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Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

ABSTRACT: Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy.Prospective randomized laboratory investigation.University research laboratory.A total of 268 male Long Evans rats.Post-cardiac-arrest therapeutic hypothermia.Adult male Long Evans rats that achieved return of spontaneous circulation after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37°C ± 1°C) or therapeutic hypothermia (33°C ± 1°C) initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation and maintained for 24 or 48 hrs. Therapeutic hypothermia initiated 0, 1, 4, and 8 hrs after return of spontaneous circulation resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14%, respectively, compared to 17% for normothermic controls and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0%, respectively, compared to 2% for normothermic controls (*p < .05 vs. normothermia). These outcomes were not different when therapeutic hypothermia was maintained for 24 vs. 48 hrs. In contrast, hippocampal CA1 pyramidal neuron counts were 53% ± 27%*, 53% ± 19%*, 51% ± 24%*, and 65% ± 16%* of normal, respectively, when therapeutic hypothermia was initiated 0, 1, 4, or 8 hrs after return of spontaneous circulation compared to 9% in normothermic controls (*p < .01 vs. normothermia). Furthermore, surviving neuron counts were greater when therapeutic hypothermia was maintained for 48 hrs compared to 24 hrs (68% ± 15%* vs. 42% ± 22%, *p < .0001).In this study, post-cardiac-arrest therapeutic hypothermia resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4 hrs after return of spontaneous circulation. However, histologic assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when therapeutic hypothermia was maintained for 48 vs. 24 hrs.

SUBMITTER: Che D

PROVIDER: S-EPMC3102228 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

Che Dongfang D Li Luchuan L Kopil Catherine M CM Liu Ziyue Z Guo Wensheng W Neumar Robert W RW

Critical care medicine 20110601 6

<h4>Objective</h4>Post-cardiac-arrest therapeutic hypothermia improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac-arrest therapeutic hypothermia is dependent on the onset and duration of therapy.<h4>Design</h4>Prospective randomized laboratory investigation.<h4>Setting</h4>University research laboratory.<h4>Subjects</h4>A total of 268 male Long Evans rats.<h4>Interventions</h4>Post-cardiac-arrest therapeutic hypothermia.<h4>Me ...[more]

PMID: 21610611

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Project description:Therapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not exist, and comparative effectiveness data are limited.To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest.In this cohort study, within the national Get With the Guidelines-Resuscitation registry, 26?183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015.Induction of therapeutic hypothermia.The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests.Overall, 1568 of 26?183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5% male) were matched by propensity score to 3714 non-hypothermia-treated patients (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, -3.6% [95% CI, -6.3% to -0.9%]; P?=?.01), and this association was similar (interaction P?=?.74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76 to 0.99]; risk difference, -3.2% [95% CI, -6.2% to -0.3%]) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference, -4.6% [95% CI, -10.9% to 1.7%]). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% [246 of 1443 patients]; non-hypothermia-treated group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk difference, -4.4% [95% CI, -6.8% to -2.0%]; P?<?.001) and for both rhythm types (interaction P?=?.88).Among patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.

Project description:BACKGROUND:Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS:In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS:The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS:Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Project description:Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest.A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality.In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Project description:BACKGROUND:Separate trials to evaluate therapeutic hypothermia after paediatric cardiac arrest for out-of-hospital and in-hospital settings reported no statistically significant differences in survival with favourable neurobehavioral outcome or safety compared to therapeutic normothermia. However, larger sample sizes might detect smaller clinical effects. Our aim was to pool data from identically conducted trials to approximately double the sample size of the individual trials yielding greater statistical power to compare outcomes. METHODS:Combine individual patient data from two clinical trials set in forty-one paediatric intensive care units in USA, Canada and UK. Children aged at least 48?h up to 18 years old, who remained comatose after resuscitation, were randomized within 6?h of return of circulation to hypothermia or normothermia (target 33.0?°C or 36.8?°C). The primary outcome, survival 12 months post-arrest with Vineland Adaptive Behaviour Scales, Second Edition (VABS-II) score at least 70 (scored from 20 to 160, higher scores reflecting better function, population mean?=?100, SD?=?15), was evaluated among patients with pre-arrest scores ?70. RESULTS:624 patients were randomized. Among 517 with pre-arrest VABS-II scores ?70, the primary outcome did not significantly differ between hypothermia and normothermia groups (28% [75/271] and 26% [63/246], respectively; relative risk, 1.08; 95% confidence interval [CI], 0.81 to 1.42; p?=?0.61). Among 602 evaluable patients, the change in VABS-II score from baseline to 12 months did not differ significantly between groups (p?=?0.20), nor did, proportion of cases with declines no more than 15 points or improvement from baseline [22% (hypothermia) and 21% (normothermia)]. One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; relative risk, 1.15; 95% CI, 0.95 to 1.38; p?=?0.15). Incidences of blood-product use, infection, and serious cardiac arrhythmia adverse events, and 28-day mortality, did not differ between groups. CONCLUSIONS:Analysis of combined data from two paediatric cardiac arrest targeted temperature management trials including both in-hospital and out-of-hospital cases revealed that hypothermia, as compared with normothermia, did not confer a significant benefit in survival with favourable functional outcome at one year.

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Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

Publications

Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

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