Nawaf Al-Subaie

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.).

Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design

BACKGROUND Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. METHODS The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. DISCUSSION The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.

Minimally invasive cardiac output monitoring.

Purpose of reviewThe measurement of cardiac output in the critically ill constitutes a vital part in the management of these patients. Minimally invasive techniques are gaining popularity as they allow continuous cardiac output monitoring while avoiding the risks associated with pulmonary artery catheterization. This article focuses on some of the commonly used minimally invasive devices that rely on pulse contour waveform analysis. Recent findingsThe current studies in the literature that assess the validity and the clinical applications of calibrated and noncalibrated arterial waveform derived cardiac output devices are discussed. SummaryThe minimally invasive cardiac output monitoring devices available differ in their methodology and application. Currently there is conflicting evidence as to the accuracy of some of these systems and further investigation into their clinical application is required.

Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and meta-analysis

AIM The prediction of return of spontaneous circulation (ROSC) during resuscitation of patients suffering of cardiac arrest (CA) is particularly challenging. Regional cerebral oxygen saturation (rSO2) monitoring through near-infrared spectrometry is feasible during CA and could provide guidance during resuscitation. METHODS We conducted a systematic review and meta-analysis on the value of rSO2 in predicting ROSC both after in-hospital (IH) or out-of-hospital (OH) CA. Our search included MEDLINE (PubMed) and EMBASE, from inception until April 4th, 2015. We included studies reporting values of rSO2 at the beginning of and/or during resuscitation, according to the achievement of ROSC. RESULTS A total of nine studies with 315 patients (119 achieving ROSC, 37.7%) were included in the meta-analysis. The majority of those patients had an OHCA (n=225, 71.5%; IHCA: n=90, 28.5%). There was a significant association between higher values of rSO2 and ROSC, both in the overall calculation (standardized mean difference, SMD -1.03; 95%CI -1.39,-0.67; p<0.001), and in the subgroups analyses (rSO2 at the beginning of resuscitation: SMD -0.79; 95%CI -1.29,-0.30; p=0.002; averaged rSO2 value during resuscitation: SMD -1.28; 95%CI -1.74,-0.83; p<0.001). CONCLUSIONS Higher initial and average regional cerebral oxygen saturation values are both associated with greater chances of achieving ROSC in patients suffering of CA. A note of caution should be made in interpreting these results due to the small number of patients and the heterogeneity in study design: larger studies are needed to clinically validate cut-offs for guiding cardiopulmonary resuscitation.

Long-Term Consequences of Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES To determine the effect of acute kidney injury (AKI) associated with cardiac surgery on long-term mortality. DESIGN Systematic review and meta-analysis of 9 observational studies extracted from the MEDLINE and EMBASE electronic databases. SETTING Hospitals undertaking cardiac surgery. PARTICIPANTS The study included 35,021 cardiac surgery patients from 9 observational studies. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Nine studies including 35,021 patients reported incidence of AKI data. The median incidence of AKI was 27.75% (IQR, 16.3%-38.86%). There was significant variation in the reported incidence (range, 11.97%-54%), which can be explained by the different AKI definitions used in the included studies. Eight studies provided adjusted effect size data with 95% confidence intervals on the impact of the occurrence of postoperative AKI and long-term mortality outcomes. Occurrence of postoperative AKI is associated with a significantly increased risk of long-term mortality (HR, 1.68; 95% CI, 1.45-1.95; p<0.00001). Recovery of renal function before hospital discharge is associated with a lower long-term mortality risk (HR, 1.31; 95% CI, 1.16-1.47; p<0.00001) compared with patients who experienced persistent abnormal renal function on hospital discharge (HR, 2.71; 95% CI, 1.26-5.82; p = 0.01). CONCLUSIONS There is wide variation in the reported incidence of AKI after cardiac surgery, reflecting the different AKI classification systems used. AKI after cardiac surgery is associated with an increased risk of long-term mortality. Patients with persistent renal dysfunction after hospital discharge carry a higher risk of AKI.

Cooling Techniques for Targeted Temperature Management Post-cardiac Arrest

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Haemodynamic monitoring in acute heart failure.

Acute Heart Failure is a major cause of hospitalisation, with a rate of death and complications. New guidelines have been developed in order to diagnose and treat this disease. Despite these efforts pathophysiology and treatments options are still limited. There is agreement among the experts that increasing the cardiac output and the stroke volume without fluid overloading the patient should be the goal of every treatment. Despite this, there is no agreement on how to monitor the cardiac function and how to follow it after a therapeutic intervention. In other fields of critical care cardiovascular monitoring and application of early goal directed protocols showed benefits. This review explores the available possibilities of how to monitor the cardiac function in Acute Heart Failure. Standard and more advanced techniques are presented. Cardiac output monitors from the pulmonary artery catheter to the pulse pressure analysis and Doppler techniques are discussed, with focus on this specific clinical setting. Undoubtedly monitoring is valuable tool, but without a protocol of how to manipulate the haemodynamics, no monitor will prove alone to be beneficial. Haemodynamic driven early goal directed therapy are largely awaited in this field of medicine.

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 (72h 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.

Dysglycemia, Glycemic Variability, and Outcome After Cardiac Arrest and Temperature Management at 33°C and 36°C.

Objectives: Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest. Design: Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as “Cerebral Performance Category.” Setting: Thirty-six sites in Europe and Australia. Patients: All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial. Interventions: Targeted temperature management at 33°C or 36°C. Measurements and Main Results: Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3–5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03–1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group. Conclusion: Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.

Perioperative kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass

INTRODUCTION Endothelial Specific Molecule-1 or endocan is a novel biomarker associated with the development of acute lung injury (ALI) in response to a systemic inflammatory state such as trauma. Acute Respiratory Distress syndrome (ARDS), a severe form of ALI is a devastating complication that can occur following cardiac surgery due to risk factors such as the use of cardiopulmonary bypass (CPB) during surgery. In this study we examine the kinetics of endocan in the perioperative period in cardiac surgical patients. METHODS After ethics approval, we obtained informed consent from 21 patients undergoing elective cardiac surgery (3 groups with seven patients in each group: coronary artery bypass grafting (CABG) with the use of CPB, off-pump CABG and complex cardiac surgery). Serial blood samples for endocan levels were taken in the perioperative period (T0: baseline prior to induction, T1: at the time of heparin administration, T2: at the time of protamine, T2, T3, T4 and T5 at 1, 2, 4 and 6h following protamine administration respectively). Endocan samples were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis incorporated the use of test for normality. RESULTS Our results reveal that an initial rise in the levels of serum endocan from baseline in all patients after induction of anaesthesia. Patients undergoing off-pump surgery have lower endocan concentrations in the perioperative period than those undergoing CPB. Endocan levels decrease following separation from CPB, which may be attributed to haemodilution following CPB. Following administration of protamine, endocan concentrations steadily increased in all patients, reaching a steady state between 2 and 6h. The baseline endocan concentrations were elevated in patients with hypertension and severe coronary artery disease. CONCLUSION Baseline endocan concentrations are higher in hypertensive patients with critical coronary artery stenosis. Endocan concentrations increased after induction of anaesthesia and decreased four hours after separation from CPB. Systemic inflammation may be responsible for the rise in endocan levels following CPB.