Therapeutic Hypothermia For Cardiac Arrest Research Articles

Association of time-temperature curves with outcomes in temperature management for cardiac arrest

Background/PurposeCardiac arrest is a common cause of death and neurological injury; therapeutic cooling for neuroprotection is standard of care. Despite numerous and ongoing trials targeting a specified cooling temperature for...

Letter to the Editor: From Target Temperature Management Trial 1 to Trial 2: Therapeutic Hypothermia for Cardiac Arrest Discredited?

Letter to the Editor: From Target Temperature Management Trial 1 to Trial 2: Therapeutic Hypothermia for Cardiac Arrest Discredited?

Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest

Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed. The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status. SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome. Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013). Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.

Therapeutic hypothermia for cardiac arrest due to non-shockable rhythm: A protocol for systematic review and meta-analysis.

Background:The effectiveness of therapeutic hypothermia (TH) for patients following cardiac arrest with non-shockable rhythm is debated. We plan to conduct a systematic review and meta-analysis with all available randomized controlled trials (RCTs) to explore the efficacy and safety of TH in in this population.Methods:PubMed, EMBASE and Cochrane Library will be searched to identify RCTs published from inception through December 2020 without language restriction. Patients following cardiac arrest due to non-shockable rhythm will be included. The primary outcome is the hospital mortality. The secondary outcome is the favorable neurological outcome. The pooled effects will be analyzed as mean differences using the inverse-variance method for continuous data or as risk ratios using the Mantel–Haenszel method for dichotomous data. Subgroup and sensitivity analyses will be conducted. The Egger's test and/or the funnel plot will be used to test the publication bias. The grades of recommendation assessment, development, and evaluation (GRADE) methodology will be used to assess the quality of evidence. The trial sequential analysis will be used to test whether the meta-analysis is conclusive.Results:The RCTs on the effectiveness of TH for patients following cardiac arrest with non-shockable rhythm will be systematically reviewed and advance evidence will be provided.Conclusion:Advanced evidence of TH for cardiac arrest due to non-shockable rhythm will be provided for physicians.PROSPERO registration number:CRD42020161823.

P0250COLD DIURESIS DURING TARGETED TEMPERATURE MANAGEMENT AFTER CARDIAC ARREST, MYTH OR FACT?

Abstract Background and Aims Therapeutic hypothermia or targeted temperature management (TTM) has been standard treatment for cardiac arrest survivors with suspected hypoxic ischemic brain injury for improvement in both survival and neurological outcomes. TTM is consisted of an induction phase of quickly lowering the temperature to target temperature (ranging from 32°C -36°C) as soon as possible, a hypothermia maintenance phase of keeping the body temperature at target temperature for at least 24 hours, a rewarming phase of slowly rewarming the temperature to normothermia, and a normothermia phase of keeping the body temperature at normothermia. During the dynamic changes in body temperature, cold-diuresis is a commonly described phenomenon. However, limited studies have characterized cold-induced diuresis during TTM. In this study, we sought to determine urine output changes during post cardiac arrest therapeutic hypothermia. Method This retrospective cohort study included adult patients who underwent TTM after out-of-hospital cardiac arrest and were admitted to the intensive care unit for post cardiac arrest care between January 2012 and August 2018. The exclusion criteria of this study were as follows: 1) deceased status before the completion of all phase of TTM; 2) previous end stage kidney disease patients, 3) undergoing renal replacement therapy due to AKI within 48 hours of TTM termination; 4) terminal cancer less than 6 months of life expectancy or previously cerebral performance category (CPC) 3 or more. The neurologic outcome was assessed using the CPC score after 1 month. Good neurologic outcome was defined as a CPC score of 1, 2 and poor neurologic outcome as a CPC score of 3 to 5. The post cardiac arrest protocol recommends a target temperature of 33°C unless the patient is hemodynamically unstable or has a bleeding tendency or severe infection. Rewarming rate was 0.15°C/hr or 0.25°C/hr. TTM was conducted with the use of temperature managing devices with a feedback loop system (Artic Sun Energy Transfer Pads, Medivance Corp., Louisville, CO, USA; Cool Guard Alsius Icy Heat Exchange Catheter, Alsius Corporation, Irvine, CA, USA). We calculated the hourly IV fluid input and urine output rates for each TTM phase. To compare the mean of urine volume between each TTM phase, we used repeated measure analysis of variance (ANOVA). Results 178 Patients included in the analysis. We observed a increase in urine output rates during hypothermia induction. This effect persisted even after adjustment for variable clinical confounders, including intravenous fluid input rate, mean arterial pressure (MAP), initial shockable rhythm, SOFA score, body mass index, and IV furosemide use. However, we did not detect any evidence of urine output increases or decreases during the hypothermia maintenance or rewarming phases. By repeating measures ANOVA and a linear mixed model, it was confirmed that there is a difference in urine output for each TTM phase. Even after the post hoc analysis was calibrated with several variables, only the hypotheria induction phase differed significantly from the urine output of the phase. Conclusion Although our results are some limitations, the findings support the potential presence of cold-induced dieresis, but not rewarm anti-diuresis during TTM. Our study may not fully capture the extent of renal impairment in post cardiac arrest undergoing TTM. However, our objective was to characterize urine output during TTM in post cardiac arrest patients. This has important implications for fluid management in patients undergoing TTM.

Still No Benefit from Prehospital Initiation of Therapeutic Hypothermia for Cardiac Arrest

Therapeutic hypothermia is recommended for patients with return of spontaneous circulation (ROSC) after cardiac arrest. Animal studies suggest that

National Trends in Utilization of Therapeutic Hypothermia for Cardiac Arrest: National Inpatient Sample Study 2008–2014 (P2.9-070)

National Trends in Utilization of Therapeutic Hypothermia for Cardiac Arrest: National Inpatient Sample Study 2008–2014 (P2.9-070)

Neurologic consultation and use of therapeutic hypothermia for cardiac arrest

ObjectiveTo determine whether neurologic consultation influences the use of therapeutic hypothermia. MethodsWe identified adult patients treated for cardiac arrest from October 2009 through September 2015 at 149 academic medical centers and their affiliate hospitals using discharge diagnosis codes in Vizient database. Neurology consultation was defined as a neurologist participating in patient care at any point during the hospitalization. Use of therapeutic hypothermia was identified using procedure codes. We used multivariable models to evaluate the association between neurologic consultation and therapeutic hypothermia before and after adjustment for patient baseline characteristics and hospital factors including inpatient volume and relative volume of cardiac arrest cases. ResultsWe identified 136,830 hospitalizations for cardiac arrest. The 9,336 (6.8%) encounters involving a neurologist had higher severity of illness, longer hospital stay, and longer intensive care unit stay. There were 5,034 (3.7%) encounters where patients underwent therapeutic hypothermia. Hypothermia use was significantly more common when neurologists were involved during hospitalization (7.9% vs. 3.4%; OR 2.44, 95% CI 2.2-2.6; p<0.01). After adjustment, neurologic consultation continued to be associated with the use of therapeutic hypothermia (adjusted OR 2.5, 95% CI 2.3–2.8), particularly among hospitals in the highest quartile of total inpatient volume (OR 4.6, 95% CI 4.0–5.3). Lower in-hospital mortality was also associated with neurological consultation after adjusting for therapeutic hypothermia (59.2% vs. 61.3%, p<0.01). ConclusionsThe involvement of a neurologist in cardiac arrest patients is associated with increased use of therapeutic hypothermia, though therapeutic hypothermia for cardiac arrest likely remains underutilized.

Rapid Induction of Therapeutic Hypothermia Using Transnasal High Flow Dry Air.

Early induction of therapeutic hypothermia (TH) is recommended in out-of-hospital cardiac arrest (CA); however, currently no reliable methods exist to initiate cooling. We investigated the effect of high flow transnasal dry air on brain and body temperatures in adult porcine animals. Adult porcine animals (n = 23) under general anesthesia were subject to high flow of transnasal dry air. Mouth was kept open to create a unidirectional airflow, in through the nostrils and out through the mouth. Brain, internal jugular, and aortic temperatures were recorded. The effect of varying airflow rate and the air humidity (0% or 100%) on the temperature profiles were recorded. The degree of brain cooling was measured as the differential temperature from baseline. A 10-minute exposure of high flow dry air caused rapid cooling of brain and gradual cooling of the jugular and the aortic temperatures in all animals. The degree of brain cooling was flow dependent and significantly higher at higher airflow rates (0.8°C ± 0.3°C, 1.03°C ± 0.6°C, and 1.3°C ± 0.7°C for 20, 40, and 80 L, respectively, p < 0.05 for all comparisons). Air temperature had minimal effect on the brain cooling over 10 minutes with similar decrease in temperature at 4°C and 30°C. At a constant flow rate (40 LPM) and temperature, the degree of cooling over 10 minutes during dry air exposure was significantly higher compared to humid air (100% saturation) (1.22°C ± 0.35°C vs. 0.21°C ± 0.12°C, p < 0.001). High flow transnasal dry air causes flow dependent cooling of the brain and the core temperatures in intubated porcine animals. The mechanism of cooling appears to be evaporation of nasal mucus as cooling is mitigated by humidifying the air. This mechanism may be exploited to initiate TH in CA.

Temperature Control in Rodent Neuroprotection Studies: Methods and Challenges.

Extensive animal research facilitated the clinical translation of therapeutic hypothermia for cardiac arrest in adults and hypoxic-ischemic injury in infants. Similarly, clinical interest in hypothermia for other brain injuries, such as stroke, has been greatly supported by positive findings in preclinical work. The reliability, validity, and utility of animal models, among many research practices (blinding, randomization, etc.), are key to successful clinical translation. Here, we review methods used to induce and maintain hypothermia in animal models. These include physical and pharmacological methods. We emphasize the advantages and limitations of each approach, and the importance of using clinically relevant cooling protocols and appropriate monitoring and reporting approaches. Moreover, we performed a literature survey of ischemic stroke studies published in 2015 to highlight the continuing risk of temperature confounds in neuroprotection studies. For example, many still do not accurately monitor and report temperature during surgery (23.5%), even though almost half of these studies (46.0%) use pharmaceutical agents that likely influence temperature. We hope this review stimulates awareness and discussion of the importance of temperature in neuroprotective studies.

Comparison of Outcomes Between Patients Treated by Therapeutic Hypothermia for Cardiac Arrest Due to Cardiac or Respiratory Causes

Outcome for patients experiencing out-hospital cardiac arrest (OHCA) due to respiratory causes is poor, even with treatment by therapeutic hypothermia (TH). The purpose of this study is to clarify difference in outcome and respiratory state during resuscitation between cases due to respiratory causes versus those due to cardiac causes, to establish alternative strategies for the patient. This study was conducted as a retrospective analysis of patients with post CA syndrome who underwent TH. Patients were divided into two groups according to cause of CA: cardiac (C group) or respiratory (R group). Utstein Style data, outcome, and arterial blood gas (ABG) findings after emergency room admission of the two groups were compared. Of 74 patients treated with TH during the 2-year study period, 49 were placed in the C group and 19 in the R group. The rates of ventricular fibrillation/pulseless ventricular tachycardia at initial rhythm were significantly higher in the C group than in the R group. The rate of favorable neurological outcome was significantly higher in the C group (15/49: 30.6%) than in the R group (1/19: 5.3%) 30 days after resuscitation. In the ABG findings, PaCO2 was significantly higher in the R group than in the C group. For patients experiencing OHCA from respiratory causes, TH was less effective and PaCO2 accumulated immediately after admission. From this, interpretation of the significance of PaCO2 in these patients at the early stage after return of spontaneous circulation should be seriously considered.

Evaluation of glucose management during therapeutic hypothermia at a Tertiary Academic Medical Center

Study aimAlterations in metabolic function during therapeutic hypothermia (TH) decrease responsiveness to insulin and increase the risk of hyperglycemia. Glycemic control is associated with improved outcomes in selected patients; however, glycemic management strategies during TH are not defined. The objective of this analysis was to evaluate the glycemic metrics and IV insulin administration in critically ill patients during the cooling and rewarming phases of TH. MethodsData from 37 patients who received at least 6h of therapeutic hypothermia for cardiac arrest between January 2007 and January 2010 were retrospectively evaluated, 14 (37.8%) of whom had diabetes. ResultsThe mean blood glucose was 9.16±3.22mmol/L and 6.54±2.45mmol/L; p<0.01 during cooling and rewarming, respectively. Twelve (32.4%) patients experienced at least one hypoglycemic event, defined as a blood glucose <4mmol/L. Nineteen (51.4%) patients experienced at least one hyperglycemic event, defined as a blood glucose >11.11mmol/L and 15 (40.5%) patients received IV insulin therapy. Patients on IV insulin had a higher incidence of diabetes (9 vs. 5; p<0.05), higher admission blood glucose (13.89±6.13 vs. 11.03±4.65mmol/L; p=0.11), and a higher incidence of hyperglycemia (14 vs. 2; p<0.01) and hypoglycemia (8 vs. 4; p<0.05). Of the patients on IV insulin, mean insulin requirements during cooling and rewarming were 15.2±16.1 and 7±12.5units/h, respectively. ConclusionTH is commonly associated with hyperglycemia, hypoglycemia, and the use of IV insulin therapy. Further research is needed to determine optimal glycemic management strategies to prevent hyper- and hypoglycemia in patients during the different phases of TH.

National trends in the use of postcardiac arrest therapeutic hypothermia and hospital factors influencing its use.

Therapeutic hypothermia (TH) in cardiac arrest continues to be underused in the United States. A better understanding of its utilization could inform future efforts and policies to improve utilization. This study investigates trends in TH use for in and out-of-hospital cardiac arrest, and hospital factors associated with its use. We performed a cross-sectional analysis using the Nationwide Inpatient Sample (NIS), 2007-2010, of US adult hospitalizations with cardiac arrest. Annual rates of TH use and proportions of hospitals using TH were calculated using NIS weighting. Potential hospital factors associated with increased likelihood of TH utilization were assessed using logistic regression. Across 2007-2010, 1.35% of cardiac arrest patients received TH; increasing from 0.34% (2007) to 2.49% (2010). The proportion of hospitals using TH was 13.63%, increasing from 4.63% (2007) to 22.16% (2010). Significant hospital factors associated with TH utilization were: large hospitals, urban location, Northeast or West regions, teaching hospitals, non-safety net hospitals, increasing year, and hospitals with higher annual cardiac arrest volume. Utilization of TH in cardiac arrest remains low, but increased sevenfold from 2007 to 2010. The significant variability in implementation of TH, argues for nationwide best practices or regionalization of postcardiac arrest care hospitals.

Therapeutic hypothermia in cardiac arrest and ventilation-associated pneumonia: Our 6 years experience on SDD protocol

Purpose of the study: Therapeutic hypothermia (TH) improves neurological outcome after cardiac arrest (CA) but may yield an increased risk of infection.1,2 Davies et al.3 reported increased survival when patients treated with TH after out-of-hospital CA were given early systemic antibiotics when compared to those patients who received late antibiotics. The reported ventilator associated pneumonia (VAP) rate in the literature, in non-TH patients, ranges from 9% to 27%.4 The VAP rate in TTM trial5 was 21.22% both for normothermic and hypothermic patients.

Serotonin syndrome after therapeutic hypothermia for cardiac arrest: A case series

AimTo describe causes, manifestations, and diagnosis of serotonin syndrome following therapeutic hypothermia (TH) after cardiac arrest. MethodsRetrospective case series from a tertiary academic medical center. ResultsThree male patients suffered witnessed out-of-hospital cardiac arrests and were treated with induced TH. Initial cardiac rhythms included asystole in two and ventricular fibrillation in one. Following completion of rewarming, all three developed neurological signs unexpected for their clinical condition. These included rigidity, hyperreflexia, diffuse tremors, ankle clonus, and marked agitated delirium. Patients also were febrile, hypertensive, and tachycardic. A diagnosis of serotonin syndrome was made in all cases and serotonergic medications were discontinued. All three patients recovered consciousness and two made a full neurological recovery. One patient remained dependent on others for activities of daily living at the time of hospital discharge because of short-term memory impairment. ConclusionsUnexpected neurologic findings and prolonged high fever following recovery from TH can be manifestations of serotonin syndrome rather than post-cardiac arrest anoxic brain injury.

Intact neurological status after induced therapeutic hypothermia in cardiac arrest

Introduction: Cardiac arrest patients in whom return of spontaneous circulation (ROSC) is achieved after resuscitation frequently develop irreversible neurological impairments owing to hypoxic injury and reperfusion induced cell death. Therapeutic hypothermia has become a standard strategy in specific unconscious adult patients with ROSC after out-of-hospital cardiac arrest (OHCA) as per American Heart Association (AHA) guidelines. Case Report: A 48-year-old South Asian male arrived to our emergency department with 20 minutes duration of OHCA with no basic life support (BLS) measures en route to hospital. His initial rhythm was ventricular fibrillation and he had ROSC after 13 minutes of cardiopulmonary resuscitation (CPR) and subsequently underwent therapeutic hypothermia for 24 hours and recovered completely without neurological impairment after eight days of incident. Conclusion: Therapeutic hypothermia in eligible cardiac arrest patients is an important component of the post-cardiac arrest care in the AHA chain of survival. The AHA chain of survival is a chain of five interdependent links for cardiac arrest and comprises early recognition, early CPR, early defibrillation, early advanced cardiac life support and post-cardiac arrest care. It has substantial benefits on patient outcome. The ease of administration and positive clinical outcome should encourage other medical professionals to avail this modality.

Time to Rethink Sepsis as a Contraindication to Post Cardiac Arrest Therapeutic Hypothermia? A Retrospective Analysis of Outcomes of PCATH With and Without Ensuing Sepsis

Time to Rethink Sepsis as a Contraindication to Post Cardiac Arrest Therapeutic Hypothermia? A Retrospective Analysis of Outcomes of PCATH With and Without Ensuing Sepsis

NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest

IntroductionPrognostication of cardiac arrest survivors is challenging since therapeutic hypothermia (TH) has been introduced. We evaluated serum biomarkers and motor response. MethodsThis was a retrospective data analysis including patients in the years 2007–2012. Blood was drawn and a neurological examination was performed on admission and every morning. Outcomes were evaluated 6 months after discharge and dichotomized into good (cerebral performance category (CPC)=1 or 2) and poor (CPC=3, 4 or 5). Results123 patients (79.7% male, 63±14 years) received TH; 50% had a good outcome. On admission, S-100B (P=0.004) was significantly associated with the outcome, as well as neuron-specific enolase (NSE; P=0.020) and S-100B (P=0.004) on day 1 after admission. NSE on day 2, NSE progression from day 1 to 2 and motor response on day 3 also predicted the outcome (all P<0.001).NSE>33μgl−1 only predicted a poor outcome with a specificity of 76%. An absent motor response on day 3 was the most sensitive marker (94%). NSE>41.1μgl−1 combined with S-100B>0.461μgl−1 on day 1 was the most specific marker (96%). ConclusionAlthough NSE and S-100B levels are associated with the outcome, the use of previously described cut-off values was insufficiently predictive of neurologic outcome. Caution should be exercised in the use of these tests to provide neuroprognostication.

Abstract 221: The Use of Invasive Hemodynamic Monitoring in Evaluating Resuscitative End Points in Post--Cardiac Arrest Therapeutic Hypothermia (COMICA Study Group)

Introduction: Patients who suffer from post-cardiac arrest syndrome (PCAS) often exhibit an inflammatory response similar to a sepsis syndrome. Invasive hemodynamic monitoring of resuscitative endpoints has been proven to impart better mortality outcomes in sepsis and has been recommended for goal-directed management of PCAS patients. Hypothesis: Centers engaged in aggressive post-cardiac arrest care will utilize invasive hemodynamic monitoring to ascertain adequacy of resuscitative endpoints including central venous pressure (CVP) and central venous oxygen saturation (ScvO 2 ). Methods: This study is a collaboration of 4 centers with aggressive PCAS and therapeutic hypothermia protocols. It is a secondary analysis from prospectively collected data of out-of-hospital cardiac arrest patients who underwent TH. The primary objective was to determine the use of invasive hemodynamic monitoring in the care of PCAS patients undergoing TH. The secondary objective was to determine if either CVP or ScvO 2 were associated with neurologic outcome measured as cerebral performance category (CPC), dichotomized into “good” (1 or 2) or “poor” (3, 4 or 5). Study variables were abstracted at baseline, 12, 24, 36 and 48 hrs. Results: A total of 111 patients were enrolled. Patients were 61 ± 16.8 yrs, 59.5% male, and had an initial rhythm of VF/VT in 50.5% of cases. At baseline, 11% (12/111) of patients had a CVP recorded and 3.6% (4/111) has ScvO 2 measured. During the middle 24 hrs, an average of 65% (72) of patients had CVP recordings and 21.6% (24) of patients had ScvO 2 recorded. ScvO 2 values were not different between patients with good versus poor neurologic outcome. Lower CVP measurement was associated with better neurologic outcome. Conclusion: ScvO 2 was infrequently utilized in this cohort of PCAS patients undergoing TH. CVP was utilized at higher rates, and lower CVP recordings were correlated with better neurologic outcome.

Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest

ObjectiveTherapeutic hypothermia, also known as targeted temperature management (TTM), improves clinical outcomes in patients resuscitated from cardiac arrest. Hyperthermia after discontinuation of active temperature management (“rebound pyrexia”) has been observed, but its incidence and association with clinical outcomes is poorly described. We hypothesized that rebound pyrexia is common after rewarming in post-arrest patients and is associated with poor neurologic outcomes. MethodsRetrospective multicenter US clinical registry study of post-cardiac arrest patients treated with TTM at 11 hospitals between 5/2005 and 10/2011. We assessed the incidence of rebound pyrexia (defined as temperature >38°C) in post-arrest patients treated with TTM and subsequent clinical outcomes of survival to discharge and “good” neurologic outcome at discharge, defined as cerebral performance category (CPC) 1–2. ResultsIn this cohort of 236 post-arrest patients treated with TTM, mean age was 58.1±15.7y and 106/236 (45%) were female. Of patients who survived at least 24h after TTM discontinuation (n=167), post-rewarming pyrexia occurred in 69/167 (41%), with a median maximum temperature of 38.7 (IQR 38.3–38.9). There were no significant differences between patients experiencing any pyrexia and those without pyrexia regarding either survival to discharge (37/69 (54%) v 51/98 (52%), p=0.88) or good neurologic outcomes (26/37 (70%) v 42/51 (82%), p=0.21). We compared patients with marked pyrexia (greater than the median pyrexia of 38.7°C) versus those who experienced no pyrexia or milder pyrexia (below the median) and found that survival to discharge was not statistically significant (40% v 56% p=0.16). However, marked pyrexia was associated with a significantly lower proportion of CPC 1–2 survivors (58% v 80% p=0.04). ConclusionsRebound pyrexia occurred in 41% of TTM-treated post-arrest patients, and was not associated with lower survival to discharge or worsened neurologic outcomes. However, among patients with pyrexia, higher maximum temperature (>38.7°C) was associated with worse neurologic outcomes among survivors to hospital discharge.