Jens Nee

Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients

IntroductionNeuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 μg/l. However, most of the corresponding studies were conducted before the introduction of mild therapeutic hypothermia (MTH). Therefore we conducted a study investigating the association between NSE and neurological outcome in patients treated with MTHMethodsIn this prospective observational cohort study the data of patients after cardiac arrest receiving MTH (n = 97) were consecutively collected and compared with a retrospective non-hypothermia (NH) group (n = 133). Serum NSE was measured 72 hours after admission to ICU. Neurological outcome was classified according to the Pittsburgh cerebral performance category (CPC 1 to 5) at ICU discharge.ResultsNSE serum levels were significantly lower under MTH compared to NH in univariate analysis. However, in a linear regression model NSE was affected significantly by time to return of spontaneous circulation (ROSC) and ventricular fibrillation rhythm but not by MTH. The model for neurological outcome identified NSE, NSE*MTH (interaction) as well as time to ROSC as significant predictors. Receiver Operating Characteristic (ROC) analysis revealed a higher cutoff value for unfavourable outcome (CPC 3 to 5) with a specificity of 100% in the hypothermia group (78.9 μg/l) compared to the NH group (26.9 μg/l).ConclusionsRecommended cutoff levels for NSE 72 hours after ROSC do not reliably predict poor neurological outcome in cardiac arrest patients treated with MTH. Prospective multicentre trials are required to re-evaluate NSE cutoff values for the prediction of neurological outcome in patients treated with MTH.

Mild hypothermia treatment in patients resuscitated from non-shockable cardiac arrest

Objective Therapeutic hypothermia has proved effective in improving outcome in patients after cardiac arrest due to ventricular fibrillation (VF). The benefit in patients with non-VF cardiac arrest is still not defined. Methods This prospective observational study was conducted in a university hospital setting with historical controls. Between 2002 and 2010 387 consecutive patients have been admitted to the intensive care unit (ICU) after cardiac arrest (control n=186; hypothermia n=201). Of those, in 175 patients the initial rhythm was identified as non-shockable (asystole, pulseless electrical activity) rhythm (control n=88; hypothermia n=87). Neurological outcome was assessed at ICU discharge according to the Pittsburgh cerebral performance category (CPC). A follow-up was completed for all patients after 90 days, a Kaplan–Meier analysis and Cox regression was performed. Results Hypothermia treatment was not associated with significantly improved neurological outcome in patients resuscitated from non-VF cardiac arrest (CPC 1–2: hypothermia 27.59% vs control 18.20%, p=0.175). 90-Day Kaplan–Meier analysis revealed no significant benefit for the hypothermia group (log rank test p=0.82), and Cox regression showed no statistically significant improvement. Conclusions In this cohort patients undergoing hypothermia treatment after non-shockable cardiac arrest do not benefit significantly concerning neurological outcome. Hypothermia treatment needs to be evaluated in a large multicentre trial of cardiac arrest patients found initially to be in non-shockable rhythms to clarify whether cooling may also be beneficial for other rhythms than VF.

Simplified lung ultrasound protocol shows excellent prediction of extravascular lung water in ventilated intensive care patients

IntroductionUltrasound of the lung and quantification of B lines was recently introduced as a novel tool to detect overhydration. In the present study, we aimed to evaluate a four-region protocol of lung ultrasound to determine the pulmonary fluid status in ventilated patients in the intensive care unit.MethodsFifty patients underwent both lung ultrasound and transpulmonary thermodilution measurement with the PiCCO system. An ultrasound score based on number of single and confluent B lines per intercostal space was used to quantify pulmonary overhydration. To check for reproducibility, two different intensivists who were blinded as to the ultrasound pictures reassessed and classified them using the same scoring system. The results were compared with those obtained using other methods of evaluating hydration status, including extravascular lung water index (EVLWI) and intrathoracic blood volume index calculated with data from transpulmonary thermodilution measurements. Moreover, chest radiographs were assessed regarding signs of pulmonary overhydration and categorized based on a numeric rating scale.ResultsLung water assessment by ultrasound using a simplified protocol showed excellent correlation with EVLWI over a broad range of lung hydration grades and ventilator settings. Correlation of chest radiography and EVLWI was less accurate. No correlation whatsoever was found with central venous pressure measurement.ConclusionLung ultrasound is a useful, non-invasive tool in predicting hydration status in mechanically ventilated patients. The four-region protocol that we used is time-saving, correlates well with transpulmonary thermodilution measurements and performs markedly better than chest radiography.

Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

BackgroundNeuron specific enolase (NSE) has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia.MethodsIn a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines.ResultsThe cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5) 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC) of 0.82 (sensitivity 47%, specificity 100%). The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5) was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100%) and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100%) at 48 hours compared to admission.ConclusionIn cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

Regional cerebral oxygen saturation after cardiac arrest in 60 patients—A prospective outcome study

INTRODUCTION Non-invasive near-infrared spectroscopy (NIRS) offers the possibility to determine regional cerebral oxygen saturation (rSO2) in patients with cardiac arrest. Limited data from recent studies indicate a potential for early prediction of neurological outcome. METHODS Sixty cardiac arrest patients were prospectively enrolled, 22 in-hospital cardiac arrest (IHCA) and 38 out-of-hospital cardiac arrest (OHCA) patients respectively. NIRS of frontal brain was started after return of spontaneous circulation (ROSC) during admission to ICU and was continued until normothermia. Outcome was determined at ICU discharge by the Pittsburgh Cerebral Performance Category (CPC) and 6 months after cardiac arrest. RESULTS A good outcome (CPC 1-2) was achieved in 23 (38%) patients, while 37 (62%) had a poor outcome (CPC 3-5). Patients with good outcome had significantly higher rSO2 levels (CPC 1-2: rSO2 68%; CPC 3-5: rSO2 58%; p<0.01). For good and poor outcome median rSO2 within the first 24h period was 66% and 59% respectively and for the following 16h period 68% and 59% (p<0.01). Outcome prediction by area of rSO2 below a critical threshold of rsO2=50% within the first 40h yielded 70% specificity and 86% sensitivity for poor outcome. CONCLUSION On average, rSO2 within the first 40h after ROSC is significantly lower in patients with poor outcome, but rSO2 ranges largely overlap between outcome groups. Our data indicate limited potential for prediction of poor outcome by frontal brain rSO2 measurements.

Severe QTc prolongation under mild hypothermia treatment and incidence of arrhythmias after cardiac arrest--a prospective study in 34 survivors with continuous Holter ECG.

BACKGROUND Mild hypothermia treatment (32-34°C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h. PATIENTS AND METHODS A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients. RESULTS During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00 ms; IQR 424.25-476.75; n=17) but during hypothermia treatment the QTc interval was significantly prolonged at 33°C after 24h of cooling (564.47 ms; IQR 512.41-590.00; p=0.0001; n=34) and decreased after end of hypothermia to baseline levels (476.74 ms; 448.71-494.97; p=0.15). CONCLUSION The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670 ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.

2-year survival of patients undergoing mild hypothermia treatment after ventricular fibrillation cardiac arrest is significantly improved compared to historical controls

BackgroundTherapeutic hypothermia has been proven to be effective in improving neurological outcome in patients after cardiac arrest due to ventricular fibrillation (VF). Data concerning the effect of hypothermia treatment on long-term survival however is limited.Materials and methodsClinical and outcome data of 107 consecutive patients undergoing therapeutic hypothermia after cardiac arrest due to VF were compared with 98 historical controls. Neurological outcome was assessed at ICU discharge according to the Pittsburgh cerebral performance category (CPC). A Kaplan-Meier analysis of follow-up data concerning mortality after 24 months as well as a Cox-regression to adjust for confounders were calculated.ResultsNeurological outcome significantly improved after mild hypothermia treatment (hypothermia group CPC 1-2 59.8%, control group CPC 1-2 24.5%; p < 0.01). In Kaplan-Meier survival analysis hypothermia treatment was also associated with significantly improved 2-year probability for survival (hypothermia 55% vs. control 34%; p = 0.029). Cox-regression analysis revealed hypothermia treatment (p = 0.031) and age (p = 0.013) as independent predictors of 24-month survival.ConclusionsOur study demonstrates that the early survival benefit seen with therapeutic hypothermia persists after two years. This strongly supports adherence to current recommendations regarding postresuscitation care for all patients after cardiac arrest due to VF and maybe other rhythms as well.

Tympanic temperature during therapeutic hypothermia

Objective Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia. Methods Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements. Results Compared with oesophageal temperature, bladder temperature had a bias of 0.019°C (limits of agreement ±0.61°C (2SD)), and tympanic measurement had a bias of 0.021°C (±0.80°C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r=0.95, p<0.0001) and also for tympanic versus bladder temperature (r=0.96, p<0.0001). Conclusions That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring.

A survey on general and temperature management of post cardiac arrest patients in large teaching and university hospitals in 14 European countries—The SPAME trial results

INTRODUCTION International guidelines recommend a bundle of care, including targeted temperature management (TTM), in post cardiac arrest survivors. Aside from a few small surveys in different European countries, adherence to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) recommendations are unknown. METHODS This international European telephone survey was conducted to provide an overview of current clinical practice of post cardiac arrest management with a main focus on TTM. We targeted large teaching and university hospitals within Europe as leading facilities and key opinion leaders in the field of post cardiac arrest care. Selected national principal investigators conducted the survey, which was based on a predefined questionnaire, between December 2014 and March 2015, before the publication of the ERC Guidelines 2015. RESULTS The return rate was 94% from 268 participating intensive care units (ICU). The majority had a predefined standard operating procedure (SOP) protocol for post cardiac arrest patients. Altogether, 68% of the ICUs provided TTM at a target temperature of 32-34°C for 24h, and 33% had changed the target temperature to 36°C. The minority provided a written SOP for neurological prognostication, which was generally initiated 72h after return of spontaneous circulation (ROSC). Electroencephalography and somatosensory evoked potentials were used by most ICUs for early prognostication. Treating more than fifty patients a year was significantly associated with providing written SOPs for TTM and prognostication (p<0.01), as well as the use of a computer feedback device (p=0.03) for TTM. CONCLUSION This international European telephone survey revealed a high rate of implementation of TTM in post cardiac arrest patients in university and teaching hospitals. Most participants also provided a SOP, but only a minority had a SOP for neurological prognostication.

Improvement of cerebral oxygen saturation after successful electrical cardioversion of atrial fibrillation

AIMS Cerebral and microvascular perfusion is reduced in atrial fibrillation (AF). Maintenance of brain perfusion is important in acute disease and long-term course. Assessment of brain perfusion and oxygenation is difficult in clinical practice. Our study aimed to determine changes in cerebral tissue oxygen saturation (SctO2) with bedside near-infrared spectroscopy (NIRS). METHODS AND RESULTS Twenty patients (mean age 67.7 ± 10.2 years, 50% men) in whom electrical cardioversion (CV) was successful were prospectively studied. Ten patients (mean age 64.2 ± 7.7 years, 80% men) in whom CV was not successful served as control group. Bilateral SctO2, mean arterial pressure (MAP), arterial oxygen saturation (SaO2), and heart rate were recorded and changes of all parameters before and after CV were compared between the groups. Our results show an increase in SctO2 after successful CV that was significantly higher compared with patients who remained in AF (right SctO2 3.25 ± 2.5 vs. -0.13 ± 0.52%, P = 0.001; left SctO2 4.27 ± 3.56 vs. -0.38 ± 2.4%, P < 0.001). Neither arterial blood pressure nor SaO2 changes differed significantly between the two groups. No correlation could be detected between the significant increase of SctO2 after successful CV and arterial blood pressure, SaO2, or heart rate. CONCLUSION Cerebral tissue oxygen saturation increases significantly after restoration of sinus rhythm. Near-infrared spectroscopy monitoring can identify changes of SctO2 after successful CV of AF independent from standard monitoring parameters (MAP, SaO2). Near-infrared spectroscopy can be used to detect cerebral oxygen saturation deficits in AF patients or patients at high risk for AF. Clinical applications may include monitoring during ablation procedures and in critical care.