Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest.

Cardiac arrest is the most common cause of death in North America. An organized bundle of neurocritical care interventions can improve chances of survival and neurological recovery in patients who are successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Key aspects of successful early post-arrest management include: prevention of secondary brain injury; identification of treatable causes of arrest in need of emergent intervention; and, delayed neurological prognostication. Secondary brain injury can be attenuated through targeted temperature management (TTM), avoidance of hypoxia and hypotension, avoidance of hyperoxia, hyperventilation or hypoventilation, and treatment of seizures. Most patients remaining comatose after resuscitation from cardiac arrest should undergo TTM. Treatable precipitants of arrest that require emergent intervention include, but are not limited to, acute coronary syndrome, intracranial hemorrhage, pulmonary embolism and major trauma. Accurate neurological prognostication is generally not appropriate for several days after cardiac arrest, so early aggressive care should never be limited based on perceived poor neurological prognosis.

Ultrarapid Induction of Hypothermia Using Continuous Automated Peritoneal Lavage With Ice-Cold Fluids: Final Results of the Cooling for Cardiac Arrest or Acute ST-Elevation Myocardial Infarction Trial.

OBJECTIVES: Hypothermia (32-34 °C) can mitigate ischemic brain injury, and some evidence suggests that it can reduce infarct size in acute myocardial infarction and acute ischemic stroke. For some indications, speed of cooling may be crucial in determining efficacy. We performed a multicenter prospective intervention study to test an ultrarapid cooling technology, the Velomedix Automated Peritoneal Lavage System using ice-cold fluids continuously circulating through the peritoneal cavity to rapidly induce and maintain hypothermia in comatose patients after cardiac arrest and a small number of awake patients with acute myocardial infarction. DESIGN: Multicenter prospective intervention study. SETTING: Intensive care- and coronary care units of multiple tertiary referral centers. MEASUREMENTS AND MAIN RESULTS: Access to the peritoneal cavity was gained using a modified blunt dilating instrument, followed by catheter placement. Patients were cooled to a temperature of 32.5 °C, maintained for 24 hours (cardiac arrest) or 3 hours (acute myocardial infarction) followed by controlled rewarming. Forty-nine patients were enrolled, and 46 patients completed treatment. One placement was unsuccessful (abdominal wall not breached), two patients were ultimately not cooled, and only safety data are reported. Average catheter insertion time was 2.3 minutes. Mean time to temperature less than 33 °C was 10.4 minutes (average cooling rate, 14 °C/hr). Median infarct size in patients who had coronary interventions was 16% of LV. No cases of stent thrombosis occurred. Survival in cardiac arrest patients with initial rhythm of ventricular tachycardia/ventricular fibrillation was 56%, of whom 82 had a complete neurologic recovery. This compares favorably to outcomes from previous studies. CONCLUSION: Automated peritoneal lavage system is a safe and ultrarapid method to induce and maintain hypothermia, which appears feasible in cardiac arrest patients and awake patients with acute myocardial infarction. The shivering response appeared to be delayed and much reduced with this technology, diminishing metabolic disorders associated with cooling and minimizing sedation requirement. Our data suggest that ultrarapid cooling could prevent subtle neurologic damage compared with slower cooling. This will need to be confirmed in direct comparative studies.

What is the right temperature to cool post-cardiac arrest patients?

CITATION: Niklas Nielsen, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369:2197-206. doi: 10.1056/NEJMoa1310519 . Epub 2013 Nov 17. Pub Med PMID: 20089970. BACKGROUND: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome. OBJECTIVE: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures. DESIGN: A multicenter, international, open label, randomized controlled trial. SETTING: Thirty-six ICUs in Europe and Australia participated in this study. PARTICIPANTS: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions). INTERVENTION: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours. OUTCOMES: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied. RESULTS: Out of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87). CONCLUSIONS: Maintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.

Neuroprotection in acute brain injury: an up-to-date review.

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

Do not drown the patient: appropriate fluid management in critical illness.

Administering intravenous fluids to support the circulation in critically ill patients has been a mainstay of emergency medicine and critical care for decades, especially (but not exclusively) in patients with distributive or hypovolemic shock. However, in recent years, this automatic use of large fluid volumes is beginning to be questioned. Analysis from several large trials in severe sepsis and/or acute respiratory distress syndrome have shown independent links between volumes of fluid administered and outcome; conservative fluid strategies have also been associated with lower mortality in trauma patients. In addition, it is becoming ever more clear that central venous pressure, which is often used to guide fluid administration, is a completely unreliable parameter of volume status or fluid responsiveness. Furthermore, 2 recently published large multicenter trials (ARISE and ProCESS) have discredited the "early goal-directed therapy" approach, which used prespecified targets of central venous pressure and venous saturation to guide fluid and vasopressor administration. This article discusses the risks of "iatrogenic submersion" and strategies to avoid this risk while still giving our patients the fluids they need. The key lies in combining good clinical judgement, awareness of the potential harm from excessive fluid use, restraint in reflexive administration of fluids, and use of data from sophisticated monitoring tools such as echocardiography and transpulmonary thermodilution. Use of smaller volumes to perform fluid challenges, monitoring of extravascular lung water, earlier use of norepinephrine, and other strategies can help further reduce morbidity and mortality from severe sepsis.

Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest.

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including targeted temperature management (TTM), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an emergency neurological life support protocol. Patients remaining comatose following resuscitation from cardiac arrest should be considered for TTM. This protocol will review induction, maintenance, and re-warming phases of TTM, along with management of TTM side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography and/or magnetic resonance imaging of the brain, continuous electroencephalography monitoring, and correction of electrolyte, blood gas, and hematocrit changes, are also necessary to optimize outcomes.

Of ions and temperature: the complicated interplay of temperature, fluids, and electrolytes on myocardial function.

This article discusses the potential of levosimendan to treat calcium-induced myocardial dysfunction associated with deep hypothermia. Moderate hypothermia (30 to 34°C) usually improves myocardial contractility and stabilizes heart rhythm, but deep hypothermia can cause severe myocardial dysfunction, which is mediated by intracellular calcium overload. In experimental studies, levosimendan appears effective in reversing this. Clinical studies are needed to confirm these findings and to determine whether levosimendan could also be used for accidental hypothermia and perhaps to mitigate diastolic dysfunction under moderate hypothermia.

Automated peritoneal lavage: an extremely rapid and safe way to induce hypothermia in post-resuscitation patients.

INTRODUCTION: Mild therapeutic hypothermia (MTH) is a worldwide used therapy to improve neurological outcome in patients successfully resuscitated after cardiac arrest (CA). Preclinical data suggest that timing and speed of induction are related to reduction of secondary brain damage and improved outcome. METHODS: Aiming at a rapid induction and stable maintenance phase, MTH induced via continuous peritoneal lavage (PL) using the Velomedix Inc. automated PL system was evaluated and compared to historical controls in which hypothermia was achieved using cooled saline intravenous infusions and cooled blankets. RESULTS: In 16 PL patients, time to reach the core target temperature of 32.5°C was 30 minutes (interquartile range (IQR): 19 to 60), which was significantly faster compare to 150 minutes (IQR: 112 to 240) in controls. The median rate of cooling during the induction phase in the PL group of 4.1°C/h (IQR: 2.2 to 8.2) was significantly faster compared to 0.9°C/h (IQR: 0.5 to 1.3) in controls. During the 24-hour maintenance phase mean core temperature in the PL patients was 32.38 ± 0.18°C (range: 32.03 to 32.69°C) and in control patients 32.46 ± 0.48°C (range: 31.20 to 33.63°C), indicating more steady temperature control in the PL group compared to controls. Furthermore, the coefficient of variation (VC) for temperature during the maintenance phase was lower in the PL group (VC: 0.5%) compared to the control group (VC: 1.5%). In contrast to 23% of the control patients, none of the PL patients showed an overshoot of hypothermia below 31°C during the maintenance phase. Survival and neurological outcome was not different between the two groups. Neither shivering nor complications related to insertion or use of the PL method were observed. CONCLUSIONS: Using PL in post-CA patients results in a rapidly reached target temperature and a very precise maintenance, unprecedented in clinical studies evaluating MTH techniques. This opens the way to investigate the effects on neurological outcome and survival of ultra-rapid cooling compared to standard cooling in controlled trials in various patient groups. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01016236

Emergency neurological life support: resuscitation following cardiac arrest.

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including therapeutic hypothermia (TH), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Patients remaining comatose following resuscitation from cardiac arrest and who are not bleeding are potential candidates for TH. This protocol will review induction, maintenance, and re-warming phases of TH, along with management of TH side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography imaging of the brain, continuous electroencephalography, monitoring, and correction of electrolyte, blood gas, and hematocrit changes are also necessary to optimize outcomes.

Consensus recommendations on therapeutic hypothermia after minimally invasive intracerebral hemorrhage evacuation from the hypothermia for intracerebral hemorrhage (HICH) working group.

Background and purpose: Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation. Methods: An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion. Results: These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy. Conclusions: These recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population.

Feasibility of early waking cardiac arrest patients whilst receiving therapeutic hypothermia: The therapeutic hypothermia and early waking (THAW) trial.

AIM: To determine the safety and feasibility of an early (12 h) waking and extubation protocol for out-of-hospital cardiac arrest (OHCA) patients receiving targeted temperature management (TTM). METHODS: This was a single-centre, prospective, non-randomised, observational, safety and feasibility pilot study which included successfully resuscitated OHCA patients, of presumed cardiac cause. Inclusion criteria were: OHCA patients aged over 18 years with a return of spontaneous circulation, who were going to receive TTM33 (TTM at 33 °C for 24 h and prevention of hyperthermia for 72 h) as part of their post cardiac arrest care. Clinical stability was measured against physiological and neurological parameters as well as clinical assessment. RESULTS: 50 consecutive patients were included (median age 65.5 years, 82% male) in the study. Four (8%) patients died within the first twelve hours and were excluded from the final cohort (n = 46). Twenty-three patients (46%) were considered clinically stable and suitable for early waking based on the intention to treat analysis; 12 patients were extubated early based on a variety of clinical factors (21.4 ± 8.6 h) whilst continuing to receive TTM33 with a mean core temperature of 34.2 °C when extubated. Of these, five patients were discharged from the intensive care unit (ICU) <48 h after admission with a mean ICU length of stay 1.8 ± 0.4 days. Twenty-eight patients (56%) were discharged from the ICU with a modified Rankin Score of 0-2. The overall intra-hospital mortality was 50% (n = 25). CONCLUSIONS: It is safe and feasible to wake selected comatose OHCA patients at 12 h, allowing for earlier positive neuro-prognostication and reduced ICU stay.

Hypothermia, immune suppression and SDD: can we have our cake and eat it?

In vitro studies and clinical observations suggest that both accidental and controlled/therapeutic hypothermia have a strong immunosuppressive effect, and that hypothermia increases the risk of infections, especially wound infections and pneumonia. In the previous issue of Critical Care, Kamps and colleagues report that when hypothermia was used for prolonged periods in patients with severe traumatic brain injury in conjunction with selective decontamination of the digestive tract, the risks of infection were the same or lower in patients treated with therapeutic cooling. The risk of infection is widely regarded as the most important danger of therapeutic cooling. The findings of Kamps and colleagues need to be verified in prospective trials and in higher-resistance environments, but raise the possibility of cooling for prolonged periods with greatly reduced risk. We may be able to have our cake and eat it.

An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: an international consensus conference in intensive care medicine.

OBJECTIVES: To address the issues of Prevention and Management of Acute Renal Failure in the ICU Patient, using the format of an International Consensus Conference. METHODS AND QUESTIONS: Five main questions formulated by scientific advisors were addressed by experts during a 2-day symposium and a Jury summarized the available evidence: (1) Identification and definition of acute kidney insufficiency (AKI), this terminology being selected by the Jury; (2) Prevention of AKI during routine ICU Care; (3) Prevention in specific diseases, including liver failure, lung Injury, cardiac surgery, tumor lysis syndrome, rhabdomyolysis and elevated intraabdominal pressure; (4) Management of AKI, including nutrition, anticoagulation, and dialysate composition; (5) Impact of renal replacement therapy on mortality and recovery. RESULTS AND CONCLUSIONS: The Jury recommended the use of newly described definitions. AKI significantly contributes to the morbidity and mortality of critically ill patients, and adequate volume repletion is of major importance for its prevention, though correction of fluid deficit will not always prevent renal failure. Fluid resuscitation with crystalloids is effective and safe, and hyperoncotic solutions are not recommended because of their renal risk. Renal replacement therapy is a life-sustaining intervention that can provide a bridge to renal recovery; no method has proven to be superior, but careful management is essential for improving outcome.

Care After REsuscitation: Implementation of the United Kingdom's First Dedicated Multidisciplinary Follow-Up Program for Survivors of Out-of-Hospital Cardiac Arrest.

Survival rates after cardiac arrest (CA) are increasing, with more patients and their families living with the psychological consequences of surviving a sudden CA. The currently available neuropsychological assessment tools and therapies were not designed for CA, and may be inadequate. The Essex Cardiothoracic Centre set up the United Kingdom's first dedicated multidisciplinary "Care After REsuscitation" (CARE) service, offering CA survivors and their caregivers systematic psychological, cognitive, and specialized medical support for the first 6 months after CA. Twenty-one patients were recruited into the CARE pilot service evaluation. Patients' health at hospital discharge was poor; however, by 6 months all components (except general health) had improved significantly, and were close to that experienced by "healthy" individuals. Five (26%) required referral to a psychiatrist, with all 5 (26%) subsequently being diagnosed with moderate-to-severe depression, and 3 (16%) with comorbid post-traumatic stress disorder. Our study demonstrates a large unmet clinical need in general and neuropsychological assessment, and our results suggest that offering appropriate and prompt specialist diagnosis and therapies leads to an improvement in health at 6 months.

Systematic review and meta-analysis of intravascular temperature management vs. surface cooling in comatose patients resuscitated from cardiac arrest.

OBJECTIVE: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) vs. surface cooling methods (SCM) for induced hypothermia (IH). METHODS: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods. ELIGIBILITY: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM vs. SCM were eligible for inclusion. RESULTS: In total, 12 studies met inclusion criteria. These enrolled 1573 patients who received IVTM; and 4008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI -1%, 5%)]. Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM vs. SCM. There was no significant difference in other evaluated adverse events between groups. CONCLUSIONS: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest.