Targeted temperature management at 33°C versus 36°C after cardiac arrest.

BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. CONCLUSIONS: In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).

Bispectral index (BIS) helps predicting bad neurological outcome in comatose survivors after cardiac arrest and induced therapeutic hypothermia.

AIM OF THE STUDY: Determine the use of bispectral index (BIS) as prognostic tool in therapeutic hypothermia (TH) treated comatose survivors after cardiac arrest (CA), regardless of initial rhythm, location or cause. METHODS: Prospective, single-centre, unblinded, observational cohort study in an 18 bed general ICU in a tertiary teaching hospital. 45 consecutive comatose patients admitted after CA and treated with TH were included. All patients were sedated with a standardised protocol including neuromuscular blockade. Induced TH was started as soon as possible after arrival in the hospital and continued for 24h before slow rewarming. Sedation was stopped after reaching normothermia (36 degrees C). All patients benefited from maximal supportive intensive care and no therapeutic withdrawal or withholding was done unless bad neurological status was confirmed. Continuous BIS monitoring was performed over 72h in all patients. RESULTS: 14 patients presented BIS values of zero (0) during their ICU stay. At 6 months 11 patients were dead, 1 remained comatose and 2 had severe neurological sequelae (CPC3). No patient of this group had good neurological outcome or improved his neurological outcome between ICU and 6-month follow-up. 31 patients had BIS values higher than 0. At 6 months of those, 11 died, none remained comatose, 3 had bad neurological outcome (CPC3) and 17 had no or minor neurological sequelae (CPC1-2). Thus no correlation between good outcome and BIS values higher than 0 is possible. CONCLUSIONS: BIS values of 0 help predict bad neurological outcome after CA and induced hypothermia.

Late heartbeat-evoked potentials are associated with survival after cardiac arrest.

RATIONALE: Cardiac arrest (CA) is a serious condition characterized by high mortality rates, even after initial successful resuscitation, mainly due to neurological damage. Whether brain-heart communication is associated with outcome after CA is unknown. Heartbeat-evoked brain potentials (HEPs) represent neurophysiological indicators of brain-heart communication. The aim of this study was to address the association between HEPs and survival after CA. METHODS: HEPs were calculated from resting EEG/ECG in 55 CA patients 24 h after resuscitation. All patients were treated with targeted temperature management and a standardized sedation protocol during assessment. We investigated the association between HEP amplitude (180-320 ms, 455-595 ms, 860-1000 ms) and 6-month survival. RESULTS: Twenty-five of 55 patients (45%) were still alive at 6-month follow-up. Survivors showed a higher HEP amplitude at frontopolar and frontal electrodes in the late HEP interval than non-survivors. This effect remained significant after controlling for between-group differences in terms of age, Fentanyl dose, and time lag between resuscitation and EEG assessment. There were no group differences in heart rate or heart rate variability. CONCLUSION: Brain-heart communication, as reflected by HEPs, is associated with survival after CA. Future studies should address the brain-heart axis in CA.

Bispectral index to predict neurological outcome early after cardiac arrest.

AIM OF THE STUDY: To address the value of continuous monitoring of bispectral index (BIS) to predict neurological outcome after cardiac arrest. METHODS: In this prospective observational study in adult comatose patients treated by therapeutic hypothermia after cardiac arrest we measured bispectral index (BIS) during the first 24 hours of intensive care unit stay. A blinded neurological outcome assessment by cerebral performance category (CPC) was done 6 months after cardiac arrest. RESULTS: Forty-six patients (48%) had a good neurological outcome at 6-month, as defined by a cerebral performance category (CPC) 1-2, and 50 patients (52%) had a poor neurological outcome (CPC 3-5). Over the 24h of monitoring, mean BIS values over time were higher in the good outcome group (38 ± 9) compared to the poor outcome group (17 ± 12) (p<0.001). Analysis of BIS recorded every 30 minutes provided an optimal prediction after 12.5h, with an area under the receiver operating characteristic curve (AUC) of 0.89, a specificity of 89% and a sensitivity of 86% using a cut-off value of 23. With a specificity fixed at 100% (sensitivity 26%) the cut-off BIS value was 2.4 over the first 271 minutes. In multivariable analyses including clinical characteristics, mean BIS value over the first 12.5h was a predictor of neurological outcome (p = 6E-6) and provided a continuous net reclassification index of 1.28% (p = 4E-10) and an integrated discrimination improvement of 0.31 (p=1E-10). CONCLUSIONS: Mean BIS value calculated over the first 12.5h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest.

Assessment of procalcitonin to predict outcome in hypothermia-treated patients after cardiac arrest.

Objective. Determine the potential of procalcitonin (PCT) to predict neurological outcome after hypothermia treatment following cardiac arrest. Methods. Retrospective analysis of patient data over a 2-year period. Mortality and neurological outcome of survivors were determined 6 months after cardiac arrest using the Cerebral Performance Category (CPC) score. Results. Data from 53 consecutive patients were analyzed. Median age was 63 (54-71) and 79% were male. Twenty-seven patients had good outcome (CPC ≤ 2) whereas 26 had severe neurological sequelae or died (CPC 3-5). At 48 h, after regaining normothermia, PCT was significantly higher in patients with bad outcome compared to those with good outcome: 3.38 (1.10-24.48) versus 0.28 (0-0.75) ng/mL (P < 0.001). PCT values correlated with bad neurological outcome (r = 0.54, P = 0.00004) and predicted outcome with an area under the curve of 0.84 (95% CI 0.73-0.96). A cutoff point of 1 ng/mL provided a sensitivity of 85% and a specificity of 81%. Above a PCT level of 16 ng/mL, no patient regained consciousness. PCT provided an additive value over simplified acute physiology score II. Conclusions. PCT might be an ancillary marker for outcome prediction after cardiac arrest treated by induced hypothermia.