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Extracorporeal life support rewarming rate is associated with survival with good neurological outcome in accidental hypothermia
Abstract
OBJECTIVES
Favourable outcomes have been demonstrated after extracorporeal life support (ECLS) facilitated rewarming for severe accidental hypothermia. The clinical impact of varying rewarming rates however is unclear. We sought to quantify the change in the probability of good neurological outcome with ECLS rewarming rate and identify the optimal rewarming rate threshold.
METHODS
We performed a secondary analysis of the International ACcidental Hypothermia Extracorporeal Life Support Collaborators, an individual patient data data set (n = 658) for ECLS-assisted rewarming for accidental hypothermia. The independent variable of interest was rewarming rate. The primary outcome was survival with good neurological status. We applied an adjusted marginal effects model to quantify the probability of good neurological outcome over clinically observed rewarming rates. We examined strata defined by sex, initial potassium level and history of asphyxiation.
RESULTS
Of 658 cases, the median age and initial core temperature were 36 years (22–55) and 24.5°C (22.1–26.2) respectively; 190 (29%) were female, and 547 (83%) had a non-perfusing initial cardiac rhythm. The mean rewarming rate was 7.0°C/h. The median ECLS duration was 5.8 h (range: 0.5–158 h). The overall survival was 46% (n = 303/658), and good neurological outcome was 40% (n = 265/658). The median intensive care unit and hospital length of stay was 5 days (range: 1–35 days) and 18 days (range: 1–106 days), respectively. Marginal effects analysis demonstrated a 1.9% decrease in the probability of survival with good neurological outcome for each 1°C/h increase in rewarming. Across the reported range of rewarming rates (0.05–30.8°C/h), the probability of good neurological outcome declined from 49.6% to 4.1% for an average patient. The relationship was similar within various subgroups. The optimal cut-off threshold for the rate of rewarming to distinguish between a good and poor neurological outcome was ≤5.0°C/h.
CONCLUSIONS
Among cases with severe accidental hypothermia treated with ECLS, slower rewarming rates are associated with improved survival with good neurological outcomes. Slow rewarming, at rates ≤5.0°C/h, may improve clinical outcomes.
... The rewarming rate is calculated as a change of Tc per unit of time during ECMO therapy ( • C/h). The optimal rewarming rate is still unknown for hypothermic patients but is usually targeted to ≤5 • C/h [38]. Faster rewarming rates until the return of spontaneous circulation may be recommended, but 10 • C/h should not be exceeded, followed by slower rewarming of about 1-2 • C/h. ...
... ECMO protocols routinely include the use of heparin in order to counteract the development of the prothrombotic state and decrease the risk of pump malfunction, oxygenator failure and thromboembolic events, including stroke or pulmonary embolism [38][39][40][41]. Bolus of unfractionated heparin should be administered (50-100 units per kg) at the time of cannulation and then by continuous infusion [35,39]. ...
Accidental hypothermia, defined as an unintentional drop of the body core temperature below 35 °C, is one of the causes of cardiocirculatory instability and reversible cardiac arrest. Currently, extracorporeal life support (ECLS) rewarming is recommended as a first-line treatment for hypothermic cardiac arrest patients. The aim of the ECLS rewarming is not only rapid normalization of core temperature but also maintenance of adequate organ perfusion. Veno-arterial extracorporeal membrane oxygenation (ECMO) is a preferred technique due to its lower anticoagulation requirements and potential to prolong circulatory support. Although highly efficient, ECMO is acknowledged as an invasive treatment option, requiring experienced medical personnel and is associated with the risk of serious complications. In this review, we aimed to discuss the clinical aspects of ECMO management in severely hypothermic cardiac arrest patients.
... 37 Besides, marginal effects analyses were performed to explore whether the relationship between SGLT2i/DPP4i exposure and syncope was modulated by the age at initial drug exposure, baseline Charlson comorbidity index, number of previous hospit alizations , and duration of T2DM. 38 Additionally, an exploratory three-arm ( SGLT2i vs. DPP4i vs. glucagon-like peptide-1 receptor agonist) as-treated analysis was conducted. Last but not least, further falsification tests using venous thromboembolism ( VTE, i.e. deep vein thrombosis or pulmonary embolism) as a negative control endpoint were performed to determine the potential of the study design to identify likely false associations. ...
Background and Aims
Syncope and post-syncopal adverse events have led to a heavy health and economic
burden in the world. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) has demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects between SGLT2i and dipeptidyl peptidase-4 inhibitor (DPP4i) on new-onset syncope.
Methods
This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus
(T2DM) patients treated with SGLT2i or DPP4i between January 1st, 2015, and December 31st, 2020, in Hong Kong, China. The outcomes were new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality.
Results
After matching, a total of 37502 patients with T2DM were included (18751 SGLT2i users versus 18751 DPP4i users). During a median follow-up of 5.56 years, compared to DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope (HR, 0.49; 95%CI [0.41-0.57], P<0.001), 65% lower risk of cardiovascular mortality (HR, 0.35; 95%CI [0.26-0.46], P<0.001), and a 70% lower risk of all-cause mortality (HR, 0.30; 95%CI [0.26-0.34], P<0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR, 0.70; 95%CI [0.58-0.85], P<0.001), canagliflozin (HR, 0.48; 95%CI [0.36-0.63], P<0.001) and ertugliflozin (HR, 0.45; 95%CI [0.30-0.68], P<0.001), but was attenuated for empagliflozin (HR, 0.79; 95%CI [0.59-1.05], P=0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared to DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline.
Conclusions
Compared to DPP4i, SGLT2i was associated with a significantly lower risk of new onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden. Our findings may potentially provide some insights into the preventive strategy of incident syncope.
... Rewarming rates reported in accidental hypothermia case series range from 1.5 to 10°C/h, and as in cardiac surgery avoiding hyperthermia appears to be essential for optimal neurocognitive outcome, although optimal rewarming rate remains unknown (Grigore et al., 2009). Weaning from CPB rewarming at core temperatures > 31°C is recommended (Paal et al., 2016), and a slower CPB rewarming rate (≤ 5.0°C/h) in severe accidental hypothermia was associated with improved survival and good neurological outcomes (Saczkowski et al., 2021). ...
Introduction: Using a porcine model of accidental immersion hypothermia and hypothermic cardiac arrest (HCA), the aim of the present study was to compare effects of different rewarming strategies on CPB on need for vascular fluid supply, level of cardiac restitution, and cerebral metabolism and pressures.
Materials and Methods: Totally sixteen healthy, anesthetized castrated male pigs were immersion cooled to 20°C to induce HCA, maintained for 75 min and then randomized into two groups: 1) animals receiving CPB rewarming to 30°C followed by immersion rewarming to 36°C (CPB30, n = 8), or 2) animals receiving CPB rewarming to 36°C (CPB36, n = 8). Measurements of cerebral metabolism were collected using a microdialysis catheter. After rewarming to 36°C, surviving animals in both groups were further warmed by immersion to 38°C and observed for 2 h.
Results: Survival rate at 2 h after rewarming was 5 out of 8 animals in the CPB30 group, and 8 out of 8 in the CPB36 group. All surviving animals displayed significant acute cardiac dysfunction irrespective of rewarming method. Differences between groups in CPB exposure time or rewarming rate created no differences in need for vascular volume supply, in variables of cerebral metabolism, or in cerebral pressures and blood flow.
Conclusion: As 3 out of 8 animals did not survive weaning from CPB at 30°C, early weaning gave no advantages over weaning at 36°C. Further, in surviving animals, the results showed no differences between groups in the need for vascular volume replacement, nor any differences in cerebral blood flow or pressures. Most prominent, after weaning from CPB, was the existence of acute cardiac failure which was responsible for the inability to create an adequate perfusion irrespective of rewarming strategy.
... Practical approaches to patient management with ECPR and ECLS rewarming have been described [88,131,147]. Additional measures, such as vigorous resuscitation with isotonic fluids and the use of vasopressors are usually needed to maintain mean arterial pressure between 50 and 70 mmHg. ...
Accidental hypothermia is an unintentional drop of core temperature below 35 °C. Annually, thousands die of primary hypothermia and an unknown number die of secondary hypothermia worldwide. Hypothermia can be expected in emergency patients in the prehospital phase. Injured and intoxicated patients cool quickly even in subtropical regions. Preventive measures are important to avoid hypothermia or cooling in ill or injured patients. Diagnosis and assessment of the risk of cardiac arrest are based on clinical signs and core temperature measurement when available. Hypothermic patients with risk factors for imminent cardiac arrest (temperature < 30 °C in young and healthy patients and <32 °C in elderly persons, or patients with multiple comorbidities), ventricular dysrhythmias, or systolic blood pressure < 90 mmHg) and hypothermic patients who are already in cardiac arrest, should be transferred directly to an extracorporeal life support (ECLS) centre. If a hypothermic patient arrests, continuous cardiopulmonary resuscitation (CPR) should be performed. In hypothermic patients, the chances of survival and good neurological outcome are higher than for normothermic patients for witnessed, unwitnessed and asystolic cardiac arrest. Mechanical CPR devices should be used for prolonged rescue, if available. In severely hypothermic patients in cardiac arrest, if continuous or mechanical CPR is not possible, intermittent CPR should be used. Rewarming can be accomplished by passive and active techniques. Most often, passive and active external techniques are used. Only in patients with refractory hypothermia or cardiac arrest are internal rewarming techniques required. ECLS rewarming should be performed with extracorporeal membrane oxygenation (ECMO). A post-resuscitation care bundle should complement treatment.
... Furthermore, a recent retrospective study showed that a slower ECMO rewarming rate was associated with a better survival rate, 18 while another study showed the opposite result. 19 The optimal ECMO rewarming rate thus remains unclear. ...
Introduction
Accidental hypothermia (AH) is a rare but critical disease, leading to death in severe cases. In recent decades, extracorporeal membrane oxygenation (ECMO) has been successfully used to rewarm hypothermic patients with cardiac arrest or circulation instability. However, data on the efficacy of rewarming using ECMO for patients with AH are limited. Therefore, a large-scale, multicentre, prospective study is warranted. The primary objective of this study will be to clarify the effectiveness of rewarming using ECMO for patients with AH. Our secondary objectives will be to compare the incidence of adverse effects between ECMO rewarming and non-ECMO rewarming and to identify the most appropriate management of ECMO for AH.
Methods and analyses
The Intensive Care with ExtraCorporeal membrane oxygenation Rewarming in Accidentally Severe Hypothermia study is taking place in 35 tertiary emergency medical facilities in Japan. The inclusion criteria are patients ≥18 years old with a body temperature ≤32°C. We will include patients with AH who present to the emergency department from December 2019 to March 2022. The research personnel at each hospital will collect several variables, including patient demographics, rewarming method, ECMO data and complications. Our primary outcome is to compare the 28-day survival rate between the ECMO and non-ECMO (other treatments) groups among patients with severe AH. Our secondary outcomes are to compare the following values between the ECMO and non-ECMO groups: length of stay in the intensive-care unit and complications. Furthermore, in patients with cardiac arrest, the Cerebral Performance Category score at discharge will be compared between both groups.
Ethics and dissemination
This study received research ethics approval from Asahikawa Medical University (18194 and 19115). The study was approved by the institutional review board of each hospital, and the requirement for informed consent was waived due to the observational nature of the study.
Trial registration number
UMIN000036132.
... 87 The target rewarming rate during ECLS in accidental hypothermia should be ≤5ºC/h. 89 It is recommended to start rewarming in 5-10 minutes time intervals after cannulation to ensure the accurate functioning of all devices. The heat exchanger should be set at a maximum of 37°C to prevent cerebral overheating. ...
Severely hypothermic patients, especially suffering cardiac arrest, require highly specialized treatment. The most common problems affecting the recognition and treatment seem to be awareness, logistics, and proper planning. In severe hypothermia, pathophysiologic changes occur in the cardiovascular system leading to dysrhythmias, decreased cardiac output, decreased central nervous system electrical activity, cold diuresis, and noncardiogenic pulmonary edema. Cardiac arrest, multiple organ dysfunction, and refractory vasoplegia are indicative of profound hypothermia. The aim of these narrative reviews is to describe the peculiar pathophysiology of patients suffering cardiac arrest from accidental hypothermia. We describe the good chances of neurologic recovery in certain circumstances, even in patients presenting with unwitnessed cardiac arrest, asystole, and the absence of bystander cardiopulmonary resuscitation. Guidance on patient selection, prognostication, and treatment, including extracorporeal life support, is given.
Paediatric resuscitation is a key skill for anyone in medicine who is involved in the care of children. Basic and advance paediatric life support courses are crucial in teaching those skills nationwide in a way that is memorable, protocolised and standardised. These courses are vital in the dissemination and upkeep of both theoretical and practical knowledge of paediatric resuscitation, with their primary aim being the return of spontaneous circulation. While sustaining life is important, preserving a life with quality, one with good functional and neurological outcomes should be the gold standard of any resuscitative attempt. Good neurological outcomes are dependent, in large part, on how well the postresuscitation stage is managed. This stage does not start in the intensive care unit, it starts at the point at which spontaneous circulation has been reinstated. The aim of this paper is to provide a basic overview of the main strategies that should be followed in order to minimise secondary brain injury after successful resuscitation attempts.
The lack of a consensus of accepted prognostic factors in hypothermia suggests an additional factor has been overlooked. Delayed rewarming thrombocytopenia (DRT) is a novel candidate for such a role. At body temperature, platelets undergoing a first stage of aggregation are capable of progression to a second irreversible stage of aggregation. However, we have shown that the second stage of aggregation does not occur below 32°C and that this causes the first stage to become augmented (first-stage platelet hyperaggregation). In aggregometer studies performed below 32°C, the use of quantities of ADP that cause a marked first-stage hyperaggregation can cause an augmented second-stage activation of the platelets during rewarming (second-stage platelet hyperaggregation). In vivo, after 24 hours of hypothermia, platelets on rewarming seem to undergo second-stage hyperaggregation, from ADP released from erythrocytes, leading to life-threatening thrombocytopenia. This hyperaggregation is avoidable if heparin is given before the hypothermia or if aspirin, alcohol or platelet transfusion is given during the hypothermia before reaching 32°C on rewarming. Many of the open questions existing in this field are explained by DRT. Prevention and treatment of DRT could be of significant value in preventing rewarming deaths and some cases of rescue collapse. Performing platelet counts during rewarming will demonstrate potentially fatal thrombocytopenia and enable treatment with platelet infusions aspirin or alcohol.
Objectives:
Extracorporeal membrane oxygenation (ECMO) is recommended in adults with drowning-associated hypothermia and out-of-hospital cardiac arrest (OHCA). Our experience of managing a drowned 2-year-old girl with hypothermia (23°C) and cardiac arrest (58 min) prompted this summary using the CAse REport (CARE) guideline to address the question of optimal rewarming procedure in such patients.
Design/patients:
Following the CARE guideline, we identified 24 reports in the "PubMed database" describing children less than or equal to 6 years old with a temperature less than or equal to 28°C who had been rewarmed using conventional intensive care ± ECMO. Adding our patient, we were able to analyze a total of 57 cases.
Main results:
The two groups (ECMO vs non-ECMO) differed with respect to submersion time, pH and potassium but not age, temperature or duration of cardiac arrest. However, 44 of 44 in the ECMO group were pulseless on arrival versus eight of 13 in the non-ECMO group. Regarding survival, 12 of 13 children (92%) undergoing conventional rewarming survived compared with 18 of 44 children (41%) undergoing ECMO. Among survivors, 11 of 12 children (91%) in the conventional group and 14 of 18 (77%) in the ECMO group had favorable outcome. We failed to identify any correlation between "rewarming rate" and "outcome."
Conclusions:
In this summary analysis, we conclude that conventional therapy should be initiated for drowned children with OHCA. However, if this therapy does not result in return of spontaneous circulation, a discussion of withdrawal of intensive care might be prudent when core temperature has reached 34°C. We suggest further work is needed using an international registry.
Aim
To assess the impact of the occurrence of cardiac arrest associated with initial management on the outcome of severely hypothermic patients who were rewarmed with Extracorporeal Life Support (ECLS).
Methods
We collected the individual data of patients in a state of severe accidental hypothermia who were found with spontaneous circulation and rewarmed with ECLS, from cardiac surgery departments. Patients were divided into two groups: those with a subsequent cardiac arrest (RC group); and those with the retained circulation (HT3 group), and compared by using a matched-pair analysis. The mortality rates and the neurological status in survivors were compared as the main outcomes. The difference in the risk of death between the HT3 and RC groups was calculated.
Results
A total of 124 patients were included into the study: 45 in the HT3 group and 79 in the RC group. The matched cohorts consisted of 45 HT3 patients and 45 RC patients. The mortality rate in both groups was 24% and 49% (p = 0.02) respectively; the relative risk of death was 2.0 (p = 0.02). ICU length of stay was significantly longer in the RC group (p < 0.001). Factors associated with survival in the HT3 group included patient age, rewarming rate, and blood BE; while in the RC group, patient age and lactate concentration.
Conclusions
The occurrence of rescue collapse is linked to a doubling of the risk of death in severely hypothermic patients. Procedures which are known as potential triggers of rescue collapse should be performed with special attention, including in conscious patients.
Stroke is a leading cause of disability and death, yet effective treatments for acute stroke has been very limited. Thus far, tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients, yet its application is only applicable to less than 4–5% of stroke patients due to the narrow therapeutic window (< 4.5 hours after the onset of stroke) and the high risk of hemorrhagic transformation. Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia, also known as targeted temperature management, can be a promising therapy for patients with different types of stroke. Moreover, the success in animal models using pharmacologically induced hypothermia (PIH) has gained increasing momentum for clinical translation of hypothermic therapy. This review provides an updated overview of the mechanisms and protective effects of therapeutic hypothermia, as well as the recent development and findings behind PIH treatment. It is expected that a safe and effective hypothermic therapy has a high translational potential for clinical treatment of patients with stroke and other CNS injuries.
In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: No Recommendation No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence.
Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Temperature variations in cells, tissues and organs may occur in a number of circumstances. We report here that reducing temperature of cells in culture to 25°C for 5 days followed by a rewarming to 37°C affects cell biology and induces a cellular stress response. Cell proliferation was almost arrested during mild hypothermia and not restored upon returning to 37°C. The expression of cold shock genes, CIRBP and RBM3, was increased at 25°C and returned to basal level upon rewarming while that of heat shock protein HSP70 was inversely regulated. An activation of pro-apoptotic pathways was evidenced by FACS analysis and increased Bax/Bcl2 and BclXS/L ratios. Concomitant increased expression of the autophagosome-associated protein LC3II and AKT phosphorylation suggested a simultaneous activation of autophagy and pro-survival pathways. However, a large proportion of cells were dying 24 hours after rewarming. The occurrence of DNA damage was evidenced by the increased phosphorylation of p53 and H2AX, a hallmark of DNA breaks. The latter process, as well as apoptosis, was strongly reduced by the radical oxygen species (ROS) scavenger, N-acetylcysteine, indicating a causal relationship between ROS, DNA damage and cell death during mild cold shock and rewarming. These data bring new insights into the potential deleterious effects of mild hypothermia and rewarming used in various research and therapeutical fields.
The use of biomarkers is of ever-increasing importance in clinical diagnosis of disease. In practice, a cutpoint is required for dichotomizing naturally continuous biomarker levels to distinguish persons at risk of disease from those who are not. Two methods commonly used for establishing the "optimal" cutpoint are the point on the receiver operating characteristic curve closest to (0,1) and the Youden index, J. Both have sound intuitive interpretations--the point closest to perfect differentiation and the point farthest from none, respectively--and are generalizable to weighted sensitivity and specificity. Under the same weighting of sensitivity and specificity, these two methods identify the same cutpoint as "optimal" in certain situations but different cutpoints in others. In this paper, the authors examine situations in which the two criteria agree or disagree and show that J is the only "optimal" cutpoint for given weighting with respect to overall misclassification rates. A data-driven example is used to clarify and demonstrate the magnitude of the differences. The authors also demonstrate a slight alteration in the (0,1) criterion that retains its intuitive meaning while resulting in consistent agreement with J. In conclusion, the authors urge that great care be taken when establishing a biomarker cutpoint for clinical use.
Severe traumatic brain injury (TBI) has been increasing with greater incidence of injuries from traffic or sporting accidents. Although there are a number of animal models of TBI using progesterone for head injury, the effects of progesterone on neurologic outcome of acute TBI patients remain unclear. The aim of the present clinical study was to assess the longer-term efficacy of progesterone on the improvement in neurologic outcome of patients with acute severe TBI.
A total of 159 patients who arrived within 8 hours of injury with a Glasgow Coma Score </= 8 were enrolled in the study. A prospective, randomized, placebo-controlled trial of progesterone was conducted in the Neurotrauma Center of our teaching hospital. The patients were randomized to receive either progesterone or placebo. The primary endpoint was the Glasgow Outcome Scale score 3 months after brain injury. Secondary efficacy endpoints included the modified Functional Independence Measure score and mortality. In a follow-up protocol at 6 months, the Glasgow Outcome Scale and the modified Functional Independence Measure scores were again determined.
Of the 159 patients randomized, 82 received progesterone and 77 received placebo. The demographic characteristics, the mechanism of injury, and the time of treatment were compared for the two groups. After 3 months and 6 months of treatment, the dichotomized Glasgow Outcome Scale score analysis exhibited more favorable outcomes among the patients who were given progesterone compared with the control individuals (P = 0.034 and P = 0.048, respectively). The modified Functional Independence Measure scores in the progesterone group were higher than those in the placebo group at both 3-month and 6-month follow-up (P < 0.05 and P < 0.01). The mortality rate of the progesterone group was significantly lower than that of the placebo group at 6-month follow-up (P < 0.05). The mean intracranial pressure values 72 hours and 7 days after injury were lower in the progesterone group than in the placebo group, but there was no statistical significance between the two groups (P > 0.05). Instances of complications and adverse events associated with the administration of progesterone were not found.
Our data suggest that acute severe TBI patients with administration of progesterone hold improved neurologic outcomes for up to 6 months. These results provide information important for further large and multicenter clinical trials on progesterone as a promising neuroprotective drug.
ACTRN12607000545460.
Objective:
Data demonstrating benefit of advanced life support (ALS) practitioners for out-of-hospital cardiac arrest (OHCA) is conflicting. In our tiered emergency medical services (EMS) system, we sought to determine if the ALS response interval was associated with patient outcomes.
Methods:
We performed a secondary analysis of consecutive adult OHCAs (2006-2016) in British Columbia. Primary and secondary outcomes were survival and favorable neurological outcomes (mRS ≤ 3) at hospital discharge. Logistic regression estimated the association of ALS response interval (911 call-to-ALS arrival, continuous and categorical analyses) and outcomes, adjusting for first EMS response interval, and other clinical characteristics. We calculated the optimal time threshold to differentiate "early" vs "late" ALS response intervals for a binary comparison.
Results:
Of 12,722 included cases, 12% survived to discharge. Median response interval was 6.4 min (IQR 5.2-8.3) for the first EMS unit and 11.8 min (IQR 8.7-16.5) for ALS. ALS response interval (per minute) was associated with decreased survival (adjusted OR 0.98, 95% CI 0.96-0.99) and favourable neurological outcome (0.98, 95% CI 0.97-0.99). ALS response ≤10 min (the optimal threshold) was associated with improved survival (adjusted OR 1.46; 95% CI 1.27-1.68) and favourable neurological outcomes (adjusted OR 1.41; 95% CI 1.18-1.68).
Conclusion:
In our tiered EMS system, earlier ALS arrival was associated with improved survival and favorable neurological outcomes. ALS attendance within 10 min of the 9-1-1 call in tiered systems of prehospital care may improve patient outcomes and serve as a quality metric.
Objectives:
To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial.
Design:
Retrospective cohort study (January 2005 to December 2016).
Setting:
The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs.
Patients:
Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest.
Interventions:
The primary exposure of interest was admission before versus after publication of the target temperature management trial.
Measurements and main results:
The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± SD lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89-1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, -1.8 to -0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, -1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, -0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16-1.57]).
Conclusions:
The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.
Background:
Extra-corporeal life support (ECLS) is a life-saving intervention for patients with hypothermia induced cardiac arrest or severe cardiovascular instability. However, its application is highly variable due to a paucity of data in the literature to guide practice. Current guidelines and recommendations are based on expert opinion, single case reports, and small case series. Combining all of the published data in a patient-level analysis can provide a robust assessment of the influence of patient characteristics on survival with ECLS.
Objective:
To develop a prediction model of survival with good neurologic outcome for accidental hypothermia treated with ECLS.
Methods:
Electronic searches of PubMed, EMBASE, CINAHL were conducted with a hand search of reference lists and major surgical and critical care conference abstracts. Studies had to report the use of ECLS configured with a circuit, blood pump and oxygenator with an integrated heat exchanger. Randomized and observational studies were eligible for inclusion. Non-human, non-English and review manuscripts were deemed ineligible. Study authors were requested to submit patient level data when aggregate or incomplete individual patient data was provided in a study. Survival with good neurologic outcome was categorized for patients to last follow-up based on the reported scores on the Cerebral Performance Category (1 or 2), Glasgow Outcome Scale (4 or 5) and Pediatric Overall Performance Category (1 or 2). A one-stage, individual patient data meta-analysis was performed with a mixed-effects multi-level logistic regression model reporting odds ratio (OR) with a 95% confidence interval (CI).
Results:
Data from 44 observational studies and 40 case reports (n = 658) were combined and analyzed to identify independent predictors of survival with good neurologic outcome. The survival rate with good neurologic outcome of the entire cohort was 40.3% (265 of 658). ECLS rewarming rate (OR: 0.93; 95% CI: 0.88, 0.98; p = 0.007), female gender (OR: 2.78; 95% CI: 1.69, 4.58; p < 0.001), asphyxiation (OR: 0.19; 95% CI: 0.11, 0.35; p < 0.001) and serum potassium (OR: 0.62; 95% CI: 0.53, 0.73; p < 0.001) were associated with survival with a good neurologic outcome. The logistic regression model demonstrated excellent discrimination (c-statistic: 0.849; 95% CI: 0.823, 0.875).
Conclusions:
The use of extracorporeal life support in the treatment of hypothermic cardiac arrest provides a favourable chance of survival with good neurologic outcome. When used in a weighted scoring system, asphyxiation, serum potassium and gender can help clinicians prognosticate the benefit of resuscitating hypothermic patients with ECLS.
To improve our understanding of the evidence-based literature supporting temperaturemanagement during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.
Emergency medical services (EMS) personnel commonly use systolic blood pressure (sBP) to triage and treat acutely ill patients. The definition of prehospital hypotension and its associated outcomes are poorly defined. The authors sought to determine the discrimination of prehospital sBP thresholds for 30-day mortality and to compare patient classification by best-performing thresholds to traditional cutoffs.
In a community-based cohort of adult, nontrauma, noncardiac arrest patients transported by EMS between 2002 and 2006, entries to state hospital discharge data and death certificates were linked. Prehospital sBP thresholds between 40 and 140 mm Hg in derivation (n = 132,624) and validation (n = 22,020) cohorts and their discrimination for 30-day mortality, were examined. Cutoffs were evaluated using the 0/1 distance, Youden index, and adjusted Z-statistics from multivariable logistic regression models.
In the derivation cohort, 1,594 (1.2%) died within 24 hours, 7,404 (6%) were critically ill during hospitalization, and 6,888 (5%) died within 30 days. The area under the receiver operating characteristic (ROC) curve for sBP was 0.60 (95% confidence interval [CI] = 0.59, 0.61) for 30-day mortality and 0.64 (95% CI = 0.62 0.66) for 24-hour mortality. The 0/1 distance, Youden index, and adjusted Z-statistics found best-performing sBP thresholds between 110 and 120 mm Hg. When compared to an sBP ≤ 90 mm Hg, a cutoff of 110 mm Hg would identify 17% (n = 137) more deaths at 30 days, while overtriaging four times as many survivors.
Prehospital sBP is a modest discriminator of clinical outcomes, yet no threshold avoids substantial misclassification of 30-day mortality among noninjured patients.
ACCIDENTAL HYPOTHERMIA (I.E., AN INVOLUNTARY DROP IN CORE BODY temperature to <35°C [95°F]) is a condition associated with significant morbidity and mortality. Each year, approximately 1500 patients in the United States have hypothermia noted on their death certificate; however, the incidence of primary and secondary hypothermia and the associated morbidity and mortality remain unknown. In a single tertiary care center, 14 different rewarming methods were used to treat 84 cases of accidental hypothermia, which reflects the uncertainties about treatment and the potential for complications. Certain treatment approaches are available only in specialized centers, and clarification is needed regarding the choice between transporting a patient to a specialized center and providing treatment locally. Existing recommendations do not include recent developments in rewarming methods nor do they assist with decisions regarding transportation.
In addition to a number of very compelling clinical observations, an extensive body of extremely supportive experimental data has generated a very persuasive argument that intravenous estrogen should be routinely administered, as soon as possible, to all persons identified as having a critical illness or injury. Although, to date, definitive gold-standard clinical trials are lacking, what has made this provocative argument even more convincing is the longstanding, documented safety of intravenous estrogen for various illnesses and conditions as well as the relative ease and inexpensive cost of treatment. As such, even routine prehospital administration becomes extremely feasible for a myriad of conditions. More importantly, the worldwide magnitude of potential patients who could benefit is profound. Even if estrogen only changes the outcome in a relatively small percentage of applicable cases, the potential impact may still be of dramatic proportions in terms of the absolute number of lives saved and the resources spared worldwide. Resources may be spared not only in terms of diminishing the economic impact of death and long-term disability, but also in terms of preventing extended intensive care unit stays and treatment of preventable complications that result in longer recovery.
Patient rewarming after hypothermic cardiopulmonary bypass (CPB) has been linked to brain injury after cardiac surgery. In this study, we evaluated whether cooling and then rewarming of body temperature during CPB in adult patients is associated with alterations in cerebral blood flow (CBF)-blood pressure autoregulation.
One hundred twenty-seven adult patients undergoing CPB during cardiac surgery had transcranial Doppler monitoring of the right and left middle cerebral artery blood flow velocity. Eleven patients undergoing CPB who had arterial inflow maintained at >35 degrees C served as controls. The mean velocity index (Mx) was calculated as a moving, linear correlation coefficient between slow waves of middle cerebral artery blood flow velocity and mean arterial blood pressure. Intact CBF-blood pressure autoregulation is associated with an Mx that approaches 0. Impaired autoregulation results in an increasing Mx approaching 1.0. Comparisons of time-averaged Mx values were made between the following periods: before CPB (baseline), during the cooling and rewarming phases of CPB, and after CPB. The number of patients in each phase of CPB with an Mx >4.0, indicative of impaired CBF autoregulation, was determined.
During cooling, Mx (left, 0.29 +/- 0.18; right, 0.28 +/- 0.18 [mean +/- SD]) was greater than that at baseline (left, 0.17 +/- 0.21; right, 0.17 +/- 0.20; P <or= 0.0001). Mx increased during the rewarming phase of CPB (left, 0.40 +/- 0.19; right, 0.39 +/- 0.19) compared with baseline (P <or= 0.001) and the cooling phase (P <or= 0.0001), indicating impaired CBF autoregulation. After CPB, Mx (left, 0.27 +/- 0.20; right, 0.28 +/- 0.21) was higher than at baseline (left, P = 0.0004; right, P = 0.0003), no different than during the cooling phase, but lower than during rewarming (left, P <or= 0.0001; right, P <or= 0.0005). Forty-three patients (34%) had an Mx >or=0.4 during the cooling phase of CPB and 68 (53%) had an average Mx >or=0.4 during rewarming. Nine of the 11 warm controls had an average Mx >or=0.4 during the entire CPB period. There were 7 strokes and 1 TIA after surgery. All strokes were in patients with Mx >or= 0.4 during rewarming (P = 0.015). The unadjusted odds ratio for any neurologic event (stroke or transient ischemic attack) for patients with Mx >or= 0.4 during rewarming was 6.57 (95% confidence interval, 0.79 to 55.0, P < 0.08).
Hypothermic CPB is associated with abnormal CBF-blood pressure autoregulation that is worsened with rewarming. We found a high rate of strokes in patients with evidence of impaired CBF autoregulation. Whether a pressure-passive CBF state during rewarming is associated with risk for ischemic brain injury requires further investigation.
Multiple rewarming methods have been recommended for the treatment of hypothermia in the ED. Because the hypothermic patient population is heterogenous, a method for stratifying mortality risk when comparing therapies is desired. We used univariable and multivariable statistical analyses to identify variables which discriminated between patient death or survival in the 24 h after arrival in the ED. Prehospital cardiac arrest, a low or absent presenting BP, elevated BUN, and the need for either tracheal intubation or NG tube placement in the ED were found to be significant predictors of patient demise in a large database (n = 428). The likelihood ratio was used to develop and validate an empiric hypothermia outcome score that can be used in future hypothermia treatment studies to account for differences of patient presentation.
Methods of rewarming patients with severe accidental hypothermia remain controversial. This paper reports our experience with the use of forced air rewarming in patients with severe accidental hypothermia and a body core temperature below 30 degrees C. Fifteen hypothermic patients (body core temperature 24-30 degrees C) were successfully treated with forced air rewarming to a body core temperature above 35 degrees C (mean rewarming rate 1.7 degrees C/h, range from 0.7 to 3.4 degrees C/h). An afterdrop phenomenon was not observed in any of the patients. Nine hypothermic patients (group 1) had no prehospital cardiac arrest, all nine were long-term survivors and made a full recovery. Six patients (group 2) had prehospital cardio circulatory arrest with restoration of spontaneous circulation. None of the group 2 patients survived long-term. Group 1 and group 2 patients did not differ in core temperature (26.6+/-1.6 degrees C group 1 and 27.0+/-1.8 degrees C group 2). Group 2 patients needed catecholamine support during rewarming more frequently (83 versus 22%) and had higher lactate levels and lower pH values at all points of observation. In conclusion our preliminary data indicate that forced air rewarming is an efficient and safe method of managing patients with severe accidental hypothermia. The poor outcome of patients with a history of prehospital cardiopulmonary resuscitation is probably due to irreversible ischaemic brain damage in primarily asphyxiated avalanche and near-drowning victims, rather than the consequence of the rewarming method used.
Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery.
Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale.
Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment.
Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.
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Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and informed consent, 165 coronary artery bypass graft surgery patients were studied. Patients received similar surgical and anesthetic management until rewarming from hypothermic (28 degrees -32 degrees C) CPB. Group 1 (control; n = 100) was warmed in a conventional manner (4 degrees -6 degrees C gradient between nasopharyngeal and CPB perfusate temperature) whereas Group 2 (slow rewarm; n = 65) was warmed at a slower rate, maintaining no more than 2 degrees C difference between nasopharyngeal and CPB perfusate temperature. Neurocognitive function was assessed at baseline and 6 wk after coronary artery bypass graft surgery. Univariable analysis revealed no significant differences between the Control and Slow Rewarming groups in the stroke rate. Multivariable linear regression analysis, examining treatment group, diabetes, baseline cognitive function, and cross-clamp time revealed a significant association between change in cognitive function and rate of rewarming (P = 0.05).
Implications:
Slower rewarming during cardiopulmonary bypass (CPB) was associated with better cognitive performance at 6 wk. These results suggest that a slower rewarming rate with lower peak temperatures during CPB may be an important factor in the prevention of neurocognitive decline after hypothermic CPB.
Temperature is a well-known modulator of experimental cerebral injury. We hypothesized that hyperthermia would be associated with a worsened cognitive outcome after coronary artery bypass graft surgery (CABG).
Three hundred consenting patients undergoing cardiopulmonary bypass for CABG had hourly postoperative temperatures recorded. The degree of postoperative hyperthermia was determined by using the maximum temperature within the first 24 hours as well as by calculating the area under the curve for temperatures >37 degrees C. Patients underwent a battery of cognitive testing both before surgery and 6 weeks after surgery. By use of factor analysis, 4 cognitive domains (scores) were identified, and the mean of the 4 scores was used to calculate the cognitive index (CI). Cognitive change was calculated as the 6-week CI minus the baseline CI. Multivariable linear regression (controlling for age, baseline cognitive function, and temperature during cardiopulmonary bypass) was used to compare postoperative hyperthermia with the postoperative cognitive change.
The maximum temperature within the first 24 hours after CABG ranged from 37.2 degrees C to 39.3 degrees C. There was no relationship between area under the curve for temperatures >37 degrees C and cognitive dysfunction (P=0.45). However, the maximum postoperative temperature was associated with a greater amount of cognitive dysfunction at 6 weeks (P=0.05).
This is the first report relating postoperative hyperthermia to cognitive dysfunction after cardiac surgery. Whether the hyperthermia caused the worsened outcome or whether processes that resulted in the worsened cognitive outcome also produced hyperthermia requires further investigation. In addition, interventions to avoid postoperative hyperthermia may be warranted to improve cerebral outcome after cardiac surgery.
This article reviews past and present neuroprotective efforts and outlines a framework for the future development of techniques for neuroprotection during cardiac surgery.
Neurocognitive deficits occur frequently in patients undergoing cardiac surgery and may be caused, in part, by ischemic cerebral injury. Cerebral hypothermia has been proposed as a neuroprotective strategy to reduce ischemic injury in animal studies, in postcardiac arrest, and during cardiac surgery. We sought to evaluate the effects of sustained mild intraoperative hypothermia, without rewarming, on neurocognitive function after coronary artery bypass surgery.
Patients (aged >/= 60 years) undergoing non-urgent coronary surgery were randomized to an intraoperative nasopharyngeal temperature of 34 degrees C (hypothermic; n = 133) or 37 degrees C (normothermic; n = 134), maintained using water-circulating thermal control pads. No active rewarming was used. Transcranial Doppler was used intraoperatively to monitor middle cerebral artery emboli. Neuropsychometric testing, consisting of a battery of 16 tests, was performed by blinded observers preoperatively, before discharge, and at 3 months, and tests were divided into 4 cognitive domains. A deficit was prospectively defined as a 1 standard deviation decrease in individual scores from baseline in 1 or more domains.
The number of intraoperative cerebral emboli was similar between the control and the treated groups (188 [115-331] vs 182 [100-305], P = .71). At discharge, neurocognitive deficits were present in 45% of control patients and in 49% of treated patients (P = .49) and at 3 months decreased to 8% in control patients and 4% in treated patients (P = .28). There was no correlation between the total number of cerebral emboli and the occurrence of neurocognitive deficits (r = -0.01; P = .88). Hypothermic patients demonstrated trends toward reduced intensive care unit stay (1.4 +/- 1.0 days vs 1.2 +/- 0.7 days, P = .06) and increased chest tube output (655 +/- 327 mL/24 h vs 584 +/- 325 mL/24 h, P = .09).
Mild intraoperative hypothermia has no major adverse effects but does not decrease the incidence of neurocognitive deficits in patients undergoing coronary artery bypass surgery. In the absence of rewarming and cerebral hyperthermia, sustained mild hypothermia does not improve cognitive outcome.
Effects of mild cold shock (25
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