Dietrich Hasper

Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest

Background: Bilateral absent N20 responses of median nerve somatosensory evoked potentials (SEPs) reliably predict poor prognosis after cardiac arrest. However, the studies supporting this fact were carried out before hypothermia was established as standard treatment. Recent evidence suggests that hypothermia treatment affects the predictive value of clinical findings in cardiac arrest patients, raising the question whether the predictive value of N20 responses has changed as well. Methods: We retrospectively studied 185 consecutive patients treated with hypothermia after cardiac arrest. SEP recordings were available for 112 patients. SEPs were classified as bilateral absent N20, pathologic N20, or normal. Baseline and follow-up information were obtained from our database. Results: We identified 36 patients with bilateral absent N20, 35 (97%) of whom had poor outcome. One patient had prolonged high amplitude peripheral SEP, but bilaterally absent N20 3 days after cardiac arrest and regained consciousness with normal cognitive functions and reproducible N20 responses. One further patient had minimally detectable N20 at day 3 and recovered consciousness and normal N20 responses on follow-up. Conclusions: Our data indicate that recovery of consciousness and cognitive functions is possible in spite of absent or minimally present N20 responses more than 24 hours after cardiac arrest in a very small proportion of patients. N20 responses may recover beyond this time window. The predictive value of bilateral absent N20 responses needs to be reevaluated in larger prospective studies. Until these studies are available, decisions to stop therapy in cardiac arrest survivors should not be based on N20 responses alone.

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.

Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms.

BACKGROUND Tryptophan (Trp) is catabolized by indoleamine 2,3-dioxygenase (IDO). Changes in Trp metabolism and IDO activity in chronic kidney disease (CKD) have not been widely studied, and the impact of haemodialysis is uncertain. Here we investigate Trp catabolism, IDO activity and the role of inflammation in moderate to very severe CKD and haemodialysis. METHODS Eighty individuals were included in a prospective blinded endpoint analysis. Using tandem mass spectrometry, serum levels of Trp, kynurenine (Kyn), kynurenic-acid (Kyna), quinolinic-acid (Quin), 5-hydroxytryptophan (OH-Trp), serotonin (5-HT), estimated IDO activity and inflammatory markers were assessed in 40 CKD patients (age 57 +/- 14 years, 21 male, creatinine 4.5 +/- 2.7, n = 17 receiving haemodialysis), and in 40 healthy controls (age 34 +/- 9 years, 26 male). RESULTS Trp levels were unchanged in CKD (P = 0.78 versus controls). Serum levels of Kyn, Kyna and Quin increased with CKD severity (stages 4, 5 versus controls all P < or = 0.01). IDO activity was significantly induced in CKD and correlated with disease severity (stages 3-5 versus controls, all P < or = 0.01) and inflammatory markers [high-sensitivity C-reactive protein (hsCRP), soluble TNF-receptor-1 (sTNFR-I); both P < or = 0.03]. IDO products (Kyn, Kyna, Quin) correlated also with hsCRP and sTNFR-I (all P < or = 0.04). Haemodialysis did not influence IDO activity (P = 0.26) and incompletely removed Kyn, Kyna, Quin, OH-Trp and 5-HT by 22, 26, 50, 44 and 34%, respectively. In multiple regression, IDO activity correlated with hsCRP and sTNFR-I (both P < or = 0.03) independent of serum creatinine, age and body weight. CONCLUSIONS IDO activity and serum levels of tryptophan catabolites of the kynurenine pathway increase with CKD severity. In CKD, induction of IDO may primarily be a consequence of chronic inflammation.

Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls

IntroductionPersistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest.MethodsA prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used.ResultsIn survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013).ConclusionTherapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest. Moreover, profound improvements in both neurological outcome and 1-year survival were observed.

INFERIOR VENA CAVA DIAMETER CORRELATES WITH INVASIVE HEMODYNAMIC MEASURES IN MECHANICALLY VENTILATED INTENSIVE CARE UNIT PATIENTS WITH SEPSIS

Early optimization of fluid status is of central importance in the treatment of critically ill patients. This study aims to investigate whether inferior vena cava (IVC) diameters correlate with invasively assessed hemodynamic parameters and whether this approach may thus contribute to an early, non-invasive evaluation of fluid status. Thirty mechanically ventilated patients with severe sepsis or septic shock (age 60 +/- 15 years; APACHE-II score 31 +/- 8; 18 male) were included. IVC diameters were measured throughout the respiratory cycle using transabdominal ultrasonography. Consecutively, volume-based hemodynamic parameters were determined using the single-pass thermal transpulmonary dilution technique. This was a prospective study in a tertiary care academic center with a 24-bed medical intensive care unit (ICU) and a 14-bed anesthesiological ICU. We found a statistically significant correlation of both inspiratory and expiratory IVC diameter with central venous pressure (p = 0.004 and p = 0.001, respectively), extravascular lung water index (p = 0.001, p < 0.001, respectively), intrathoracic blood volume index (p = 0.026, p = 0.05, respectively), the intrathoracic thermal volume (both p < 0.001), and the PaO(2)/FiO(2) oxygenation index (p = 0.007 and p = 0.008, respectively). In this study, IVC diameters were found to correlate with central venous pressure, extravascular lung water index, intrathoracic blood volume index, the intrathoracic thermal volume, and the PaO(2)/FiO(2) oxygenation index. Therefore, sonographic determination of IVC diameter seems useful in the early assessment of fluid status in mechanically ventilated septic patients. At this point in time, however, IVC sonography should be used only in addition to other measures for the assessment of volume status in mechanically ventilated septic patients.

The Glasgow coma score is a predictor of good outcome in cardiac arrest patients treated with therapeutic hypothermia

BACKGROUND With the recent introduction of therapeutic hypothermia the application of sedation becomes necessary in cardiac arrest patients. We therefore analysed the usefulness of the Glasgow coma score (GCS) for outcome prediction in survivors of cardiac arrest treated with therapeutic hypothermia. PATIENTS AND METHODS In a prospective observational study we identified 72 comatose patients admitted to our intensive care unit after cardiac arrest. All patients were treated with therapeutic hypothermia. After sedation stop the Glasgow coma scale (GCS) was recorded until day 4. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. RESULTS Forty-four of 72 patients (61%) were discharged with a favourable neurological outcome (CPC 1+2). GCS was significantly higher in patients with good outcome compared to patients with unfavourable outcome at every point in time after sedation stop (p<0.001). The value for prediction of good outcome with the highest accuracy was a GCS>4 at the first day after sedation stop (sensitivity 61%, PPV 90% and AUC 0.808) and GCS>6 in the following days (sensitivity 84%, PPV 92.5% and AUC 0.921 at day 4). In particular a score of >3 on the motor component of the GCS predicted good outcome with a specificity of 100% (sensitivity 43%) at the first day. CONCLUSIONS Our results indicate that monitoring of the GCS is a simple and reliable method for clinical outcome assessment in patients treated with therapeutic hypothermia. Thus, GCS monitoring remains a powerful tool to predict outcome of patients treated with therapeutic hypothermia.

Mild therapeutic hypothermia after cardiac arrest and the risk of bleeding in patients with acute myocardial infarction

BACKGROUND The aim of the study was to report the impact of our hypothermia protocol on survival and neurological outcome. Furthermore, we were interested in the risk of bleeding complications in patients with acute myocardial infarction (AMI) being treated with percutaneous coronary revascularisation (PCI) and therapeutic hypothermia. METHODS AND RESULTS In a prospective observational study we identified 31 comatose patients (25 male, age 65+/-13 years) admitted to our intensive care unit with out-of-hospital cardiac arrest due to AMI who were treated with hypothermia. They were compared to 31 historical age- and gender-matched controls (25 male, age 65+/-12 years) admitted after out-of-hospital cardiac arrest due to AMI in the era prior to hypothermia treatment. Peak creatinine kinase-MB was 118 U/L (94-248) in the hypothermia group and 131 U/L (98-257) in controls (p=0.51). In the hypothermia group, 19 patients were discharged with a favourable neurological outcome, whereas in controls, such outcome was observed in only six patients (p=0.002). In both groups, haemoglobin values and platelet counts declined during the first 48 h (all p<0.001). No differences regarding bleeding complications (p=1.0), transfusion requirements (p=1.0), and the number of transfusions (p=0.9) were observed between the groups. CONCLUSIONS A major improvement in neurological outcome was observed in patients treated with hypothermia. Our results indicate that the combination of reperfusion strategies and the application of hypothermia do not carry an excessive risk of bleeding complications. Patients with AMI and out-of-hospital cardiac arrest should receive the optimal therapy for both conditions, that is, either thrombolysis or PCI and therapeutic hypothermia.

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.

Changes in serum creatinine in the first 24 hours after cardiac arrest indicate prognosis: an observational cohort study

IntroductionAs patients after cardiac arrest suffer from the consequences of global ischemia reperfusion, we aimed to establish the incidence of acute kidney injury (AKI) in these patients, and to investigate its possible association to severe hypoxic brain damage.MethodsOne hundred and seventy-one patients (135 male, mean age 61.6 +/- 15.0 years) after cardiac arrest were included in an observational cohort study. Serum creatinine was determined at admission and 24, 48 and 72 hours thereafter. Serum levels of neuron-specific enolase (NSE) were measured 72 hours after admission as a marker of hypoxic brain damage. Clinical outcome was assessed at intensive care unit (ICU) discharge using the Pittsburgh cerebral performance category (CPC).ResultsAKI as defined by AKI Network criteria occurred in 49% of the study patients. Patients with an unfavourable prognosis (CPC 3-5) were affected significantly more frequently (P = 0.013). Whilst serum creatinine levels decreased in patients with good neurological outcome (CPC 1 or 2) over the ensuing 48 hours, it increased in patients with unfavourable outcome (CPC 3-5). ROC analysis identified DeltaCrea24 <-0.19 mg/dl as the value for prediction with the highest accuracy. The odds ratio for an unfavourable outcome was 3.81 (95% CI 1.98-7.33, P = 0.0001) in cases of unchanged or increased creatinine levels after 24 hours compared to those whose creatinine levels decreased during the first 24 hours. NSE levels were found to correlate with the change in serum creatinine in the first 24 hours both in simple and multivariate regression (both r = 0.24, P = 0.002).ConclusionsIn this large cohort of patient after cardiac arrest, we found that AKI occurs in nearly 50% of patients when the new criteria are applied. Patients with unfavourable neurological outcome are affected more frequently. A significant association between the development of AKI and NSE levels indicating hypoxic brain damage was observed. Our data show that changes in serum creatinine may contribute to the prediction of outcome in patients with cardiac arrest. Whereas a decline in serum creatinine (> 0.2 mg/dL) in the first 24 hours after cardiac arrest indicates good prognosis, the risk of unfavourable outcome is markedly elevated in patients with constant or increasing serum creatinine.

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.