• Activated protein kinase C
• Endovascular therapy
• Human urinary kallidinogenase
• Neuroprotective
• Stem cell therapy
• Stroke
• Vagus nerve stimulation

• Humans
• Ischemic Stroke/therapy
• Animals
• Hypothermia, Induced/methods
• Thrombolytic Therapy/methods
• Neuroprotective Agents/therapeutic use
• Endovascular Procedures/methods
• Fibrinolytic Agents/therapeutic use
• Vagus Nerve Stimulation/methods

• CCL23
• Cardiac arrest
• Inflammation
• Mouse model of cardiac arrest and resuscitation
• Neutrophils

• Humans
• Mice
• Animals
• Heart Arrest/complications
• Chemokines
• Chemokines, CC

• R01 HL139887 NHLBI NIH HHS
• U54 GM115516 NIGMS NIH HHS
• U01 HL100398 NHLBI NIH HHS
• R01 HL136560 NHLBI NIH HHS
• P20 GM139745 NIGMS NIH HHS
• R01 HL173118 NHLBI NIH HHS
• P30 GM106391 NIGMS NIH HHS

• esophageal cooling
• esophageal device
• evaporative cooling
• therapeutic hypothermia
• transesophageal air
• transesophageal cooling

• Cooling methods
• neuroprotection
• selective brain cooling
• selective brain hypothermia
• therapeutic hypothermia

• Blood pressure
• Carbon dioxide
• Cardiac arrest
• Glucose
• Oxygen
• Temperature

Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA.

We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality.

Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75–0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62–1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs.

Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).

The online version of this article (10.1186/s13054-019-2567-6) contains supplementary material, which is available to authorized users.

• Endovascular
• Meta-analysis
• Methods
• Neurological outcome
• Surface cooling
• Survival
• Targeted temperature management

Patients resuscitated from cardiac arrest (CA) have highly variable neurological, circulatory, and systemic ischemia‐reperfusion injuries. After the initial hypoxic‐ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors.

After informed consent, we collected blood samples at intervals over a week after resuscitation from CA. We examined the expression of CD39 and CD73 (alias 5′‐nucleotidase), production of tumor necrosis factor‐α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD73‐expressing lymphocytes correlated with survival after CA. Incubation of immune cells, obtained from post‐CA subjects, with AMP, a substrate for CD73, resulted in inhibition of tumor necrosis factor‐α production and generation of reactive oxygen species. This effect was blocked by adenosine 5′‐(α, β‐methylene) diphosphate, a specific inhibitor of CD73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP‐dependent activation of CD73 induces production of vascular endothelial growth factor.

CD73‐expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study.

• CD73
• cardiac arrest
• inflammation
• lymphocytes

• cooling device
• hypothermia
• target temperature management
• temperature control
• transnasal

• Animals
• Body Temperature Regulation
• Equipment Design
• Female
• Hypothermia, Induced/instrumentation
• Materials Testing
• Models, Animal
• Sus scrofa
• Time Factors
• Turbinates/physiology

• R44 HL108542 NHLBI NIH HHS

Out-of-hospital cardiac arrest (CA) remains a leading cause of sudden morbidity and mortality; however, outcomes have continued to improve in the era of targeted temperature management (TTM). In this review, we highlight the clinical use of TTM, and provide an updated summary of multimodality monitoring possible in a modern ICU. TTM is neuroprotective for survivors of CA by inhibiting multiple pathophysiologic processes caused by anoxic brain injury, with a final common pathway of neuronal death. Current guidelines recommend the use of TTM for out-of-hospital CA survivors who present with a shockable rhythm. Further studies are being completed to determine the optimal timing, depth and duration of hypothermia to optimize patient outcomes. Although a multidisciplinary approach is necessary in the CA population, neurologists and neurointensivists are central in selecting TTM candidates and guiding patient care and prognostic evaluation. Established prognostic tools include clinal exam, SSEP, EEG and MR imaging, while functional MRI and invasive monitoring is not validated to improve outcomes in CA or aid in prognosis. We recommend that an evidence-based TTM and prognostication algorithm be locally implemented, based on each institution's resources and limitations. Given the high incidence of CA and difficulty in predicting outcomes, further study is urgently needed to determine the utility of more recent multimodality devices and studies.

• EEG
• anoxic brain injury
• cardiac arrest
• multimodality monitoring
• prognosis
• targeted temperature management

• Cardiac arrest
• Feasibility
• Gastrointestinal endoscopy
• Oesophageal cooling
• Safety
• Therapeutic hypothermia

• Endovascular cooling
• Intracranial pressure
• Ischemic/hypoxic encephalopathy
• Neuroprotective therapy
• Surface cooling
• Targeted temperature management

Targeted temperature management is recommended after out-of-hospital cardiac arrest and may be achieved using a variety of cooling devices. This study was conducted to explore the performance and outcomes for intravascular versus surface devices for targeted temperature management after out-of-hospital cardiac arrest.

A retrospective analysis of data from the Targeted Temperature Management trial. N = 934. A total of 240 patients (26%) managed with intravascular versus 694 (74%) with surface devices. Devices were assessed for speed and precision during the induction, maintenance and rewarming phases in addition to adverse events. All-cause mortality, as well as a composite of poor neurological function or death, as evaluated by the Cerebral Performance Category and modified Rankin scale were analysed.

For patients managed at 33 °C there was no difference between intravascular and surface groups in the median time taken to achieve target temperature (210 [interquartile range (IQR) 180] minutes vs. 240 [IQR 180] minutes, p = 0.58), maximum rate of cooling (1.0 [0.7] vs. 1.0 [0.9] °C/hr, p = 0.44), the number of patients who reached target temperature (within 4 hours (65% vs. 60%, p = 0.30); or ever (100% vs. 97%, p = 0.47), or episodes of overcooling (8% vs. 34%, p = 0.15). In the maintenance phase, cumulative temperature deviation (median 3.2 [IQR 5.0] °C hr vs. 9.3 [IQR 8.0] °C hr, p = <0.001), number of patients ever out of range (57.0% vs. 91.5%, p = 0.006) and median time out of range (1 [IQR 4.0] hours vs. 8.0 [IQR 9.0] hours, p = <0.001) were all significantly greater in the surface group although there was no difference in the occurrence of pyrexia. Adverse events were not different between intravascular and surface groups. There was no statistically significant difference in mortality (intravascular 46.3% vs. surface 50.0%; p = 0.32), Cerebral Performance Category scale 3–5 (49.0% vs. 54.3%; p = 0.18) or modified Rankin scale 4–6 (49.0% vs. 53.0%; p = 0.48).

Intravascular and surface cooling was equally effective during induction of mild hypothermia. However, surface cooling was associated with less precision during the maintenance phase. There was no difference in adverse events, mortality or poor neurological outcomes between patients treated with intravascular and surface cooling devices.

TTM trial ClinicalTrials.gov number https://clinicaltrials.gov/ct2/show/NCT01020916NCT01020916; 25 November 2009

• Brain injuries
• Critical care
• Fever
• Hypothermia
• Induced
• Out-of-hospital cardiac arrest
• Shivering
• Temperature

Therapeutic hypothermia has emerged as a remarkably effective method of neuroprotection from ischemia and is being increasingly used in clinics. Accordingly, it is also a subject of considerable attention from a basic scientific research perspective. One of the fundamental problems, with which current studies are concerned, is the optimal method of inducing hypothermia. This review seeks to provide a broad theoretical framework for approaching this problem, and to discuss how a novel promising strategy of pharmacological modulation of the thermosensitive ion channels fits into this framework. Various physical, anatomical, physiological and molecular aspects of thermoregulation, which provide the foundation for this text, have been comprehensively reviewed and will not be discussed exhaustively here. Instead, the first part of the current review, which may be helpful for a broader readership outside of thermoregulation research, will build on this existing knowledge to outline possible opportunities and research directions aimed at controlling body temperature. The second part, aimed at a more specialist audience, will highlight the conceptual advantages and practical limitations of novel molecular agents targeting thermosensitive Transient Receptor Potential (TRP) channels in achieving this goal. Two particularly promising members of this channel family, namely TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1), will be discussed in greater detail.

• DMH, dorso-medial hypothalamus
• MPA, medial preoptic area of hypothalamus
• TRP, Transient Receptor Potential
• TRPA1, Transient Receptor Potential cation channel, subfamily A, member 1
• TRPM8, Transient Receptor Potential cation channel, subfamily M, member 8
• TRPV1, Transient Receptor Potential cation channel, subfamily V, member 1
• TRPV2, Transient Receptor Potential cation channel, subfamily V, member 2
• TRPV3, Transient Receptor Potential cation channel, subfamily V, member 3
• TRPV4, Transient Receptor Potential cation channel, subfamily V, member 4
• ThermoTRPs
• ThermoTRPs, Thermosensitive Transient Receptor Potential cation channels
• body temperature
• core temperature
• pharmacological hypothermia
• physical cooling
• rMR, rostral medullary raphe region
• therapeutic hypothermia
• thermopharmacology
• thermoregulation
• thermosensitive ion channels

Cardiac arrest, irrespective of its etiology, has a high mortality. This event is often associated with brain anoxia which frequently causes severe neurological damage and persistent vegetative state. Only one out of every six patients survives to discharge following in-hospital cardiac arrest, whereas only 2-9% of patients who experience out of hospital cardiac arrest survive to go home. Functional outcomes of survival are variable, but poor quality survival is common, with only 3-7% able to return to their previous level of functioning. Therapeutic hypothermia is an important tool for the treatment of post-anoxic coma after cardiopulmonary resuscitation. It has been shown to reduce mortality and has improved neurological outcomes after cardiac arrest. Nevertheless, hypothermia is underused in critical care units. This manuscript aims to review the mechanism of hypothermia in cardiac arrest survivors and to propose a simple protocol, feasible to be implemented in any critical care unit.

• Cardiac arrest
• cardiopulmonary resuscitation
• hypothermia
• therapeutic

• Antibiotics
• Cardiac arrest
• Hypothermia
• Intensive care
• Pneumonia
• Temperature

• Aged
• Blood Glucose/metabolism
• Blood Pressure
• Coma/complications
• Female
• Heart Arrest/complications
• Heart Arrest/physiopathology
• Heart Arrest/therapy
• Heart Rate
• Hemodynamics
• Hospital Mortality
• Humans
• Hypothermia, Induced
• Lactates/blood
• Male
• Middle Aged
• Monitoring, Physiologic/methods
• Pilot Projects
• Treatment Outcome
• Vascular Resistance

• Cardiopulmonary Resuscitation/methods
• Female
• Humans
• Hypothermia, Induced
• Male
• Out-of-Hospital Cardiac Arrest/therapy

• Arrest
• BIS
• Bispectral index
• CPR
• EEG
• Hypothermia

• Emergency Nursing/methods
• Heart Arrest/nursing
• Humans
• Hypothermia, Induced/methods
• Hypothermia, Induced/nursing
• Male
• Middle Aged
• Nursing Methodology Research
• Patient Selection
• Professional-Family Relations
• Prognosis
• Social Support
• Treatment Outcome

• Body Temperature/physiology
• Clinical Competence
• Critical Care/methods
• Heart Arrest/therapy
• Humans
• Hypothermia, Induced/adverse effects
• Hypothermia, Induced/nursing
• Intensive Care Units
• Male
• Middle Aged
• Nursing Assessment
• Nursing Methodology Research
• Shivering/physiology

• hypothermia
• cardiac arrest
• hypoxic-ischemic encephalopathy
• perinatal asphyxia
• neurological outcome
• intracranial hypertension
• neurocritical care

• Acute Disease
• Critical Care/methods
• Heart Arrest/therapy
• Humans
• Hypothermia, Induced/methods
• Nervous System Diseases/physiopathology
• Nervous System Diseases/therapy