Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Prediction of encephalopathy in perinatal asphyxia score: reaching the unreached.

OBJECTIVES: Neonates who develop moderate to severe encephalopathy following perinatal asphyxia will benefit from therapeutic hypothermia. Current National Institute of Child Health and Human Development (NICHD) criteria for identifying encephalopathic neonates needing therapeutic hypothermia has high specificity. This results in correctly identifying neonates who have already developed moderate to severe encephalopathy but miss out many potential beneficiaries who progress to develop moderate to severe encephalopathy later. The need is therefore not just to diagnose encephalopathy, but to predict development of encephalopathy and extend the therapeutic benefit for all eligible neonates. The primary objective of the study was to develop and validate the statistical model for prediction of moderate to severe encephalopathy following perinatal asphyxia and compare with current NICHD criteria. METHODS: The study was designed as prospective observational study. It was carried out in a single center Level 3 perinatal unit in India. Neonates>35 weeks of gestation and requiring resuscitation at birth were included. Levels of resuscitation and blood gas lactate were used to determine the pre-test probability, Thompson score between 3 and 5 h of life was used to determine post-test probability of developing encephalopathy. Primary outcome measure: Validation of Prediction of Encephalopathy in Perinatal Asphyxia (PEPA) score by Holdout method. RESULTS: A total of 55 babies were included in the study. The PEPA score was validated by Holdout method where the fitted receiver-operating characteristic (ROC) area for the training and test sample were comparable (p=0.758). The sensitivity and specificity of various PEPA scores for prediction of encephalopathy ranged between 74 and 100% in contrast to NICHD criteria which was 42%. PEPA score of 30 had a best combination of sensitivity and specificity of 95 and 89% respectively. CONCLUSIONS: PEPA score has a higher sensitivity than NICHD criteria for prediction of Encephalopathy in asphyxiated neonates.

2019 American Heart Association Focused Update on Pediatric Advanced Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2019 focused update to the American Heart Association pediatric advanced life support guidelines follows the 2018 and 2019 systematic reviews performed by the Pediatric Life Support Task Force of the International Liaison Committee on Resuscitation. It aligns with the continuous evidence review process of the International Liaison Committee on Resuscitation, with updates published when the International Liaison Committee on Resuscitation completes a literature review based on new published evidence. This update provides the evidence review and treatment recommendations for advanced airway management in pediatric cardiac arrest, extracorporeal cardiopulmonary resuscitation in pediatric cardiac arrest, and pediatric targeted temperature management during post-cardiac arrest care. The writing group analyzed the systematic reviews and the original research published for each of these topics. For airway management, the writing group concluded that it is reasonable to continue bag-mask ventilation (versus attempting an advanced airway such as endotracheal intubation) in patients with out-of-hospital cardiac arrest. When extracorporeal membrane oxygenation protocols and teams are readily available, extracorporeal cardiopulmonary resuscitation should be considered for patients with cardiac diagnoses and in-hospital cardiac arrest. Finally, it is reasonable to use targeted temperature management of 32°C to 34°C followed by 36°C to 37.5°C, or to use targeted temperature management of 36°C to 37.5°C, for pediatric patients who remain comatose after resuscitation from out-of-hospital cardiac arrest or in-hospital cardiac arrest.

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis.

OBJECTIVES: This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients. METHODS: We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed. RESULTS: Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = - 90.45[- 167.57, - 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = - 0.68[- 1.03, - 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I2 = 0%), but EC reduced the length of stay in ICU (MD = - 1.83[- 3.45, - 0.21], p = 0.03, I2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients' cardiac arrest to achieve the target temperature (MD = - 46.64[- 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I2 = 0%). CONCLUSIONS: Among adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients' ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.

System Specific Effects of Therapeutic Hypothermia with Neonatal Encephalopathy: Pearls for Clinicians.

Neonatal encephalopathy (NE) is defined as a condition of impaired neurological function often caused by a peripartum event that impairs gas exchange resulting in hypoxia, hypercapnia, cerebral ischemia, and metabolic acidosis. NE is a significant cause of neonatal morbidity and mortality. Therapeutic hypothermia (TH) is the standard of care for the treatment of moderate and severe NE and has significantly improved long-term outcomes for affected infants. There are extensive systemic physiologic effects associated with TH that clinicians need to be aware of to optimize care for these infants. There is a paucity of literature that comprehensively identifies causal relationships between the physiologic and biochemical effects of TH. This can leave neonatal clinicians devoid of a comprehensive understanding of the medical management of NE. Therefore, this article seeks to help fill this gap, improve clinician knowledge base, and ultimately improve the care of infants undergoing TH.

Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest: an analysis of the TTH48 trial.

BACKGROUND: The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. RESULTS: A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1-4.0] vs. 4.2 [2.7-6.0] h, p < 0.001), but temperature was also lower on admission (35.0 [34.2-35.6] vs. 35.3 [34.5-35.8]°C; p = 0.02) and cooling rate was similar (0.4 [0.2-0.8] vs. 0.4 [0.2-0.6]°C/h; p = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4-0.9] vs. 0.7 [0.5-1.0]°C; p = 0.007), as was rewarming rate (0.31 [0.22-0.44] vs. 0.37 [0.29-0.49]°C/hour; p = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p = 0.24) between type of devices. CONCLUSIONS: Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.

Temporal trends in the use of targeted temperature management after cardiac arrest and association with outcome: insights from the Paris Sudden Death Expertise Centre.

PURPOSE: Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome. METHODS: We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale. RESULTS: Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 (P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% (P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 (P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome. CONCLUSIONS: We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in "no flow" duration.

Renal function after out-of-hospital cardiac arrest; the influence of temperature management and coronary angiography, a post hoc study of the target temperature management trial.

BACKGROUND: To elucidate the incidence of acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) and to examine the impact of target temperature management (TTM) and early coronary angiography on renal function. METHODS: Post hoc analysis of the TTM trial, a multinational randomised controlled trial comparing target temperature of 33 °C versus 36 °C in patients with return of spontaneous circulation after OHCA. The impact of TTM and early angiography (within 6 h of OHCA) versus late or no angiography on the development of AKI during the 7-day period after OHCA was analysed. AKI was defined according to modified KDIGO criteria in patients surviving beyond day 2 after OHCA. RESULTS: Following exclusions, 853 of 939 patients enrolled in the main trial were analysed. Unadjusted analysis showed that significantly more patients in the 33 °C group had AKI compared to the 36 °C group [211/431 (49%) versus 170/422 (40%) p = 0.01], with a worse severity (p = 0.018). After multivariable adjustment, the difference was not significant (odds ratio 0.75, 95% confidence interval 0.54-1.06, p = 0.10]. Five hundred seventeen patients underwent early coronary angiography. Although the unadjusted analysis showed less AKI and less severe AKI in patients who underwent early angiography compared to patients with late or no angiography, in adjusted analyses, early angiography was not an independent risk factor for AKI (odds ratio 0.73, 95% confidence interval 0.50-1.05, p = 0.09). CONCLUSIONS: In OHCA survivors, TTM at 33 °C compared to management at 36 °C did not show different rates of AKI and early angiography was not associated with an increased risk of AKI. TRIAL REGISTRATION: NCT01020916 . Registered on www.ClinicalTrials.gov 26 November 2009 (main trial).

Beyond dichotomy: patterns and amplitudes of SSEPs and neurological outcomes after cardiac arrest.

BACKGROUND: We hypothesized that the absence of P25 and the N20-P25 amplitude in somatosensory evoked potentials (SSEPs) have higher sensitivity than the absence of N20 for poor neurological outcomes, and we evaluated the ability of SSEPs to predict long-term outcomes using pattern and amplitude analyses. METHODS: Using prospectively collected therapeutic hypothermia registry data, we evaluated whether cortical SSEPs contained a negative or positive short-latency wave (N20 or P25). The N20-P25 amplitude was defined as the largest difference in amplitude between the N20 and P25 peaks. A good or poor outcome was defined as a Glasgow-Pittsburgh Cerebral Performance Category (CPC) score of 1-2 or 3-5, respectively, 6 months after cardiac arrest. RESULTS: A total of 192 SSEP recordings were included. In all patients with a good outcome (n = 51), both N20 and P25 were present. Compared to the absence of N20, the absence of N20-P25 component improved the sensitivity for predicting a poor outcome from 30.5% (95% confidence interval [CI], 23.0-38.8%) to 71.6% (95% CI, 63.4-78.9%), while maintaining a specificity of 100% (93.0-100.0%). Using an amplitude < 0.64 µV, i.e., the lowest N20-P25 amplitude in the good outcome group, as the threshold, the sensitivity for predicting a poor neurological outcome was 74.5% (95% CI, 66.5-81.4%). Using the highest N20-P25 amplitude in the CPC 4 group (2.31 µV) as the threshold for predicting a good outcome, the sensitivity and specificity were 52.9% (95% CI, 38.5-67.1%) and 96.5% (95% CI, 91.9-98.8%), respectively. The predictive performance of the N20-P25 amplitude was good, with an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.90-0.97). The absence of N20 was statistically inferior regarding outcome prediction (p < 0.05), and amplitude analysis yielded significantly higher AUC values than did the pattern analysis (p < 0.05). CONCLUSIONS: The simple pattern analysis of whether the N20-P25 component was present had a sensitivity comparable to that of the N20-P25 amplitude for predicting a poor outcome. Amplitude analysis was also capable of predicting a good outcome.

Effectiveness of Two Targeted Temperature Management Methods After Pediatric Postcardiac Arrest: A Multicenter International Study.

OBJECTIVES: It is currently recommended that after return of spontaneous circulation following cardiac arrest, fever should be prevented using TTM through a servo-controlled system. This technology is not yet available in many global settings, where manual physical measures without servo-control is the only option. Our aim was to compare feasibility, safety and quality assurance of servo-controlled system versus no servo-controlled system cooling, TTM protocols for cooling, maintenance and rewarming following return of spontaneous circulation after cardiac arrest in children. DESIGN: Prospective, multicenter, nonrandomized, study. SETTING: PICUs of 20 hospitals in South America, Spain, and Italy, 2012-2014. PATIENTS: Under 18 years old with a cardiac arrest longer than 2 minutes, in coma and surviving to PICU admission requiring mechanical ventilation were included. METHODS: TTM to 32-34°C was performed by prospectively designed protocol across 20 centers, with either servo-controlled system or no servo-controlled system methods, depending on servo-controlled system availability. We analyzed clinical data, cardiac arrest, temperature, mechanical ventilation duration, length of hospitalization, complications, survival, and neurologic outcomes at 6 months. PRIMARY OUTCOME: feasibility, safety and quality assurance of the cooling technique and secondary outcome: survival and Pediatric Cerebral Performance Category at 6 months. MEASUREMENTS AND MAIN RESULTS: Seventy patients were recruited, 51 of 70 TTM (72.8%) with servo-controlled system. TTM induction, maintenance, and rewarming were feasible in both groups. Servo-controlled system was more effective than no servo-controlled system in maintaining TTM (69 vs 60%; p = 0.004). Servo-controlled system had fewer temperatures above 38.1°C during the 5 days of TTM (0.1% vs 2.9%; p < 0.001). No differences in mortality, complications, length of mechanical ventilation and of stay, or neurologic sequelae were found between the two groups. CONCLUSIONS: TTM protocol (for cooling, maintenance and rewarming) following return of spontaneous circulation after cardiac arrest in children was feasible and safe with both servo-controlled system and no servo-controlled system techniques. Achieving, maintaining, and rewarming within protocol targets were more effective with servo-controlled system versus no servo-controlled system techniques.

Safety, Feasibility, and Efficiency of a New Cooling Device Using Intravenous Cold Infusions for Fever Control.

BACKGROUND: Fever control plays a key role in therapy of patients with acute brain injury. The infusion of cold saline could serve as an alternative or additional method for targeted temperature management. However, it is difficult to estimate the amount of fluid required to achieve normothermia merely on the basis of body weight. There is no standardized load management regarding the administration of cold saline, and no closed-loop systems based on continuous temperature-controlled feedback are available. The primary purpose of the present study was to evaluate the feasibility, efficacy, and safety of a new automated fluid infusion system. METHODS: Twelve patients with acute brain injury and febrile episodes were treated with the automated infusion device tempedy (seiratherm GmbH, Herzogenaurach, Germany). Patients were included if bladder temperature still was ≥ 37.9 °C after administration of antipyretic medication, cold washing solutions, and ice packs more than 2 h earlier. The efficacy was examined by measuring the time and amount of fluid needed to reach and maintain target temperature. Feasibility and safety were assessed based on recording any technical difficulties with the new device and the occurrence of clinical signs of fluid overload such as acute pulmonary edema, electrolyte disturbances, or acid-base dysfunction. RESULTS: The mean time was 73 min (range from 15 to 330 min) and 1650 ml the mean amount of fluid (21.2 ml/kg; SD 28.5 ml/kg) to reach the target temperature. The mean total fluid balance to reach and maintain the target temperature in the first 12 h was 1350 ml (SD 1550 ml). In the first 12 h 89.4% of the time temperature values were in the target range (median 95.3%, range 83.8-10%). No clinical signs of fluid overload such as an acute pulmonary edema or device-related adverse events occurred. CONCLUSION: Target temperature management with the new automated infusion device is feasible. Although we provided first data regarding safety, further controlled randomized studies are needed to evaluate the long-time safety, as well as the best indications and timing for this cooling device.

A Novel Technique for Ice Water Immersion in Severe Drug-Induced Hyperthermia in the Emergency Department.

BACKGROUND: Methamphetamine can cause life-threatening hyperthermia and treatment must be aggressive and rapid. There are multiple methods of cooling, with cold-water immersion being one of the most effective treatment options. However, this method is technically difficult to institute in the emergency department setting. CASE REPORT: We report 2 patients who presented with life-threatening hyperthermia from methamphetamine and were treated in the emergency department with a novel technique of using a body bag filled with ice water to perform rapid cooling. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This method of cooling is a safe, rapid, and efficacious method for emergency physicians to perform cold water immersion in the department.

Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial.

BACKGROUND: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study. METHODS: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0 °C-34.0 °C) or fever control (35.5 °C-37.0 °C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR - HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death. RESULTS: Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR < 18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR < 80 and %HR ≥ 18.6) developed only 22.8% (p = 0.04). CONCLUSIONS: Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.

The efficacy and safety of pre-hospital cooling after out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Mild therapeutic hypothermia (TH), or targeted temperature management, improves survival and neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA). International guidelines strongly support initiating TH for all eligible individuals presenting with OHCA; however, the timing of cooling initiation remains uncertain. This systematic review and meta-analysis was conducted with all available randomised controlled trials (RCTs) included to explore the efficacy and safety of initiating pre-hospital TH in patients with OHCA. METHODS: The MEDLINE and Cochrane databases were searched from inception to October 2017. Inclusion criteria for full-text review included RCTs comparing pre-hospital TH with no pre-hospital TH after cardiac arrest, patients > 14 years of age with documented cardiac arrest from any rhythm, and outcome data that included survival to hospital discharge and temperature at hospital arrival. Results of retrieved studies were compared through meta-analysis using random effects modelling. RESULTS: A total of 10 trials comprising 4220 patients were included. There were no significant differences between the two arms for the primary outcome of neurological recovery (risk ratio [RR] 1.04, 95% CI 0.93-1.15) or the secondary outcome of survival to hospital discharge (RR 1.01, 95% CI 0.92-1.11). However, there was a significantly lower temperature at hospital arrival in patients receiving pre-hospital TH (mean difference - 0.83, 95% CI - 1.03 to - 0.63). Pre-hospital TH significantly increased the risk of re-arrest (RR 1.19, 95% CI 1.00 to 1.41). No survival differences were observed among subgroups of patients who received intra-arrest TH vs post-arrest TH or who had shockable vs non-shockable rhythms. CONCLUSIONS: Pre-hospital TH after OHCA effectively decreases body temperature at the time of hospital arrival. However, it does not improve rates of survival with good neurological outcome or overall survival and is associated with increased rates of re-arrest.

Acute kidney injury and mild therapeutic hypothermia in patients after cardiopulmonary resuscitation - a post hoc analysis of a prospective observational trial.

BACKGROUND: The aim of this study was to investigate the influence of mild therapeutic hypothermia (MTH) on the incidence of and recovery from acute kidney injury (AKI). METHODS: Patients who had undergone successful cardiopulmonary resuscitation (CPR) were included. Serum creatinine and cystatin C were measured at baseline, daily up to 5 days and at ICU discharge. AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. MTH was applied for 24 h targeting a temperature of 33 °C. Neurological outcome was assessed with the Cerebral Performance Categories score at hospital discharge. RESULTS: 126 patients were included in the study; 73 patients (58%) developed AKI. Patients treated with MTH had a significantly lower incidence of AKI as compared to normothermia (NT) (44 vs. 69%; p = 0.004). Patients with less favourable neurological outcomes had a significantly higher rate of AKI, although when treated with MTH the occurrence of AKI was reduced (50 vs. 80%; p = 0.017). Furthermore, MTH treatment was accompanied by significantly lower creatinine levels on day 0-1 and at ICU discharge (day 0: 1.12 (0.90-1.29) vs. 1.29 (1.00-1.52) mg/dl; p = 0.016) and lower cystatin C levels on day 0-3 and at ICU discharge (day 0: 0.88 (0.77-1.10) vs. 1.29 (1.06-2.16) mg/l; p < 0.001). CONCLUSIONS: Mild therapeutic hypothermia seems to have a protective effect against the development of AKI and on renal recovery. This may be less pronounced in patients with a favourable neurological outcome.