Temperature management in acute brain injury: A narrative review.

Temperature management has been used in patients with acute brain injury resulting from different conditions, such as post-cardiac arrest hypoxic-ischaemic insult, acute ischaemic stroke, and severe traumatic brain injury. However, current evidence offers inconsistent and often contradictory results regarding the clinical benefit of this therapeutic strategy on mortality and functional outcomes. Current guidelines have focused mainly on active prevention and treatment of fever, while therapeutic hypothermia (TH) has fallen into disuse, although doubts persist as to its effectiveness according to the method of application and appropriate patient selection. This narrative review presents the most relevant clinical evidence on the effects of TH in patients with acute neurological damage, and the pathophysiological concepts supporting its use.

Cardiogenic Shock Intravascular Cooling Trial (CHILL-SHOCK).

BACKGROUND: Cardiogenic shock (CS) is complicated by high mortality rates. Targeted temperature control (TTC) has been proposed as an adjunct therapy in CS. This study aims to examine the safety of TTC in patients presenting with CS. METHODS AND RESULTS: In this open-label, randomized controlled pilot trial, 20 patients with hemodynamic criteria for CS were assigned to standard of care plus TTC vs standard of care alone. The primary outcome was a composite safety outcome, including well-described complications of TTC. Secondary outcomes included mortality at 90 days, invasive hemodynamic and echocardiographic parameters, electrocardiographic measurements, and inotrope dosing. There were no significant differences in the composite analysis of prespecified safety outcomes (3 events in the TTC group vs 0 events in the control group; P = 0.24). Patients randomized to TTC demonstrated a statistically significant increase in cardiac index and cardiac power index compared to the control group at 48-96 hours after randomization (3.6 [3.1, 3.9] L/min/m2 vs 2.6 [2.5, 3.15] L/min/m2; P = 0.029 and 0.61 [0.55, 0.7] W/m2 vs 0.53 [0.435, 0.565] W/m2; P = 0.029, respectively). CONCLUSION: TTC may be a safe adjunct therapy for patients presenting with CS and may yield improvement in specific hemodynamic parameters.

Short-term neurological injury in newborns infants with overcooling in passive hypothermia and transferred to reference hospital in Colombia.

AIM: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short-term neurological injury. METHODS: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both. RESULTS: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1-77.3) were associated with neurological injury before discharge from the unit. CONCLUSION: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia.

The use of induced hypothermia in extracorporeal membrane oxygenation: A narrative review.

Despite venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) being increasingly used in patients with severe acute respiratory disease syndrome, severe cardiogenic shock, and refractory cardiac arrest, mortality rates still remain high mainly because of the severity of the underlying disease and the numerous complications associated with initiation of ECMO. Induced hypothermia might minimize several pathological pathways present in patients requiring ECMO; even though numerous studies conducted in the experimental setting have reported promising results, there are currently no recommendations suggesting the routine use of this therapy in patients requiring ECMO. In this review, we summarized the existing evidence on the use of induced hypothermia in patients requiring ECMO. Induced hypothermia was a feasible and relatively safe intervention in this setting; however, the effects on clinical outcomes remain uncertain. Whether controlled normothermia has an impact on these patients compared with no temperature control remains unknown. Further randomized controlled trials are required to better understand the role and impact of such therapy in patients requiring ECMO according to the underlying disease.

The Association Between Induction Rate and Neurologic Outcome in Patients Undergoing Targeted Temperature Management at 33°C.

To determine the association between the induction rate and 6-month neurologic outcomes in out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management (TTM). This retrospective observational study analyzed data prospectively collected from adult comatose OHCA survivors treated with TTM at the Chonnam National University Hospital in Gwangju, Korea, between October 2015 and December 2020. We measured the core body temperature (BT) through an esophageal probe and recorded it every 5 minutes throughout TTM. Induction time was defined as the elapsed time between the initiation of TTM and the achievement of target BT of 33°C. We calculated the induction rate as the change of BT divided by induction time. The primary outcome was a poor 6-month neurologic outcome, defined as cerebral performance category 3-5. Of the OHCA survivors, 218 patients were included, and 137 (62.8%) patients had a poor neurologic outcome. Patients with a poor neurologic outcome had lower BT at the initiation of TTM, shorter induction time, and higher induction rate than those with good neurologic outcomes. After adjusting for confounders, induction time (odds ratio [OR] 0.995; 95% confidence interval [CI], 0.992-0.999) and induction rate (OR 2.362; 95% CI, 1.178-4.734) were independently associated with poor neurologic outcome. BT at TTM initiation was not associated with a poor neurologic outcome. Induction rate was independently associated with a poor neurologic outcome in OHCA survivors who underwent TTM at 33°C.

Differential Effect of Targeted Temperature Management Between 32 °C and 36 °C Following Cardiac Arrest According to Initial Severity of Illness: Insights From Two International Data Sets.

BACKGROUND: Recent guidelines have emphasized actively avoiding fever to improve outcomes in patients who are comatose following resuscitation from cardiac arrest (ie, out-of-hospital cardiac arrest). However, whether targeted temperature management between 32 °C and 36 °C (TTM32-36) can improve neurologic outcome in some patients remains debated. RESEARCH QUESTION: Is there an association between the use of TTM32-36 and outcome according to severity assessed at ICU admission using a previously derived risk score? STUDY DESIGN AND METHODS: Data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (France) between May 2011 and December 2017 and in the Resuscitation Outcomes Consortium Continuous Chest Compressions (ROC-CCC) trial (United States and Canada) between June 2011 and May 2015 were used for this study. Severity at ICU admission was assessed through a modified version of the Cardiac Arrest Hospital Prognosis (mCAHP) score, divided into tertiles of severity. The study explored associations between TTM32-36 and favorable neurologic status at hospital discharge by using multiple logistic regression as well as in tertiles of severity for each data set. RESULTS: A total of 2,723 patients were analyzed in the SDEC data set and 4,202 patients in the ROC-CCC data set. A favorable neurologic status at hospital discharge occurred in 728 (27%) patients in the French data set and in 1,239 (29%) patients in the North American data set. Among the French data set, TTM32-36 was independently associated with better neurologic outcome in the tertile of patients with low (adjusted OR, 1.63; 95% CI, 1.15-2.30; P = .006) and high (adjusted OR, 1.94; 95% CI, 1.06-3.54; P = .030) severity according to mCAHP at ICU admission. Similar results were observed in the North American data set (adjusted ORs of 1.36 [95% CI, 1.05-1.75; P = .020] and 2.42 [95% CI, 1.38-4.24; P = .002], respectively). No association was observed between TTM32-36 and outcome in the moderate groups of the two data sets. INTERPRETATION: TTM32-36 was significantly associated with a better outcome in patients with low and high severity at ICU admission assessed according to the mCAHP score. Further studies are needed to evaluate individualized temperature control following out-of-hospital cardiac arrest.

Target Temperature Management Following Pediatric Cardiac Arrest: A Systematic Review and Network Meta-Analysis to Compare the Effectiveness of the Length of Therapeutic Hypothermia.

We aimed to compare the efficacy of therapeutic hypothermia for 24, 48, and 72 h, and normothermia following pediatric cardiac arrest. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via Ovid, World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov. from their inception to December 2021. We included randomized controlled trials and observational studies evaluating target temperature management (TTM) in children aged < 18 years with the return of spontaneous circulation (ROSC) after cardiac arrest. We compared four intervention groups (normothermia, therapeutic hypothermia for 24 h (TTM 24h), therapeutic hypothermia for 48 h (TTM 48h), and therapeutic hypothermia for 72 h (TTM 72h)) using network meta-analysis. The outcomes were survival and favorable neurological outcome at 6 months or more. Seven studies involving 1008 patients and four studies involving 684 patients were included in the quantitative synthesis of survival and neurological outcome, respectively. TTM for 72 h was associated with a higher survival rate, compared to normothermia (RR 1.75 (95% CI 1.27-2.40)) (very low certainty), TTM 24h (RR 1.53 (95% CI 1.06-2.19)) (low certainty), and TTM 48h (RR 1.54 (95% CI 1.06-2.22)) (very low certainty). TTM for 72 h was also associated with favorable neurological outcomes compared with normothermia (RR 9.36 (95% CI 2.04-42.91)), or TTM 48h (RR 8.15 (95% CI 1.6-40.59)) (all very low certainty). TTM for 24 h was associated with favorable neurological outcome, compared with normothermia (RR 8.02 (95% CI 1.28-50.50)) (very low certainty). In the ranking analysis, the hierarchies for efficacy for survival and favorable neurological outcome were TTM 72h > TTM 48h > TTM 24h > normothermia. Although prolonged therapeutic hypothermia might be effective in pediatric patients with ROSC after cardiac arrest, the evidence to support this result is only weak to very weak. There is no conclusive evidence regarding the effectiveness and length of therapeutic hypothermia and high-quality RCRs comparing long-length therapeutic hypothermia to short-length hypothermia and normothermia are needed.

Targeted Temperature Management After Cardiac Arrest: A Systematic Review.

Targeted temperature management (TTM) has been the cornerstone of post-cardiac arrest care, but even after therapy, neurological outcomes remain poor. We performed a systematic review to evaluate the influence of TTM in post-cardiac arrest treatment, its effect on the neurological outcome, survival, and the adverse events associated with it. We also aimed to examine any difference between the effect of therapy at various intensities and durations on the prognosis of the patient. A search of two databases was done to find relevant studies, followed by a thorough screening in which the inclusion and exclusion criteria were applied, and a quality appraisal of clinical trials was done. In this systematic review, six randomized clinical trials with a total of 3870 participants were examined. Of these, 2,767 participants were treated with targeted hypothermia to varying degrees (between 31 and 36 degrees Celsius), 931 participants were treated with targeted normothermia (36.5 to 37.5 degrees Celsius), and 172 participants were treated with only normothermia (without any active cooling or interventions). It was concluded that TTM at a lower temperature did not have any benefit regarding the neurological outcome and mortality over targeted normothermia but was superior to no temperature management. TTM was also found to have significantly more negative effects when the intensity or duration was increased.

Adición de melatonina a terapia con hipotermia para encefalopatía hipóxico-isquémica neonatal / Addition of melatonin to hypothermia therapy for neonatal hypoxic-ischemic encephalopathy

Introducción La encefalopatía hipóxico-isquémica neonatal es una patología caracterizada por una disfunción neurológica aguda, de severidad variable, causada por un episodio asfíctico perinatal. Se presenta en uno a seis de cada 1000 recién nacidos de término, asociándose a una alta morbimortalidad neonatal y a desenlaces neurológicos adversos. El uso de hipotermia es considerado como la terapia estándar para esta condición. Sin embargo, debido a su limitada eficacia clínica, se han propuesto diferentes opciones terapéuticas adyuvantes, incluyendo el uso de fármacos como la melatonina. Existe controversia sobre si la terapia combinada con melatonina es superior a la monoterapia con hipotermia. Métodos Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método Grading of Recommendations Assessment, Development and Evaluation, GRADE Resultados Identificamos dos revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Se incluyeron los dos ensayos aleatorizados en el análisis del presente trabajo. Conclusiones No es posible establecer con claridad si la adición de melatonina disminuye la mortalidad o la probabilidad de presentar alteraciones reflejadas en la resonancia magnética cerebral, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja. Por otro lado, adicionar melatonina a la terapia con hipotermia, comparado con la monoterapia con hipotermia, podría aumentar la probabilidad de que el examen neurológico sea normal a los seis meses, y que la cognición sea normal a los 18 meses. Finalmente, la adición de melatonina a la terapia con hipotermia probablemente disminuya la probabilidad de presentar convulsiones.

Introduction Neonatal hypoxic-ischemic encephalopathy is caused by perinatal asphyxia, resulting in an acute neurological dysfunction of variable severity. It occurs in one to six of every 1000 full-term newborns and is associated with high neonatal morbimortality and adverse neurological outcomes. The use of hypothermia is considered the standard therapy for this condition. However, different adjuvant therapeutic options have been proposed due to limited clinical efficacy, including drugs like melatonin. There is controversy about whether combined therapy with melatonin is superior to monotherapy with hypothermia. Methods We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, and Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of the findings table using the GRADE approach. Results We identified two systematic reviews that included two primary studies, both randomized trials. The two randomized trials were included in the analysis of the present work. Conclusion It is not possible to establish whether the addition of melatonin decreases mortality or the probability of alterations in brain magnetic resonance imaging because the certainty of the existing evidence has been assessed as very low. On the other hand, the addition of melatonin to hypothermia therapy, compared to hypothermia monotherapy, may increase the probability of normal neurological examination at six months and the probability of normal cognition at 18 months. Finally, adding melatonin to hypothermia therapy likely reduces the probability of seizures.

Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management.

Evolution toward brain death (BD) in out-of-hospital cardiac arrest patients with targeted temperature management (TTM) provides opportunities for organ donation. However, knowledge regarding BD in these patients is limited. We retrospectively analyzed the TTM registry of one hospital where life-sustaining therapy was not withdrawn. In-hospital death patients were categorized into BD and non-BD groups. We explored the process of evolution toward BD and its predictors by comparing the serial measurements of clinical variables and the results of various prognostic tests between the two groups. Of the 121 patients who died before hospital discharge, 19 patients (15.7%) developed BD at a median of 6 (interquartile range, 5.0-7.0) days after cardiac arrest. Four patients with pupillary light reflexes at 48 h eventually developed BD. The area under the curves of the gray-to-white matter ratio (GWR) on early brain computed tomography images and the level of S100 calcium-binding protein B (S100B) at 72 h were 0.67 (95% CI, 0.55-0.77) and 0.70 (95% CI, 0.55-0.83), respectively. In conclusion, approximately one-sixth of all in-hospital deaths were diagnosed with BD at a median of 6 days after cardiac arrest. The use of GWR and serial S100B measurements may help to screen potential BD.

Clinically induced hypothermia with cardiopulmonary support in a high-risk patient undergoing carotid endarterectomy.

Contralateral carotid occlusion increases the risk of stroke by hypoperfusion in patients undergoing carotid surgery. We present the case of a high-risk patient with crescendo cerebral ischemic events, for whom clinically induced hypothermia controlled by cardiopulmonary bypass was applied as a protective measure during carotid endarterectomy.

Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials. METHODS: We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32-34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects. RELEVANCE FOR PATIENTS: Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67-1.16; n = 3243; I2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93-1.84; n = 3091; I2 = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20-1.71; n = 3029; I2 = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98-1.31; n = 3056; I2 = 22%). Therefore, targeted hypothermia with a target temperature of 32-34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.

Relationship between cooling time and neurological outcomes in targeted temperature management.

OBJECTIVES: The relationship between cooling time (CT) variables and neurological outcomes is controversial. We evaluated the relationship between CT and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). METHODS: We conducted a multicenter, prospective, and registry-based study of OHCA survivors treated with TTM. CT was defined as the time from restoration of spontaneous circulation to achievement of the target temperature. The primary outcome was a favorable neurological outcome at 6 months. Multilevel logistic regression analysis was performed to test the relationship between CT and the primary outcome. RESULTS: Overall, the favorable neurological outcome rates at 6 months were 29.8% in 937 patients. When CT was stratified into categories of 0-3, 3.1-6, 6.1-9, 9.1-12, and >12 h, according to 3-h intervals, the primary outcome rates were 8.2%, 22.7%, 35.5%, 44.7%, and 44.5%, respectively (p < 0.001). Significant differences were not found in multilevel logistic regression analysis; the adjusted odds ratios (95% confidence interval) of each category for the primary outcome compared to the 0-3-h group were 0.81 (0.32 to 2.04), 0.77 (0.30 to 2.01), 1.26 (0.43 to 3.68), and 1.06 (0.37 to 3.06). CONCLUSIONS: We did not find a relationship between CT and neurological outcomes at 6 months.

Comparison of intracranial pressure changes in out-of-hospital cardiac arrest patients with and without malignant blood-brain barrier disruption.

OBJECTIVE: In the present study, intracranial pressure (ICP) changes were investigated in out-ofhospital cardiac arrest (OHCA) patients with and without malignant blood-brain barrier (BBB) disruption who underwent target temperature management. METHODS: This prospective, single-center, observational study was conducted from June 2019 to December 2021. ICP and albumin quotient values were measured on days 1, 2, 3, and 4 of hospitalization. Malignant BBB disruption was defined as the sum of scores for the degree of BBB disruption ≥9 on days 1 to 4. RESULTS: ICP in OHCA patients without malignant BBB disruption on days 1, 2, 3, and 4 of hospitalization was 9.58±0.53, 12.32±0.65, 14.39±0.76, and 13.88±0.87 mmHg, respectively, and in OHCA patients with malignant BBB disruption 13.65±0.74, 15.72±0.67, 16.10±0.92, and 15.22±0.87 mmHg, respectively (P<0.001, P<0.001, P=0.150, and P=0.280, respectively). The P-values of changes in ICP between days 1 and 2, days 2 and 3, and days 3 and 4 of hospitalization in OHCA patients without malignant BBB disruption were P<0.001, P=0.001, and P=0.540, respectively, and in OHCA patients with malignant BBB disruption were P=0.002, P=0.550, and P=0.100, respectively. CONCLUSION: Among OHCA patients treated with target temperature management, ICP was higher on days 1 and 2 of hospitalization and an increase in ICP occurred earlier with malignant BBB disruption than without malignant BBB disruption.

Water Temperature Variability Is Associated with Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Survivors Who Underwent Targeted Temperature Management at 33°C.

We examined the association between variability in body temperature (BT) and water temperature (WT) during the maintenance period of targeted temperature management (TTM) and neurologic outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Adult (≥18 years), comatose OHCA survivors who underwent TTM at 33°C between October 2015 and December 2019 were included. We collected data on BT and WT recorded every minute during the TTM maintenance period. Temperature variability was measured as the standard deviation of BT and WT during the 33°C maintenance period. The primary outcome was a poor neurologic outcome, defined as a cerebral performance category scale 3-5 at 6 months. Of the 154 included patients, 96 (62.3%) had poor outcomes. The BT variability in the poor outcome group was lower than that in the good outcome group (0.16°C [0.13-0.27°C] vs. 0.13°C [0.11-0.18°C]). In addition, the WT variability during the maintenance period in the poor outcome group was lower than that in the good outcome group (2.24°C [1.80-3.96°C] vs. 1.77°C [1.26-2.32°C]). In the multivariate analysis, WT variability (odds ratio 0.508; 95% confidence interval, 0.295-0.874; p = 0.014) was independently associated with poor neurologic outcome. BT variability and cooling beyond 33.0°C ± 1.0°C were not associated with poor neurologic outcomes. WT variability during the maintenance period was independently associated with neurologic outcomes in OHCA survivors who underwent TTM at 33°C. In addition, overcooling or undercooling during the maintenance period was not associated with neurologic outcomes.

Pre Versus Post Implementation of a Pharmacologic Antishivering Protocol During Targeted Temperature Management Following Cardiac Arrest.

BACKGROUND: Targeted temperature management (TTM) is endorsed by various guidelines to improve neurologic outcomes following cardiac arrest. Shivering, a consequence of hypothermia, can counteract the benefits of TTM. Despite its frequent occurrence, consensus guidelines provide minimal guidance on the management of shivering. The purpose of this study was to evaluate the impact of a pharmacologic antishivering protocol in patients undergoing TTM following cardiac arrest on the incidence of shivering. METHODS: A retrospective observational cohort study at a large academic medical center of adult patients who underwent TTM targeting 33 °C following out-of-hospital (OHCA) or in-hospital cardiac arrest (IHCA) was conducted between January 2013 and January 2019. Patients were included in the preprotocol group if they received TTM prior to the initiation of a pharmacologic antishivering protocol in 2015. The primary outcome was incidence of shivering between pre- and postprotocol patients. Secondary outcomes included time from arrest (IHCA) or admission to the hospital (OHCA) to goal body temperature, total time spent at goal body temperature, and percentage of patients alive at discharge. All pharmacologic agents listed as part of the antishivering protocol were recorded. RESULTS: Fifty-one patients were included in the preprotocol group, and 80 patients were included in the postprotocol group. There were no significant differences in baseline characteristics between the groups, including percentage of patients experiencing OHCA (75% vs. 63%, p = 0.15) and time from arrest to return of spontaneous circulation (17.5 vs. 17.9 min, p = 0.96). Incidence of patients with shivering was significantly reduced in the postprotocol group (57% vs. 39%, p = 0.03). Time from arrest (IHCA) or admission to the hospital (OHCA) to goal body temperature was similar in both groups (5.1 vs. 5.3 h, p = 0.57), in addition to total time spent at goal body temperature (17.7 vs. 18 h, p = 0.93). The percentage of patients alive at discharge was significantly improved in the postprotocol group (35% vs. 55%, p = 0.02). Patients in the postprotocol group received significantly more buspirone (4% vs. 73%, p < 0.01), meperidine (8% vs. 34%, p < 0.01), and acetaminophen (12% vs. 65%, p < 0.01) as part of the pharmacologic antishivering protocol. Use of neuromuscular blockade significantly decreased post protocol (19% vs. 6%, p = 0.02). CONCLUSIONS: In patients undergoing TTM following cardiac arrest, the implementation of a pharmacologic antishivering protocol reduced the incidence of shivering and the use neuromuscular blocking agents. Prospective data are needed to validate the results and further evaluate the safety and efficacy of an antishivering protocol on clinical outcomes.

Neuroprotective Agents for Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) remains a significant source of long-term neurodevelopmental impairment despite overall improvements in survival without disability in neonates who undergo therapeutic hypothermia. Each phase in the evolution of hypoxic-ischemic injury presents potential pharmacologic targets for neuroprotective agents. Melatonin is a promising emerging therapy for early phases of ischemic injury, but utility is currently limited by the lack of pharmaceutical-grade products. Magnesium has been extensively studied for its neuroprotective effects in the preterm population. Studies in neonates with HIE have produced mixed outcomes. Erythropoietin use in HIE with or without therapeutic hypothermia appears to be safe and may provide additional benefit. Dexmedetomidine, N-acetylcysteine, xenon, and topiramate all have promising animal data, but need additional human trials to elucidate what role they may play in HIE. Frequent review of existing literature is required to ensure provision of evidence-based pharmacologic agents for neuroprotection following HIE.

Women receive less targeted temperature management than men following out-of-hospital cardiac arrest due to early care limitations - A study from the CARES Investigators.

BACKGROUND: Women experience worse neurological outcomes following out-of-hospital cardiac arrest (OHCA). It is unknown whether sex disparities exist in the use of targeted temperature management (TTM), a standard of care treatment to improve neurological outcomes. METHODS: We performed a retrospective study of prospectively collected patients who survived to hospital admission following OHCA from the Cardiac Arrest Registry to Enhance Survival from 2013 through 2019. We compared receipt of TTM by sex in a mixed-effects model adjusted for patient, arrest, neighborhood, and hospital factors, with the admitting hospital modeled as a random intercept. RESULTS: Among 123,419 patients, women had lower rates of shockable rhythms (24.4 % vs. 39.2%, P < .001) and lower rates of presumed cardiac aetiologies for arrest (74.3% vs. 81.1%, P < .001). Despite receiving a similar rate of TTM in the field (12.1% vs. 12.6%, P = .02), women received less TTM than men upon admission to the hospital (41.6% vs. 46.4%, P < .001). In an adjusted mixed-effects model, women were less likely than men to receive TTM (Odds Ratio 0.91, 95% Confidence Interval 0.89 to 0.94). Among the 27,729 patients with data indicating the reason for not using TTM, a higher percentage of women did not receive TTM due to Do-Not-Resuscitate orders/family requests (15.1% vs. 11.4%, p < .001) and non-shockable rhythms (11.1% vs. 8.4%, p < .001). CONCLUSIONS: We found that women received less TTM than men, likely due to early care limitations and a preponderance of non-shockable rhythms.

The Effect of Therapeutic Hypothermia after Cardiac Arrest on the Neurological Outcome and Survival-A Systematic Review of RCTs Published between 2016 and 2020.

Therapeutic hypothermia is a treatment used for patients who have suffered cardiorespiratory arrest and remain conscious after the recovery of spontaneous circulation. However, its effectiveness is controversial. The objective of this systematic review is to summarize the scientific evidence available about the effect of therapeutic hypothermia on neurological status and survival in this type of patients. METHODOLOGY: A primary search in CINAHL, CUIDEN, Pubmed, Web of Science, and Scopus databases was carried out. Randomized clinical trials (RCT) published from 2016 to 2020 were selected. RESULTS: 17 studies were selected for inclusion and most relevant data were extracted. Methodological quality was assessed by the RoB tool. CONCLUSIONS: Although therapeutic hypothermia is a safe technique with few adverse and manageable effects, it has not shown to improve survival rate and neurological status of adult nor pediatric patients. It is possible that its positive effect on neuroprotection could be achieved only by preventing hyperthermia although further investigation is needed.