practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management a substudy of the targeted temperature management trial

Aims: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings. Methods: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. Results: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4–8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH2O (6.4–8.7) and mean driving pressure was 14.6 cmH2O (±4.3). The median FiO2 fraction was 0.35 (0.30–0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO2 levels and respiratory minute volume were similar between groups. Conclusions: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO2 levels and a higher alveolar dead space fraction compared to TTTM36

Out-of-hospital cardiac arrest at place of residence is associated with worse outcomes in patients admitted to intensive care : a post-hoc analysis of the Targeted Temperature Management trial

BACKGROUND: The majority of out-of-hospital cardiac arrests (OHCAs) occur at place residence, which is associated with worse outcomes in unselected prehospital populations. Our aim was to investigate whether location of arrest was associated with outcome in a selected group of initial survivors admitted to intensive care.METHODS: This is a post-hoc analysis of the Targeted Temperature Management after cardiac arrest trial (TTM trial), a multicenter controlled trial, randomizing 950 OHCA patients to an intervention of 33°C or 36°C. The location of cardiac arrest was defined as place of residence vs. public place or other. The outcome measures were mortality and neurological outcome, as defined by the Cerebral Performance Category scale, at 180 days.RESULTS: Approximately half of 938 included patients arrested at place of residence (53%). Location groups did not differ with respect to age (p=0.11) or witnessed arrests (p=0.48) but bystander CPR was less common (p=0.02) at place of residence. OHCA at place of residence was associated with higher 180-day mortality, 55% vs. 38% (p<0.001) and worse neurological outcome, 61% vs. 43% (p<0.001) compared with a public place or other. After adjusting for known confounders, OHCA at place of residence remained an independent predictor of mortality (p=0.007).CONCLUSIONS: Half of all initial survivors after OHCA admitted to intensive care had an at place of residence which was independently associated with poor outcomes. Actions improve outcomes after OHCA at place of residence should be addressed in future trials

Head computed tomography for prognostication of poor outcome in comatose patients after cardiac arrest and targeted temperature management

INTRODUCTION: A multimodal approach to prognostication of outcome after cardiac arrest (CA) is recommended. Evidence for combinations of methods is low. In this post-hoc analysis we described findings on head computed tomography (CT) after CA. We also examined whether generalised oedema on CT alone or together with the biomarker Neuron-specific enolase (NSE) could predict poor outcome.METHODS: Patients participating in the Target Temperature Management after out-of-hospital-cardiac-arrest-trial underwent CT based on clinical indications. Findings were divided into pre-specified categories according to local radiologists descriptions. Generalised oedema alone and in combination with peak NSE at either 48h or 72h was correlated with poor outcome at 6 months follow-up using the Cerebral Performance Category (CPC 3-5).RESULTS: 356/939 (37.9%) of patients underwent head CT. Initial CT≤24h after CA was normal in 174/218 (79.8%), whilst generalised oedema was diagnosed in 21/218 (9.6%). Between days 1-7, generalised oedema was seen in 65/143 (45.5%), acute/subacute infarction in 27/143 (18.9%) and bleeding in 9/143 (6.3%). Overall, generalised oedema predicted poor outcome with 33.6% sensitivity (95%CI:28.1-39.5) and 98.4% specificity (95%CI:94.3-99.6), whilst peak NSE demonstrated sensitivities of 61.5-64.8% and specificity 95.7% (95%CI:89.5-98.4). The combination of peak NSE>38ng/l and generalised oedema on CT predicted poor outcome with 46.0% sensitivity (95%CI:36.5-55.8) with no false positives. NSE was significantly higher in patients with generalised oedema.CONCLUSION: In this study, generalised oedema was more common >24h≤7d after CA. The combination of CT and NSE improved sensitivity and specificity compared to CT alone, with no false positives in this limited population

Protocol-driven neurological prognostication and withdrawal of life-sustaining therapy after cardiac arrest and targeted temperature management

Background Brain injury is reportedly the main cause of death for patients resuscitated after out-of-hospital cardiac arrest (OHCA). However, the majority may actually die following withdrawal of life-sustaining therapy (WLST) with a presumption of poor neurological recovery. We investigated how the protocol for neurological prognostication was used and how related treatment recommendations might have affected WLST decision-making and outcome after OHCA in the targeted temperature management (TTM) trial. Methods Analyses of prospectively recorded data: details of neurological prognostication; recommended level-of-care; WLST decisions; presumed cause of death; and cerebral performance category (CPC) 6 months following randomization. Results Of 939 patients, 452 (48%) woke and 139 (15%) died, mostly for non-neurological reasons, before a scheduled time point for neurological prognostication (72 h after the end of TTM). Three hundred and thirteen (33%) unconscious patients underwent prognostication at a median 117 (IQR 93–137) hours after arrest. Thirty-three (3%) unconscious patients were not neurologically prognosticated and for 2 patients (1%) data were missing. Related care recommendations were: continue in 117 (37%); not escalate in 55 (18%); and withdraw in 141 (45%). WLST eventually occurred in 196 (63%) at median day 6 (IQR 5–8). At 6 months, only 2 patients with WLST were alive and 248 (79%) of prognosticated patients had died. There were significant differences in time to WLST and death after the different recommendations (log rank <0.001). Conclusion Delayed prognostication was relevant for a minority of patients and related to subsequent decisions on level-of-care with effects on ICU length-of-stay, survival time and outcome

Circulating Levels of miR-574-5p Are Associated with Neurological Outcome after Cardiac Arrest in Women : A Target Temperature Management (TTM) Trial Substudy

Purpose: Postresuscitation neuroprognostication is guided by neurophysiological tests, biomarker measurement, and clinical examination. Recent investigations suggest that circulating microRNAs (miRNA) may help in outcome prediction after cardiac arrest. We assessed the ability of miR-574-5p to predict neurological outcome after cardiac arrest, in a sex-specific manner. Methods: In this substudy of the Target Temperature Management (TTM) Trial, we enrolled 590 cardiac arrest patients for which blood samples were available. Expression levels of miR-574-5p were measured by quantitative PCR in plasma samples collected 48 h after cardiac arrest. The endpoint of the study was poor neurological outcome at 6 months (cerebral performance category scores 3 to 5). Results: Eighty-one percent of patients were men, and 49% had a poor neurological outcome. Circulating levels of miR-574-5p at 48 h were higher in patients with a poor neurological outcome at 6 months (p < 0.001), both in women and in men. Circulating levels of miR-574-5p were univariate predictors of neurological outcome (odds ratio (OR) [95% confidence interval (CI)]: 1.5 [1.26-1.78]). After adjustment with clinical variables and NSE, circulating levels of miR-574-5p predicted neurological outcome in women (OR [95% CI]: 1.9 [1.09-3.45]), but not in men (OR [95% CI]: 1.0 [0.74-1.28]). Conclusion: miR-574-5p is associated with neurological outcome after cardiac arrest in women

Incremental value of circulating MiR-122-5P to predict outcome after out of hospital cardiac arrest

Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p < 0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest

Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 °C and 36 °C

Background: We aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100. Methods: This is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 months was assessed using the Cerebral Performance Categories Scale (CPC 1-2 = good outcome, CPC 3-5 = poor outcome). Results: We included 687 patients from 29 sites in Europe. Median S100 values were higher in patients with a poor outcome at 24, 48, and 72 h: 0.19 (IQR 0.10-0.49) versus 0.08 (IQR 0.06-0.11) μg/ml, 0.16 (IQR 0.10-0.44) versus 0.07 (IQR 0.06-0.11) μg/L, and 0.13 (IQR 0.08-0.26) versus 0.06 (IQR 0.05-0.09) μg/L (p < 0.001), respectively. The ability to predict outcome was best at 24 h with an AUC of 0.80 (95% CI 0.77-0.83). S100 values were higher at 24 and 72 h in the 33 °C group than in the 36 °C group (0.12 [0.07-0.22] versus 0.10 [0.07-0.21] μg/L and 0.09 [0.06-0.17] versus 0.08 [0.05-0.10], respectively) (p < 0.02). In multivariable analyses including baseline variables and the allocated target temperature, the addition of S100 improved the AUC from 0.80 to 0.84 (95% CI 0.81-0.87) (p < 0.001), but S100 was not an independent outcome predictor. Adding S100 to the same model including neuron-specific enolase (NSE) did not further improve the AUC. Conclusions: The allocated target temperature did not affect S100 to a clinically relevant degree. High S100 values are predictive of poor outcome but do not add value to present prognostication models with or without NSE. S100 measured at 24 h and afterward is of limited value in clinical outcome prediction after OHCA. Trial registration: ClinicalTrials.gov identifier: NCT01020916. Registered on 25 November 2009

Targeted temperature management at 33\ub0C versus 36\ub0C after cardiac arrest.

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\ub0C or 36\ub0C. 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\ub0C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36\ub0C group (225 of 466 patients) (hazard ratio with a temperature of 33\ub0C, 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\ub0C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36\ub0C 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\ub0C did not confer a benefit as compared with a targeted temperature of 36\ub0C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)

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 degrees C or 36 degrees 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 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees 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 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees 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 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)