Hypothermia for neuroprotection in adults after cardiac arrest.

BACKGROUND: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical for a favourable prognosis. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016. OBJECTIVES: To evaluate the benefits and harms of therapeutic hypothermia after cardiac arrest in adults compared to standard treatment. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults comparing therapeutic hypothermia after cardiac arrest with standard treatment (control). We included studies with adults cooled by any method, applied within six hours of cardiac arrest, to target body temperatures of 32 °C to 34 °C. Good neurological outcome was defined as no or only minor brain damage allowing people to live an independent life. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. neurological recovery. Our secondary outcomes were 2. survival to hospital discharge, 3. quality of life, 4. cost-effectiveness and 5. ADVERSE EVENTS: We used GRADE to assess certainty. MAIN RESULTS: We found 12 studies with 3956 participants reporting the effects of therapeutic hypothermia on neurological outcome or survival. There were some concerns about the quality of all the studies, and two studies had high risk of bias overall. When we compared conventional cooling methods versus any type of standard treatment (including a body temperature of 36 °C), we found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.12 to 1.76; 11 studies, 3914 participants). The certainty of the evidence was low. When we compared therapeutic hypothermia with fever prevention or no cooling, we found that participants in the therapeutic hypothermia group were more likely to reach a favourable neurological outcome (RR 1.60, 95% CI 1.15 to 2.23; 8 studies, 2870 participants). The certainty of the evidence was low. When we compared therapeutic hypothermia methods with temperature management at 36 °C, there was no evidence of a difference between groups (RR 1.78, 95% CI 0.70 to 4.53; 3 studies; 1044 participants). The certainty of the evidence was low. Across all studies, the incidence of pneumonia, hypokalaemia and severe arrhythmia was increased amongst participants receiving therapeutic hypothermia (pneumonia: RR 1.09, 95% CI 1.00 to 1.18; 4 trials, 3634 participants; hypokalaemia: RR 1.38, 95% CI 1.03 to 1.84; 2 trials, 975 participants; severe arrhythmia: RR 1.40, 95% CI 1.19 to 1.64; 3 trials, 2163 participants). The certainty of the evidence was low (pneumonia, severe arrhythmia) to very low (hypokalaemia). There were no differences in other reported adverse events between groups. AUTHORS' CONCLUSIONS: Current evidence suggests that conventional cooling methods to induce therapeutic hypothermia may improve neurological outcomes after cardiac arrest. We obtained available evidence from studies in which the target temperature was 32 °C to 34 °C.

Predictors for Prehospital First-Pass Intubation Success in Germany.

(1) Background: Endotracheal intubation in the prehospital setting is an important skill for emergency physicians, paramedics, and other members of the EMS providing airway management. Its success determines complications and patient mortality. The aim of this study was to find predictors for first-pass intubation success in the prehospital emergency setting. (2) The study was based on a retrospective analysis of a population-based registry of prehospital advanced airway management in Germany. Cases of endotracheal intubation by the emergency medical services in the cities of Tübingen and Jena between 2016 and 2019 were included. The outcome of interest was first-pass intubation success. Univariate and multivariable regression analysis were used to analyse the influence of predefined predictors, including the characteristics of patients, the intubating staff, and the clinical situation. (3) Results: A total of 308 patients were analysed. After adjustment for multiple confounders, the direct vocal cord view, a less favourable Cormack-Lehane classification, the general practitioner as medical specialty, and location and type of EMS were independent predictors for first-pass intubation success. (4) Conclusions: In physician-led emergency medical services, the laryngoscopic view, medical specialty, type of EMS, and career level are associated with FPS. The latter points towards the importance of experience and regular training in endotracheal intubation.

Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback.

OBJECTIVE: The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32-34°C. DATA SOURCES: We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021. STUDY SELECTION: We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival. DATA EXTRACTION: We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions. DATA SYNTHESIS: A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49-0.74) and survival (OR, 0.8; 95% CI, 0.66-0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF. CONCLUSIONS: Our results suggest that in patients resuscitated from CA and treated with TTM at 32-34°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.

Targeted temperature management after cardiac arrest. A systematic review and meta-analysis of animal studies.

AIM: Animal studies are an important knowledge base when information from clinical trials is missing or conflicting. The goal of this systematic review and meta-analysis was to investigate the effect of conventional targeted temperature management (TTM) between 32-36 °C in animal cardiac arrest models, and to estimate the influence of effect modifiers on the pooled effect of TTM. DATA SOURCES: We searched Medline and Scopus from inception to May 2020 for randomised controlled animal trials assessing the effect of conventional TTM versus normothermia on neurologic outcome after cardiac arrest. We extracted data on study characteristics, study quality data, neurologic outcome, mortality, and potential effect modifiers. RESULTS: We retrieved 1635 studies, 45 studies comprising data of 981 animals met the inclusion criteria. Risk of bias was high in 17 studies and moderate in 28 studies. We undertook random-effects meta-analyses and meta-regression analyses to calculate the pooled effect and the influence of effect modifiers. There was a strong beneficial effect of TTM as compared to normothermia on neurologic outcome (standardised mean difference of 1.4 [95% CI -1.7 to -1.1; I2 = 75%]). Faster cooling rates, lower target temperature of TTM within the range of 32-36 °C, and shorter duration of cooling were independently associated with an increasing effect size of TTM. CONCLUSIONS: This systematic review of animal cardiac arrest studies showed a consistent favourable effect of postresuscitation TTM as compared to normothermia on neurologic outcome that increased with lower target temperatures.

Systematic review and meta-analysis of intravascular temperature management vs. surface cooling in comatose patients resuscitated from cardiac arrest.

OBJECTIVE: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) vs. surface cooling methods (SCM) for induced hypothermia (IH). METHODS: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods. ELIGIBILITY: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM vs. SCM were eligible for inclusion. RESULTS: In total, 12 studies met inclusion criteria. These enrolled 1573 patients who received IVTM; and 4008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI -1%, 5%)]. Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM vs. SCM. There was no significant difference in other evaluated adverse events between groups. CONCLUSIONS: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest.

Airway physical examination tests for detection of difficult airway management in apparently normal adult patients.

BACKGROUND: The unanticipated difficult airway is a potentially life-threatening event during anaesthesia or acute conditions. An unsuccessfully managed upper airway is associated with serious morbidity and mortality. Several bedside screening tests are used in clinical practice to identify those at high risk of difficult airway. Their accuracy and benefit however, remains unclear. OBJECTIVES: The objective of this review was to characterize and compare the diagnostic accuracy of the Mallampati classification and other commonly used airway examination tests for assessing the physical status of the airway in adult patients with no apparent anatomical airway abnormalities. We performed this individually for each of the four descriptors of the difficult airway: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation. SEARCH METHODS: We searched major electronic databases including CENTRAL, MEDLINE, Embase, ISI Web of Science, CINAHL, as well as regional, subject specific, and dissertation and theses databases from inception to 16 December 2016, without language restrictions. In addition, we searched the Science Citation Index and checked the references of all the relevant studies. We also handsearched selected journals, conference proceedings, and relevant guidelines. We updated this search in March 2018, but we have not yet incorporated these results. SELECTION CRITERIA: We considered full-text diagnostic test accuracy studies of any individual index test, or a combination of tests, against a reference standard. Participants were adults without obvious airway abnormalities, who were having laryngoscopy performed with a standard laryngoscope and the trachea intubated with a standard tracheal tube. Index tests included the Mallampati test, modified Mallampati test, Wilson risk score, thyromental distance, sternomental distance, mouth opening test, upper lip bite test, or any combination of these. The target condition was difficult airway, with one of the following reference standards: difficult face mask ventilation, difficult laryngoscopy, difficult tracheal intubation, and failed intubation. DATA COLLECTION AND ANALYSIS: We performed screening and selection of the studies, data extraction and assessment of methodological quality (using QUADAS-2) independently and in duplicate. We designed a Microsoft Access database for data collection and used Review Manager 5 and R for data analysis. For each index test and each reference standard, we assessed sensitivity and specificity. We produced forest plots and summary receiver operating characteristic (ROC) plots to summarize the data. Where possible, we performed meta-analyses to calculate pooled estimates and compare test accuracy indirectly using bivariate models. We investigated heterogeneity and performed sensitivity analyses. MAIN RESULTS: We included 133 (127 cohort type and 6 case-control) studies involving 844,206 participants. We evaluated a total of seven different prespecified index tests in the 133 studies, as well as 69 non-prespecified, and 32 combinations. For the prespecified index tests, we found six studies for the Mallampati test, 105 for the modified Mallampati test, six for the Wilson risk score, 52 for thyromental distance, 18 for sternomental distance, 34 for the mouth opening test, and 30 for the upper lip bite test. Difficult face mask ventilation was the reference standard in seven studies, difficult laryngoscopy in 92 studies, difficult tracheal intubation in 50 studies, and failed intubation in two studies. Across all studies, we judged the risk of bias to be variable for the different domains; we mostly observed low risk of bias for patient selection, flow and timing, and unclear risk of bias for reference standard and index test. Applicability concerns were generally low for all domains. For difficult laryngoscopy, the summary sensitivity ranged from 0.22 (95% confidence interval (CI) 0.13 to 0.33; mouth opening test) to 0.67 (95% CI 0.45 to 0.83; upper lip bite test) and the summary specificity ranged from 0.80 (95% CI 0.74 to 0.85; modified Mallampati test) to 0.95 (95% CI 0.88 to 0.98; Wilson risk score). The upper lip bite test for diagnosing difficult laryngoscopy provided the highest sensitivity compared to the other tests (P < 0.001). For difficult tracheal intubation, summary sensitivity ranged from 0.24 (95% CI 0.12 to 0.43; thyromental distance) to 0.51 (95% CI 0.40 to 0.61; modified Mallampati test) and the summary specificity ranged from 0.87 (95% CI 0.82 to 0.91; modified Mallampati test) to 0.93 (0.87 to 0.96; mouth opening test). The modified Mallampati test had the highest sensitivity for diagnosing difficult tracheal intubation compared to the other tests (P < 0.001). For difficult face mask ventilation, we could only estimate summary sensitivity (0.17, 95% CI 0.06 to 0.39) and specificity (0.90, 95% CI 0.81 to 0.95) for the modified Mallampati test. AUTHORS' CONCLUSIONS: Bedside airway examination tests, for assessing the physical status of the airway in adults with no apparent anatomical airway abnormalities, are designed as screening tests. Screening tests are expected to have high sensitivities. We found that all investigated index tests had relatively low sensitivities with high variability. In contrast, specificities were consistently and markedly higher than sensitivities across all tests. The standard bedside airway examination tests should be interpreted with caution, as they do not appear to be good screening tests. Among the tests we examined, the upper lip bite test showed the most favourable diagnostic test accuracy properties. Given the paucity of available data, future research is needed to develop tests with high sensitivities to make them useful, and to consider their use for screening difficult face mask ventilation and failed intubation. The 27 studies in 'Studies awaiting classification' may alter the conclusions of the review, once we have assessed them.

Pre-hospital versus in-hospital initiation of cooling for survival and neuroprotection after out-of-hospital cardiac arrest.

BACKGROUND: Targeted temperature management (also known under 'therapeutic hypothermia', 'induced hypothermia'", or 'cooling') has been shown to be beneficial for neurological outcome in patients who have had successful resuscitation from sudden cardiac arrest, but it remains unclear when this intervention should be initiated. OBJECTIVES: To assess the effects of pre-hospital initiation of cooling on survival and neurological outcome in comparison to in-hospital initiation of cooling for adults with pre-hospital cardiac arrest. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, BIOSIS, and three trials registers from inception to 5 March 2015, and carried out reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) in adults with out-of-hospital cardiac arrest comparing cooling in the pre-hospital setting to in-hospital cooling. Our primary outcomes were survival and neurological outcome; our secondary outcomes were adverse events, quality of life, and length of stay in the intensive care unit (ICU) and in the hospital. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. MAIN RESULTS: We included seven RCTs (2369 participants randomized) on the induction of pre-hospital cooling in comparison to in-hospital cooling. There was considerable methodological heterogeneity and risk of bias mainly due to deficits in the administration of cooling, therefore we refrained from pooling the results for survival and neurological outcome and we presented the results for each study separately. Adverse events were rare: based on four studies with 1713 adults pre-hospital induction of cooling may increase the risk of cardiac re-arrests. Risk of bias within the seven individual studies was generally moderate. Overall the quality of the evidence was very low. This was mainly driven by inconsistency and low precision. AUTHORS' CONCLUSIONS: Currently, there is no convincing evidence to clearly delineate beneficial or harmful effects of pre-hospital induction of cooling in comparison to in-hospital induction of cooling. This conclusion is based on very low quality evidence.

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016. OBJECTIVES: We aimed to perform a systematic review and meta-analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta-analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia - five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia). AUTHORS' CONCLUSIONS: Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in-hospital cardiac arrest, asystole or non-cardiac causes of arrest.

Vasopressors for hypotensive shock.

BACKGROUND: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016. OBJECTIVES: Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data. MAIN RESULTS: We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion.

Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included. RESULTS: In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke. CONCLUSIONS: DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes. CLINICAL TRIAL REGISTRATION URL: http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.

Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

BACKGROUND: Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. This review was originally published in 2009. OBJECTIVES: We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcomes. We aimed to perform individual patient data analysis, if data were available, and to form subgroups according to the cardiac arrest situation. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2001, Issue 7); MEDLINE (1971 to July 2011); EMBASE (1987 to July 2011); CINAHL (1988 to July 2011); PASCAL (2000 to July 2011); and BIOSIS (1989 to July 2011). The original search was performed in January 2007. SELECTION CRITERIA: We included all randomized controlled trials assessing the effectiveness of therapeutic hypothermia in patients after cardiac arrest, without language restrictions. Studies were restricted to adult populations cooled with any cooling method, applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: Validity measures, the intervention, outcomes and additional baseline variables were entered into a database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies, individual patient data were available. MAIN RESULTS: We included four trials and one abstract reporting on 481 patients in the systematic review. The updated search resulted in no new studies to include. Quality of the included studies was good in three out of five studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods, patients in the hypothermia group were more likely to reach a best cerebral performance categories (CPC) score of one or two (five point scale: 1 = good cerebral performance, to 5 = brain death) during the hospital stay (individual patient data; RR 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies, there was no significant difference in reported adverse events between hypothermia and control. AUTHORS' CONCLUSIONS: Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.

Total epinephrine dose during asystole and pulseless electrical activity cardiac arrests is associated with unfavourable functional outcome and increased in-hospital mortality.

AIM: Epinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavourable outcome after ventricular fibrillation cardiac arrest in humans. Our objective was to investigate the association between the cumulative dose of epinephrine applied during resuscitation and unfavourable functional outcome and in-hospital mortality, in patients with asystole and pulseless electric activity. METHODS: Data on 946 patients admitted to the emergency department after resuscitation of witnessed in-hospital and out-of hospital cardiac arrest with asystole or pulseless electric activity were retrieved from the cardiac arrest registry of the emergency department at the Vienna General Hospital/Medical University of Vienna. Data were documented according to Utstein Style. The risk factor was cumulative epinephrine categorized into quartiles. The endpoints were unfavourable functional outcome and in-hospital mortality. RESULTS: The median cumulative amount of epinephrine administered was 2mg (IQR 0-5), ranging from 1 to 50mg. Of all patients 643/946 (68%) had an unfavourable functional outcome, 649/946 (69%) died during hospital stay. The multivariable analysis showed a statistically significant increasing risk for unfavourable functional outcome and in-hospital mortality outcome with increasing cumulative doses of epinephrine (unfavourable functional outcome: OR 1-1.45-2.25-2.95 over quartiles of epinephrine; in hospital mortality: OR 1-1.35-2.15-2.82 over quartiles of epinephrine). CONCLUSION: Our results show that an increasing cumulative dose of epinephrine during resuscitation of patients with asystole and pulseless electric activity is an independent risk factor for unfavourable functional outcome and in-hospital mortality.

The beneficial effect of mild therapeutic hypothermia depends on the time of complete circulatory standstill in patients with cardiac arrest.

AIM: Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min. METHODS: In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of 'no-flow' time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. 'No-flow' time was categorized into time quartiles (0, 1-2, 3-8, >8 min). RESULTS: One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14-1.93) this effect varies with 'no-flow' time. The effect is significant in patients with 'no-flow' times of more than 2 min (OR: 2.72; CI: 1.35-5.48) with the maximum benefit in those with 'no-flow' times beyond 8 min (OR: 6.15; CI: 2.23-16.99). CONCLUSION: The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.

Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms.

AIM: Mild therapeutic hypothermia (32-34°C) improves neurological recovery and reduces the risk of death in comatose survivors of cardiac arrest when the initial rhythm is ventricular fibrillation or pulseless ventricular tachycardia. The aim of the presented study was to investigate the effect of mild therapeutic hypothermia (32-34°C for 24h) on neurological outcome and mortality in patients who had been successfully resuscitated from non-ventricular fibrillation cardiac arrest. METHODS: In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm. Data were collected from 1992 to 2009. Main outcome measures were neurological outcome within six month and mortality after six months. RESULTS: Three hundred and seventy-four patients were analysed. Hypothermia was induced in 135 patients. Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes in comparison to patients who were not treated with hypothermia with an odds ratio of 1.84 (95% confidence interval: 1.08-3.13). In addition, the rate of mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34-0.93). CONCLUSION: Treatment with mild therapeutic hypothermia at a temperature of 32-34°C for 24h is associated with improved neurological outcome and a reduced risk of death following out-of-hospital cardiac arrest with non-shockable rhythms.

Vasopressors for hypotensive shock.

BACKGROUND: Initial goal directed resuscitation for shock usually includes the administration of intravenous fluids, followed by initiating vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics their effect on patient relevant outcomes remains controversial. This review was originally published in 2004 and was updated in 2011. OBJECTIVES: Our primary objective was to assess whether particular vasopressors reduce overall mortality, morbidity, and health-related quality of life. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS, and PsycINFO (from inception to March 2010). The original search was performed in November 2003. We also asked experts in the field and searched meta-registries for ongoing trials. SELECTION CRITERIA: Randomized controlled trials comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two authors abstracted data independently. Disagreement between the authors was discussed and resolved with a third author. We used a random-effects model for combining quantitative data. MAIN RESULTS: We identified 23 randomized controlled trials involving 3212 patients, with 1629 mortality outcomes. Six different vasopressors, alone or in combination, were studied in 11 different comparisons.All 23 studies reported mortality outcomes; length of stay was reported in nine studies. Other morbidity outcomes were reported in a variable and heterogeneous way. No data were available on quality of life or anxiety and depression outcomes. We classified 10 studies as being at low risk of bias for the primary outcome mortality; only four studies fulfilled all trial quality items.In summary, there was no difference in mortality in any of the comparisons between different vasopressors or combinations. More arrhythmias were observed in patients treated with dopamine compared to norepinephrine. Norepinephrine versus dopamine, as the largest comparison in 1400 patients from six trials, yielded almost equivalence (RR 0.95, 95% confidence interval 0.87 to 1.03). Vasopressors used as add-on therapy in comparison to placebo were not effective either. These findings were consistent among the few large studies as well as in studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: There is some evidence of no difference in mortality between norepinephrine and dopamine. Dopamine appeared to increase the risk for arrhythmia. There is not sufficient evidence of any difference between any of the six vasopressors examined. Probably the choice of vasopressors in patients with shock does not influence the outcome, rather than any vasoactive effect per se. There is not sufficient evidence that any one of the investigated vasopressors is clearly superior over others.

Cardiac arrest survivors with moderate elevated body mass index may have a better neurological outcome: a cohort study.

AIM: Body mass index (BMI) may influence the quality of cardiopulmonary resuscitation and may influence prognosis after cardiac arrest. To review the direct effect of obesity on outcome after cardiac arrest, the following cohort study was conducted. METHODS: This study based on a cardiac arrest registry comprising all adult patients with cardiac arrest of non-traumatic origin and restoration of spontaneous circulation (ROSC) admitted to the department of emergency medicine of a tertiary-care facility. Data were collected between January 1992 and December 2007 according to the Utstein criteria. We assessed the association between BMI according to the WHO classification (underweight, BMI<18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese ≥ 30), six-month survival and neurological recovery. RESULTS: Analysis was carried out on a total of 1915 adult patients (32% female). Patients had a median age of 59 years (interquartile range [IQR] 49-70) and a median BMI of 26.0 (IQR 23.9-29.1). Survival to six months was 50%. There was no significant difference in survival between the BMI groups (underweight 46%, normal weight 47%, overweight 52%, obese 51%). In a multivariate analysis neurological outcome was better in overweight patients as compared to subjects with normal BMI (odds ratio 1.35; 95% confidence interval 1.02-1.79). CONCLUSION: Body mass index may have no direct influence on six-month survival after cardiac arrest, but patients with moderately elevated BMI may have a better neurological prognosis.