Search

Background: Pre-intensive care unit (ICU) induction of targeted temperature management (TTM) with cold intravenous (i.v.) fluids does not appear to improve outcomes after in out-of-hospital cardiac arrest (OHCA). We hypothesized that this may be due to ineffective cooling and side effects. Methods: A post hoc analysis of a sub-group of patients (n = 352) in the TTH48 trial (NCT01689077) who received or did not receive pre-ICU cooling using cold i.v. fluids. Data collection included patient characteristics, cardiac arrest factors, cooling methods, side effects and continuous core temperature measurements. The primary endpoint was the time to target temperature (TTT, <34 °C), and the secondary endpoints included the incidence of circulatory side effects, abnormal electrolyte levels and hypoxia within the first 24 h of ICU care. A difference of 1 h in the TTT was determined as clinically significant a priori. Results: Of 352 patients included in the present analysis, 110 received pre-ICU cold fluids. The median time to the return of spontaneous circulation (ROSC) and TTT in the pre-ICU cold fluids group was longer than that of the group that did not receive pre-ICU cold fluids (318 vs. 281 min, p < 0.01). In a linear regression model including the treatment centre, body mass index (BMI), chronic heart failure, diabetes mellitus and time to ROSC, the use of pre-ICU cold i.v. fluids was not associated with a shorter time to the target temperature (standardized beta coefficient: 0.06, 95% CI for B -49 and 16, p = 0.32). According to the receipt or not of pre-ICU cold i.v. fluids, there was no difference in the proportion of patients with hypoxia on ICU admission (1.8% vs. 3.3%, p = 0.43) or the proportion of patients with electrolyte abnormalities (hyponatremia: 1.8% vs. 2.9% p = 0.54; hypokalaemia: 1.8% vs. 4.5%, p = 0.20). Furthermore, there was no difference in hospital mortality between the groups. Conclusions: The initiation of TTM with cold i.v. fluids befo

Background: Acute kidney injury (AKI) is common after cardiac arrest and targeted temperature management (TTM). The impact of different lengths of cooling on the development of AKI has not been well studied. In this study of patients included in a randomised controlled trial of TTM at 33 °C for 24 versus 48 h after cardiac arrest (TTH48 trial), we examined the influence of prolonged TTM on AKI and the incidence and factors associated with the development of AKI. We also examined the impact of AKI on survival. Methods: This study was a sub-study of the TTH48 trial, which included patients cooled to 33 ± 1 °C after out-of-hospital cardiac arrest for 24 versus 48 h. AKI was classified according to the KDIGO AKI criteria based on serum creatinine and urine output collected until ICU discharge for a maximum of seven days. Survival was followed for up to six months. The association of admission factors on AKI was analysed with multivariate analysis and the association of AKI on mortality was analysed with Cox regression using the time to AKI as a time-dependent covariate. Results: Of the 349 patients included in the study, 159 (45.5%) developed AKI. There was no significant difference in the incidence, severity or time to AKI between the 24- and 48-h groups. Serum creatinine values had significantly different trajectories for the two groups with a sharp rise occurring during rewarming. Age, time to return of spontaneous circulation, serum creatinine at admission and body mass index were independent predictors of AKI. Patients with AKI had a higher mortality than patients without AKI (hospital mortality 36.5% vs 12.5%, p < 0.001), but only AKI stages 2 and 3 were independently associated with mortality. Conclusions: We did not find any association between prolonged TTM at 33 °C and the risk of AKI during the first seven days in the ICU. AKI is prevalent after cardiac arrest and TTM and occurs in almost half of all ICU admitted patients and more commonly in the elderl

Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and t

IMPORTANCE: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. OBJECTIVE: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM. DESIGN, SETTING, AND PARTICIPANTS: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016. INTERVENTIONS: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C. MAIN OUTCOMES AND MEASURES: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. RESULTS: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. More patients in the 48-hour group had a favorable outcome, but this was not statistically significant. Six-month mortality was not different between the groups. Adverse events were more common in the 48-hour group than in the 24-hour group. There was no significant difference in the time to mortality (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). The median length of ICU stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group. (Table Presented) C, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (+/- 1) degrees C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (+/- 1) degrees C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest.

Background: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 +/- 1 degrees C for 48 hours compared to 24 hours results in a better long-term neurological outcome. Methods: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 +/- 1 degrees C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. Discussion: This is the first randomised trial to investigate the effect of the duration of TTM at 33 +/- 1 degrees C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients.

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (±1) °C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest. Trial registration: ClinicalTrials.gov: NCT01689077, 17 September 2012, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. Methods: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. Discussion: This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. Trial registration:NCT01689077, SCOPUS: ar.j, info:eu-repo/semantics/published