Targeted Temperature Management for Out-of-Hospital Cardiac Arrest Survivors.

Targeted temperature management (TTM), specifically therapeutic hypothermia, has been proposed to provide neuroprotective and mortality benefits for out-of-hospital cardiac arrest (OHCA) survivors. This proposition was based on small-scale trials from the early 2000s, leading to its incorporation into various international guidelines. The proposed neuroprotective mechanisms include reducing cerebral metabolic rate, stabilizing the blood-brain barrier, reducing the release of excitatory neurotransmitters, and suppressing apoptotic pathways. However, these early trials have been criticized for their high risk of bias and lack of standardized protocols. Recent evidence from more rigorously controlled randomized trials indicates no significant association between hypothermia and improved neurological outcomes or survival rates. This review explores the latest clinical evidence on TTM for OHCA patients, discussing the pathophysiology, evaluating the effectiveness of hypothermia through various clinical trials, and providing recommendations for future research and clinical practice.

Neonatal encephalopathy due to suspected hypoxic ischemic encephalopathy: pathophysiology, current, and emerging treatments.

BACKGROUND: Neonatal encephalopathy (NE) due to suspected hypoxic-ischemic encephalopathy (HIE), referred to as NESHIE, is a clinical diagnosis in late preterm and term newborns. It occurs as a result of impaired cerebral blood flow and oxygen delivery during the peripartum period and is used until other causes of NE have been discounted and HIE is confirmed. Therapeutic hypothermia (TH) is the only evidence-based and clinically approved treatment modality for HIE. However, the limited efficacy and uncertain benefits of TH in some low- to middle-income countries (LMICs) and the associated need for intensive monitoring have prompted investigations into more accessible and effective stand-alone or additive treatment options. DATA SOURCES: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE based on literatures from Pubmed and other online sources of published data. RESULTS: The underlining mechanisms of neurotoxic effect, current clinically approved treatment, various categories of emerging treatments and clinical trials for NE are summarized in this review. Melatonin, caffeine citrate, autologous cord blood stem cells, Epoetin alfa and Allopurinal are being tested as potential neuroprotective agents currently. CONCLUSION: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE. Neuroprotective agents are currently only being investigated in high- and middle-income settings. Results from these trials will need to be interpreted and validated in LMIC settings. The focus of future research should therefore be on the development of inexpensive, accessible monotherapies and should include LMICs, where the highest burden of NESHIE exists.

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.

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.

Escenarios para el diagnóstico de encefalopatía hipóxico isquémica e inicio de tratamiento con hipotermia controlada en recién nacidos con asfixia perinatal / Scenarios for the diagnosis of hypoxic-ischemic encephalopathy and initiation of therapeutic hypothermia treatment in newborns with perinatal asphyxia / Cenários para o diagnóstico da encefalopatia hipóxico-isquemia e início de tratamento de hipotermia terapêutica a recém-nascidos com asfixia perinatal

La hipoxia isquemia perinatal y su complicación más temida, la encefalopatía hipóxica isquémica, continúa siendo uno de los principales motivos de ingreso a las unidades de cuidados neonatales. En la actualidad la hipotermia controlada es el tratamiento recomendado para los pacientes con encefalopatía moderada a severa, dado su carácter de neuroprotección ante la injuria cerebral hipóxico isquémica. Si bien los criterios de inclusión en esta terapia han sido bien establecidos, aún hay dificultades tanto en la identificación precoz de aquellos que pueden verse beneficiados, como en la toma de decisiones ante situaciones de controversia entre la evidencia disponible y la que se está gestando en estudios en curso. Este artículo pretende aportar herramientas al clínico para abordar diferentes escenarios que surgen de la práctica diaria.

Perinatal hypoxic ischemia and its most feared complication, hypoxic ischemic encephalopathy, remain one of the main reasons for admission to neonatal care. Controlled hypothermia is currently the recommended treatment for patients with moderate to severe encephalopathy, given its neuroprotective nature against hypoxic-ischemic brain injury. Although the inclusion criteria for this therapy have been well established, there are still difficulties both in the early identification of those who may benefit, and in making decisions regarding situations of controversy between the available evidence and that being developing in ongoing studies. This paper aims at providing tools so that clinicians can address different scenarios that arise during their daily practice.

A hipóxia isquêmica perinatal e sua complicação mais temida, a encefalopatia hipóxico-isquêmica, continuam sendo um dos principais motivos de internação em unidades de cuidados neonatais. A hipotermia controlada é atualmente o tratamento recomendado para pacientes com encefalopatia moderada a grave, dada a sua natureza neuroprotetora contra lesão cerebral hipóxico-isquêmica. Embora os critérios de inclusão dessa terapia estejam bem estabelecidos, ainda há dificuldades tanto na identificação precoce daqueles que podem se beneficiar, quanto na tomada de decisões em situações de controvérsia entre as evidências disponíveis e aquelas que estão se desenvolvendo em estudos em andamento. Este paper tem como objetivo fornecer ferramentas aos clínicos para abordar diferentes cenários que surgem da prática diária.

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.