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Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

ABSTRACT: Mild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia.To determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia.A retrospective observational study of patients treated with therapeutic hypothermia after cardiac arrest from 2007 through 2014. Baseline demographic data and daily delirium assessments throughout the intensive care unit stay were obtained. The association between duration of delirium and various risk factors was assessed.Of 251 patients, 107 (43%) awoke from coma. Among the 107 survivors, all had at least 1 day of delirium during their intensive care unit stay. Median number of days of delirium was 4.0 (interquartile range, 2.0-7.5). Multivariable analysis revealed that age (odds ratio, 1.72; 95% CI, 1.0-2.95; P = .05), time from cardiopulmonary resuscitation to return of spontaneous circulation (odds ratio 1.52; 95% CI, 1.11-2.07; P = .01), and total dose of prewarming propofol (odds ratio, 0.02; 95% CI, 0.00-0.48; P = .02) were associated with duration of delirium.All survivors of cardiac arrest treated with mild therapeutic hypothermia had at least 1 day of delirium. Age and time from initiation of cardiopulmonary resuscitation to return of spontaneous circulation were associated with prolonged delirium, whereas exposure to propofol was protective against delirium. These findings are limited to this unique cohort and may not be generalizable to different populations.

SUBMITTER: Pollock JS

PROVIDER: S-EPMC5240926 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

Pollock Jeremy S JS Hollenbeck Ryan D RD Wang Li L Holmes Benjamin B Young Michael N MN Peters Matthew M Ely E Wesley EW McPherson John A JA Vasilevskis Eduard E EE

American journal of critical care : an official publication, American Association of Critical-Care Nurses 20160701 4

<h4>Background</h4>Mild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia.<h4>Objective</h4>To determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia.<h4>Methods</h4>A retrospective observational study of patients ...[more]

PMID: 27369041

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Project description:Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 +/- 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 +/- 1.3 microg/min [arrival intensive care unit (ICU) 35.4 degrees C] to 4.6 +/- 1.0 microg/min (34 degrees C) and 2.8 +/- 0.5 microg/min (33 degrees C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 +/- 1.7 bpm (arrival ICU) to 77.3 +/- 1.5 bpm (34 degrees C) and 70.3 +/- 1.4 bpm (33 degrees C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 +/- 23% at 27 degrees C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca(2+) content, but can be elicited even when the SR Ca(2+) release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca(2+) sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca(2+)-sensitivity.

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:BackgroundTherapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited.MethodsWe 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.ResultsA 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.ConclusionsIn 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:BackgroundSeparate 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.MethodsCombine 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.Results624 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.ConclusionsAnalysis 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.

Project description:ImportanceComatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures.ObjectiveTo determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest.Design, setting, and participantsSingle-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020.InterventionsPatients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours.Main outcomes and measuresThe primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit.ResultsAmong 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively.Conclusions and relevanceIn comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference.Trial registrationClinicalTrials.gov Identifier: NCT02011568.

Dataset Information

Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

Publications

Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

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