to a higher level of care, as this may alter or delay the patient’s treatment plan.

Perhaps most importantly, as mentioned above, once TTM is initiated, the target temperature should be maintained consistently for 12-24 hours, without intermittent rewarming, as unintentional or early re-warming has been associated with poor neurologic outcomes compared to patients who did not undergo TTM at all. [5]

Issues of Concern

Neurologic Monitoring

While in the intensive care unit, continuous brain monitoring via electroencephalogram (EEG) can be useful to guide therapy and identify evolving hypoxic-ischemic brain injury and electrographic seizures. Neuroimaging can help identify a cerebral cause of cardiac arrest and assess the degree of severe brain injury.[3]

ECMO

Mechanical circulatory support in the form of extracorporeal membrane oxygenation (ECMO) may be considered during post-cardiac arrest care (PCAC) if significant cardiorespiratory instability persists despite appropriate intervention. 2015 AHA guidelines recommend specifically that ECMO during CPR (ECPR) be considered in the setting of in-hospital cardiac arrest (IHCA) in a pediatric patient with a known cardiac diagnosis. Due to the limited benefit and resource-intensive nature of ECMO, the guidelines caution providers to consider the availability of skilled personnel, protocols, and equipment. Overall, the clinical effectiveness of ECMO after ROSC is inconclusive. Studies indicate ECMO may improve survival for rewarming and circulatory support of cold-water drowning victims. Case series and one study in a PICU population, identified reduced mortality associated with the initiation of ECMO within 24 hours of ROSC in children with refractory cardiogenic shock. If ECMO is initiated during CPR (ECPR), it must be continued during the post-cardiac arrest period until the patient can be separated from mechanical support. [3]

Seizure Management

Acute, electrographic seizures are treated with benzodiazepines, levetiracetam, or phenytoin. Some seizures may be refractory to treatment. Providers must be aware of potential adverse effects of anticonvulsants such as cardiac arrhythmias, hypotension, and respiratory depression, and must take into consideration that any sedation induced by these medications may complicate the neurological examination. [3]

Glucose Management

There is insufficient published evidence to determine the optimal blood glucose concentration during PCAC. During the peri-arrest and post-resuscitation period, providers should promptly identify, prevent, and treat hypoglycemia (≤45 mg/dL in the newborn and ≤60 mg/dL in the child) to avoid further neurologic insult. Additionally, severe hyperglycemia can exacerbate post–cardiac arrest volume depletion and hemodynamic instability, and should be avoided. [3]

Prognosis and Imaging Considerations

Brain CT is useful to identify treatable intracranial causes of cardiac arrest, but is not reliable for neuroprognostication. Brain MRI after ROSC may be helpful, along with serial neurological examinations, EEG, and other adjuncts to estimate the extent of neurological recovery. [3]

Clinical Significance

Greater than 5000 children experience OHCA annually in the United States, with ROSC rates of approximately 36%. Overall survival rates from 2005 to 2013 data collection range from only 6.4% to 10.2%. [8] Surprisingly, despite changes in post-resuscitation management recommendations, survival to hospital discharge after OHCA has not significantly changed over the past 10 years. However, the favorable neurological outcome has improved and is now reported in as many as 77% of pediatric OHCA survivors.[3] Studies have shown a mortality benefit associated with TTM, ECMO in the appropriate setting (IHCA and cold-water drowning), and IHCA (37%) versus OHCA (16%). Unfortunately, a majority of patients die in the post-cardiac arrest period, before hospital discharge, and the majority of survivors of pediatric cardiac arrest sustain short- and long-term neurologic morbidities.

Factors for all ages that are associated with a better prognosis after cardiac arrest include a short duration of arrest, early initiation of CPR, hypothermia as the cause of arrest, and IHCA. Factors associated with unfavorable neurologic outcomes from OHCA are decreased age, sudden infant death syndrome, and blunt trauma. Factors associated with decreased survival after IHCA include older age, pre-existing conditions, interventions such as tracheal intubation, mechanical ventilation, and use of vasopressors at the time of arrest, and arrests occurring during night and weekend shifts. [3] For both OHCA and IHCA, pre-arrest rhythms of bradycardia and VF/VT were associated with the highest survival, and pulseless electrical activity (PEA) was associated with higher survival than asystole.

Post–cardiac arrest brain injury and myocardial dysfunction are the leading causes of morbidity and mortality in children. [8] Clinical manifestations of brain injury after arrest include coma, cerebral edema, seizures, myoclonus, sympathetic hyperarousal, and long-term neurobehavioral deficits. Myocardial dysfunction develops in approximately two-thirds of patients after ROSC, and may subsequently improve. [3]

The 2015 AHA guidelines recommend the time to prognosticate neurological outcomes in patients not treated with TTM is 72 hours after ROSC. The guidelines recommend up to 5 days for patients treated with TTM.[3] Additionally, there is no definite marker to determine the futility of CPR.

Other Issues

Cardiac Arrest Caused by Drowning

Drowning causes up to 31% of all pediatric OHCA, and survival rates range from 9% to 46%. [11] As noted, children with cardiac arrest from drowning have better outcomes overall when compared with children with other respiratory causes of arrest. In a review of 198 children who received ECMO after a drowning event between 1986 and 2015, survival was 54%, much higher than the less than 10% average survival rate after pediatric cardiac arrest. [3]

Longer duration of submersion and longer duration of CPR are associated with poor neurological outcomes. Therapeutic hypothermia has not been shown to provide any statistically significant neurologic benefit in drowning victims when compared to normothermia protocols. Several case series describe patients successfully decannulated from ECMO with favorable neurological outcomes. There is currently insufficient published data to identify management recommendations specific to drowning-associated cardiac arrest. In these cases, clinicians are encouraged to use the general approach to PCAC as described above. 

Patient and Caregiver Outcomes

Survivors of cardiac arrest can have significant dysfunction, and parents of child survivors often report limitations in their daily activities. Long-term neurobehavioral and neuropsychiatric outcomes vary from patient to patient, and some may actually improve over time. Further assessment of these outcomes and the long-term burden on survivors and their families will allow us to determine whether improvements in CPR quality and PCAC are improving the long-term outcomes.

Organ Donation

Two situations that make for potential organ donation are donation after neurologic death and donation after circulatory death. [12] Donation after the neurological death requires a multidisciplinary approach of caregivers, involving ethics committee consultation, patient's caregivers, social workers, clergy, nursing, and pediatric neurology and critical care providers. Donation after circulatory determination of death are commonly encountered in emergency departments and include cases of SIDS, sepsis, abusive, or accidental trauma. It is preferred to defer any discussion involving the potential for organ donation to your local organ procurement organization.

COVID and Cardiac Arrest

Strict adherence to personal protective equipment (PPE) is paramount when caring for cardiac arrest patients presenting to emergency departments during the current COVID pandemic. The CDC has guidelines to assist practitioners in the proper means of donning and doffing PPE. Extra precautions should be taken when involved in aerosolizing procedures and intubation.

Multi-disciplinary Approach and Debriefing

The local medical examiner, organ donation services, and in some cases child protective services may be involved. The American Heart Association (AHA) also emphasizes the role and importance of debriefing with staff and members of the clinical team, post-resuscitation.

Enhancing Healthcare Team Outcomes

Post- cardiac arrest resuscitation is usually begun in the emergency department, and, if the patient survives, is continued in the ICU setting. The resuscitation is resource-intensive and involves a large interprofessional team including neurologists, intensivists, primary care providers, ICU nurses, social workers, ethics teams, organ donation teams, possibly child protective services, and clergymen. Because many patients do not survive cardiac arrest, and many have a poor prognosis, open communication with the family is important. An ethics team as well as bereavement support should be involved with the family early on. Children who survive cardiac arrest are often left with anoxic brain damage, and face numerous problems with daily living, so all outcomes should be explained in detail to family. Frequent communication and updates by the clinical team can help prepare the family if there is no hope for salvage. The local organ donation organization should be contacted as soon as the patient's prognosis is determined to be poor, as the family may need time to process these decisions. A multidisciplinary approach should be employed in all cases, as they often exhaust resources, cause increased stress for providers, and are emotionally taxing for all involved.