S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment

Objective

To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest.

Design

Prospective observational study.

Setting

One intensive care unit at Uppsala University Hospital.

Patients

Thirty-one unconscious patients resuscitated after cardiac arrest.

Interventions

None.

Measurements and main results

Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34 °C for 26 h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108 h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24 h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96 h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome.

Conclusions

The blood concentration of S-100B at 24 h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.     

Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia

Aim

To assess the prognostic value of repetitive serum samples of neuron specific enolase (NSE) and S-100B in cardiac arrest patients treated with hypothermia.

Methods

In a three-centre study, comatose patients after cardiac arrest were treated with hypothermia at 33 °C for 24 h, regardless of cause or the initial rhythm. Serum samples were collected at 2, 24, 48 and 72 h after the arrest and analysed for NSE and S-100B in a non-blinded way. The cerebral performance categories scale (CPC) was used as the outcome measure; a best CPC of 1–2 during 6 months was regarded as a good outcome, a best CPC of 3–5 a poor outcome.

Results

One centre was omitted in the NSE analysis due to missing 24 and 48 h samples. Two partially overlapping groups were studied, the NSE group (n = 102) and the S-100B group (n = 107). NSE at 48 h >28 μg/l (specificity 100%, sensitivity 67%) and S-100B >0.51 μg/l at 24 h (specificity 96%, sensitivity 62%) correlated with a poor outcome, and so did a rise in NSE of >2 μg/l between 24 and 48 h (odds ratio 9.8, CI 3.5–27.7). A majority of missing samples (n = 123) were from the 2 h sampling time (n = 56) due to referral from other hospitals or inter-hospital transfer.

Conclusion

NSE was a better marker than S-100B for predicting outcome after cardiac arrest and induced hypothermia. NSE above 28 μg/l at 48 h and a rise in NSE of more than 2 μg/l between 24 and 48 h were markers for a poor outcome.     

Brain biomarkers and management of uncertainty in predicting outcome of cardiopulmonary resuscitation: A nomogram paints a thousand words

Aim

Use of brain biomarkers for predicting death after cardiopulmonary resuscitation (CPR) is limited by a research focus on the discriminative ability of each biomarker and ethical/cultural controversy concerning the likelihood of misclassification of potential survivors. We illustrate an approach to address these limitations by creating a dynamic nomogram with four levels of sensitivity (0.8, 0.9, 0.95 and 1.0) selected to represent different degrees of certainty in correct identification of survivors.

Methods

A prolective observational study conducted in a single 850-bed hospital. Admission serum S100beta (S100B) and neuron-specific enolase (NSE) were determined for all adult survivors of non-traumatic out-of-hospital arrest and CPR.

Results

158 patients were included, 126 (80%) died in hospital, 32 (20%) survived. Non-survivors had higher admission biomarker levels than survivors (p ≤ 0.001 for both S100B and NSE). Presenting rhythm (VT/VF vs. other) and logarithmic-transformed S100B and NSE levels were statistically significant in the multivariable model predicting survival. The area under the model ROC curve was 0.868 (95%CI 0.80, 0.936). Plots for predicting survival for each combination of biomarker levels were generated for each sensitivity with and without VT/VF, allowing clinicians to select their option in terms of survival probability. In this modest-sized illustrative study the model misclassified 1/19 patients with Cerebral Performance Category 1–2 for sensitivity >0.80.

Conclusions

We demonstrate how brain biomarkers can serve as decision support tools after CPR despite ethical/cultural differences in defining futility. Data from larger and diverse samples are required for stable estimates prior to clinical implementation of such a tool.     

NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest

Introduction

Prognostication of cardiac arrest survivors is challenging since therapeutic hypothermia (TH) has been introduced. We evaluated serum biomarkers and motor response.

Methods

This was a retrospective data analysis including patients in the years 2007–2012. Blood was drawn and a neurological examination was performed on admission and every morning. Outcomes were evaluated 6 months after discharge and dichotomized into good (cerebral performance category (CPC) = 1 or 2) and poor (CPC = 3, 4 or 5).

Results

123 patients (79.7% male, 63 ± 14 years) received TH; 50% had a good outcome. On admission, S-100B (P = 0.004) was significantly associated with the outcome, as well as neuron-specific enolase (NSE; P = 0.020) and S-100B (P = 0.004) on day 1 after admission. NSE on day 2, NSE progression from day 1 to 2 and motor response on day 3 also predicted the outcome (all P < 0.001).NSE > 33 μg l⁻¹ only predicted a poor outcome with a specificity of 76%. An absent motor response on day 3 was the most sensitive marker (94%). NSE > 41.1 μg l⁻¹ combined with S-100B > 0.461 μg l⁻¹ on day 1 was the most specific marker (96%).

Conclusion

Although NSE and S-100B levels are associated with the outcome, the use of previously described cut-off values was insufficiently predictive of neurologic outcome. Caution should be exercised in the use of these tests to provide neuroprognostication.     

Early kynurenine pathway activation following cardiac arrest in rats,pigs, and humans

Aim of the study

Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. In the present study, TRP and KP metabolites concentrations were measured in plasma from rats, pigs and humans after cardiac arrest (CA) in order to assess KP activation and its potential role in post-resuscitation outcome.

Methods

Plasma was obtained from: (A) 24 rats, subjected to 6 min CA and 6 min of cardiopulmonary resuscitation (CPR); (B) 10 pigs, subjected to 10 min CA and 5 min CPR; and (C) 3 healthy human volunteers and 5 patients resuscitated from CA. KP metabolites were quantified by liquid chromatography multiple reaction monitoring mass spectrometry. Assessments were available at baseline, and 1–4 h, and 3–5 days post-CA.

Results

KP was activated after CA in rats, pigs, and humans. Decreases in TRP occurred during the post-resuscitation period and were accompanied by significant increases in its major metabolites, 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid in each species, that persisted up to 3–5 days post-CA (p < 0.01). In rats, changes in KP metabolites reflected changes in post-resuscitation myocardial function. In pigs, changes in TRP and increases in 3-HAA were significanlty related to the severity of cerebral histopathogical injuries. In humans, KP activation was observed, together with systemic inflammation. Post-CA increases in 3-HAA were greater in patients that did not survive.

Conclusion

In this fully translational investigation, the KP was activated early following resuscitation from CA in rats, pigs, and humans, and might have contributed to post-resuscitation outcome.     

Serum glial fibrillary acidic protein as a predictive biomarker of neurological outcome after cardiac arrest

Aim of the study

Serum glial fibrillary acidic protein (GFAP) has recently been identified as a specific predictor of brain damage and neurological outcome in patients with head trauma. In this study, serum GFAP was assessed as a predictor of neurological outcome in post-cardiac-arrest (PCA) patients.

Methods

This study was a retrospective, single-medical-center analysis, conducted in the intensive care unit of a university hospital. Forty-four sequential PCA patients with cardiogenic or non-cardiogenic arrest were included. The patients were treated with or without therapeutic hypothermia (TH). Serum samples were collected from the patients at 12, 24, and 48 h after the return of spontaneous circulation (ROSC). Serum GFAP concentrations were measured by enzyme-linked immunosorbent assay and compared in patients with good and poor neurological outcomes, evaluated over a period of 6 months using Glasgow Outcome Scale.

Results

Serum GFAP was significantly higher in patients with a poor outcome at 12 and 24 h without TH and at 48 h with TH (P < 0.05). GFAP (>0.1 ng dL⁻¹) was a specific predictor of poor neurological outcome at 6 months with or without TH treatment.

Conclusions

Although this study is preliminary, serum GFAP after ROSC reflected a poor neurological outcome in PCA patients.     

Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: Results using a single (24 h) time-point

Background and objectives

In recent years, biochemical markers have been employed to predict the outcome of patients with traumatic brain injury (TBI). In mild TBI, S100B has shown the most promise as a marker of outcome. The objective of this study in patients with severe TBI was to: show the range of serum S100B levels during the acute phase after trauma: determine if S100B has potential to discriminate favourable from unfavourable outcome in patients with similar brain injury severity scores and to establish an S100B ‘cut-off’ predictive for death.

Methods

All patients with severe TBI, admitted to this neurointensive care unit within 24 h of injury were eligible for inclusion in the study. One serum blood sample was obtained from each patient at the 24 h post-injury time-point. S100B levels were measured using enzyme-linked immunosorbent assay. Injuries were coded using an internationally recognised injury severity scoring system (ISS). Three-month follow-up was undertaken with outcome assessed using the Glasgow outcome score (GOS).

Results

One hundred patients were recruited. Serum S100B levels ranged from 0.08 to 12.62 μg L⁻¹ S100B levels were significantly higher in patients with a GOS of 1 (death) 2 and 3 (unfavourable outcome) compared with those with GOS 4 and 5 (good recovery). In this study a cut-off point of 0.53 μg L⁻¹ has sensitivity of >80% and specificity of 60% to predict unfavourable outcome and 49% to predict death.

Conclusion

In 100 patients studied with similar brain injury severity scores, serum S100B measured at the 24-h time-point after injury is significantly associated with outcome but a cut-off 0.53 μg L⁻¹ does not have good prognostic performance.     

Association of serum lactate and survival outcomes in patients undergoing therapeutic hypothermia after cardiac arrest

Introduction

Recent studies have suggested that serum lactate may serve as a marker to predict mortality after resuscitation from cardiac arrest (CA). The relationship between serum lactate and CA outcomes requires further characterization, especially among patients treated with therapeutic hypothermia (TH) and aggressive post-arrest care.

Methods

A retrospective analysis of patients resuscitated from non-traumatic CA at three urban U.S. hospitals was performed using an established internet-based post-arrest registry. Adult (≥18 years) patients resuscitated from CA and receiving TH treatment were included. Logistic regression analysis was used to adjust for potential confounders to survival outcomes. Survival to discharge served as the primary endpoint.

Results

A total of 199 post-CA patients treated with TH between 5/2005 and 11/2011 were included in this analysis. The mean age was 56.9 ± 16.5 years, 85/199 (42.7%) patients were female, and survival to discharge was attained in 84/199 (42.2%). While lower initial post-CA serum lactate levels were not associated with increased survival to discharge, subsequent lactate measurements were significantly associated with outcomes (24-h serum lactate levels in survivors vs. non-survivors, 2.7 ± 0.5 vs. 4.2 ± 0.4 mmol/L, p < 0.01). Multivariable logistic regression confirmed this relationship with survival to discharge (p < 0.01).

Conclusion

Lower serum lactate levels at 12 h and 24 h, but not initially following cardiac arrest, are associated with survival to hospital discharge after resuscitation from CA and TH treatment. Prospective investigation of serum lactate as a potential prognostic tool in CA is needed.     

Combining brain computed tomography and serum neuron specific enolase improves the prognostic performance compared to either alone in comatose cardiac arrest survivors treated with therapeutic hypothermia

Aim of the study

We determined whether combining the grey-to-white matter ratio (GWR) on brain computed tomography (CT) and serum neuron specific enolase (NSE) improves the prognostic performance when compared to either alone in cardiac arrest patients treated with therapeutic hypothermia (TH).

Methods

We performed a retrospective study of a cohort of cardiac arrest patients treated with TH. The Hounsfield unit was measured in the caudate nucleus (CN), putamen (P), posterior limb of internal capsule (PIC) and corpus callosum (CC); GWR was calculated as CN/PIC and P/CC. The NSE value was obtained at 0, 24, and 48 h after restoration of spontaneous circulation (ROSC). We analysed the prognostic performance of GWR and NSE, singly and in combination, in predicting poor neurologic outcome (cerebral performance category 3–5).

Results

Of the 224 included patients, 82 showed good neurologic outcome at hospital discharge, while 142 showed poor neurologic outcome. The P/CC (area under receiver operating characteristics (AUROC) 0.864, sensitivity/specificity 52.9%/100%) showed better prognostic performance than did the CN/PIC (AUROC 0.721, sensitivity/specificity 19.8%/100%). The NSE value at 48 h after ROSC (AUROC 0.895, sensitivity/specificity 60.2%/100%) showed the highest prognostic value among the three NSE time points. Analysis of 119 patients undergoing both brain CT and NSE at 48 h indicated that combining P/CC and NSE improved the sensitivity (78.6%) compared to either alone (48.6%, 62.9%).

Conclusion

Combining brain CT and serum NSE improves the prognostic performance when compared to either alone in predicting poor neurologic outcome in cardiac arrest patients treated with TH.     

The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

Introduction

Therapeutic Hypothermia (TH) has become a standard of care in improving neurological outcomes in cardiac arrest (CA) survivors. Previous studies have defined severe acidemia as plasma pH < 7.20. We investigated the influence of severe acidemia at the time of initiation of TH on neurological outcome in CA survivors.

Methods

A retrospective analysis was performed on 196 consecutive CA survivors (out-of-hospital CA and in-hospital CA) who underwent TH with endovascular cooling between January 2007 and October 2012. Arterial blood gas drawn prior to initiation of TH was utilized to measure pH in all patients. Shockable and non-shockable CA patients were divided into two sub-groups based on pH (pH < 7.2 and pH ≥ 7.2). The primary end-point was measured using the Pittsburgh Cerebral Performance Category (CPC) scale prior to discharge from the hospital: good (CPC 1 and 2) and poor (CPC 3 to 5) neurologic outcome.

Results

Sixty-two percent of shockable CA patients with pH ≥ 7.20 had good neurological outcome as compared to 34% patients with pH < 7.20. Shockable CA patients with pH ≥ 7.20 were 3.3 times more likely to have better neurological outcome when compared to those with pH <7.20 [p = 0.013, OR 3.3, 95% CI (1.28–8.45)]. In comparison, non-shockable CA patients with p ≥ 7.20 did not have a significantly different neurological outcome as compared to those with pH < 7.20 [p = 0.97, OR 1.02, 95% CI (0.31–3.3)].

Conclusion

Presence of severe acidemia at initiation of TH in shockable CA survivors is significantly associated with poor neurological outcomes. This effect was not observed in the non-shockable CA survivors.     

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 24 h 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 12.5 h, 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 12.5 h 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 12.5 h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest.     

Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: A prospective observational cohort study

Aims of the study

This study aimed to evaluate if the microcirculation is impaired during and after therapeutic hypothermia (TH) in children with return of spontaneous circulation after cardiac arrest (CA) and to assess if microcirculatory impairment predicts mortality. This has been reported for post-CA adults, but results might be different for children because etiology, pathophysiology, and mortality rate differ.

Methods

This prospective observational cohort study included consecutive, non-neonatal post-CA children receiving TH upon intensive care admission between June 2008 and June 2012. Also included were gender-matched and age-matched normothermic, control children without cardiorespiratory disease. The buccal microcirculation was non-invasively assessed with Sidestream Dark Field Imaging at the start of TH, halfway during TH, at the start of re-warming, and at normothermia. Macrocirculatory, respiratory, and biochemical parameters were also collected.

Results

Twenty post-CA children were included of whom 9 died. During hypothermia, the microcirculation was impaired in the post-CA patients and did not change over time. At normothermia, the core body temperature and the microcirculation had increased and no longer differed from the controls. Microcirculatory deterioration was associated with mortality in the post-CA patients. In particular, the microcirculation was more severely impaired at TH start in the non-survivors than in the survivors – positive predictive value: 73–83, negative predictive value: 75–100, sensitivity: 63–100%, and specificity: 70–90%.

Conclusions

The microcirculation is impaired in post-CA children during TH and more severe impairment at TH start was associated with mortality. After the stop of TH, the microcirculation improves rapidly irrespective of outcome.     

Heparin-binding protein: An early indicator of critical illness and predictor of outcome in cardiac arrest

Aim

To investigate plasma levels of the neutrophil-borne heparin-binding protein (HBP) in patients with induced hypothermia after cardiac arrest (CA), and to study any association to severity of organ failure, incidence of infection and neurological outcome.

Methods

This study included 84 patients with CA of mixed origin who were treated with hypothermia. Plasma samples from 7 time points during the first 72 h after return of spontaneous circulation (ROSC) were collected and analyzed for HBP with an ELISA. Outcomes were dichotomized: a cerebral performance category scale (CPC) of 1–2 at 6 months follow-up was considered a good outcome, a CPC of 3–5, a poor outcome. Patient data, including APACHE II and SOFA-scores were retrieved from the computerized system for quality assurance for intensive care.

Results

At 6 h and 12 h after CA, plasma levels of HBP were significantly higher among patients with a poor outcome. A receiver operated characteristics (ROC)-analysis yielded respective areas under curve (AUC) values of 0.68 and 0.70. This was similar to APACHE II and SOFA-score AUC values. There was a significant correlation between early elevated HBP-values and time to ROSC. HBP-levels were not higher in patients with infections at any time.

Conclusions

Elevated HBP is an early indicator of organ failure and poor neurological outcome after CA, independent of microbial infection, and should be further evaluated in prospective trials. The temporal profile of HBP is suggestive of a role in the pathogenesis of critical illness after CA.     

C-reactive protein levels after cardiac arrest in patients treated with therapeutic hypothermia

Aim

Prognostication of outcome after cardiac arrest (CA) is challenging. We assessed the prognostic value of daily blood levels of C-reactive protein (CRP), a cheap and widely available inflammatory biomarker, after CA.

Methods

We reviewed the data of all patients admitted to our intensive care unit (ICU) after CA between January 2009 and December 2011 and who survived for at least 24 h. We collected demographic data, CA characteristics (initial rhythm; location of arrest; time to return of spontaneous circulation [ROSC]), occurrence of infection, ICU survival and neurological outcome at three months (good = cerebral performance category [CPC] 1–2; poor = CPC 3–5). CRP levels were measured daily from admission to day 3.

Results

A total of 130 patients were admitted after successful resuscitation from CA and survived more than 24 h; 76 patients (58%) developed an infection and overall mortality was 56%. CRP levels increased from admission to day 3. CRP levels were higher in in-hospital than in out-of-hospital CA, especially on admission and day 1 (44.1 vs. 2.1 mg L⁻¹ and 74.5 vs. 29.5 mg L⁻¹, respectively; p < 0.001), and in patients with non-shockable than in those with shockable rhythms. In a logistic regression model, high CRP levels on admission were independently associated with poor neurological outcome at 3 months.

Conclusion

CRP levels increase in the days following successful resuscitation of CA. Higher CRP levels in patients with in-hospital CA, non-shockable rhythms and infection, suggest a greater inflammatory response in these patients. High CRP levels on admission may identify patients at high-risk of poor outcome and could be a target for future therapies.     

New treatment bundles improve survival in out-of-hospital cardiac arrest patients: A historical comparison

Introduction

Before the introduction of the new international cardiac arrest treatment guidelines in 2005, patients with out-of-hospital cardiac arrest (OHCA) of cardiac origin in Northern Italy had very poor prognosis. Since 2006, a new bundle of care comprising use of automated external defibrillators (AEDs) and therapeutic hypothermia (TH) was started, while extracorporeal CPR program (ECPR) for selected refractory CA and dispatcher-assisted cardio-pulmonary resuscitation (CPR) was started in January 2010.

Objectives

We hypothesized that a program of bundled care might improve outcome of OHCA patients.

Methods

We analyzed data collected in the OHCA registry of the MB area between September 2007 and August 2011 and compared this with data from 2000 to 2003.

Results

Between 2007 and 2011, 1128 OHCAs occurred in the MB area, 745 received CPR and 461 of these had a CA of presumed cardiac origin. Of these, 125 (27%) achieved sustained ROSC, 60 (13%) survived to 1 month, of whom 51 (11%) were discharged from hospital with a good neurological outcome (CPC ≤ 2), and 9 with a poor neurological outcome (CPC > 2).Compared with data from the 2000 to 2003 periods, survival increased from 5.6% to 13.01% (p < 0.0001). In the 2007–2011 group, low-flow time and bystander CPR were independent markers of survival.

Conclusions

OHCA survival has improved in our region. An increased bystander CPR rate associated with dispatcher-assisted CPR was the most significant cause of increased survival, but duration of CA remains critical for patient outcome.     

The cutoff values of intrathecal interleukin 8 and 6 for predicting the neurological outcome in cardiac arrest victims

Objectives

To evaluate the changes in inflammatory cytokines, such as interleukin (IL)-8 and IL-6, in the cerebrospinal fluid (CSF) and serum, and to identify any correlations with the neurological outcomes in patients resuscitated from cardiopulmonary arrest (CPA).

Materials and methods

This study was designed as a prospective clinical trial. Thirteen patients, who were resuscitated from out-of-hospital CPA and survived for more than 48 h, were enrolled in this study. Arterial blood was taken from the patients at 48 h after the return of spontaneous circulation (ROSC) and CSF was taken by lumbar puncture at the same time.

Results

In the CSF, the median levels of IL-8 and IL-6 in the patients resuscitated from CPA were significantly higher than those in the control subjects (1311 pg/ml vs 82 pg/ml, P < 0.001; 2040 pg/ml vs 1 pg/ml, P < 0.001, respectively). The Glasgow Outcome Scale (GOS) score evaluated at 6 months after the ROSC correlated significantly with the levels of IL-8 and IL-6. The cutoff values and sensitivity values with 100% specificity for the prediction of an unfavorable neurological outcome were 1423 pg/ml and 86% for IL-8, and 2708 pg/ml and 86% for IL-6, respectively.

Conclusion

We demonstrated the cutoff values of IL-8 and IL-6 in the CSF to predict the neurological outcome in the patients resuscitated from CPA. The excessive inflammatory cytokine reactions in the brain might therefore be related to the poor neurological outcome in patients with post-resuscitation encephalopathy.     

Duplex sonography of cerebral blood flow after cardiac arrest—A prospective observational study

Aim

Despite successful resuscitation, cardiac arrest (CA) often has a poor clinical prognosis. Different diagnostic tools have been established to predict patients’ outcome. However, their sensitivity remains low. Assessment of cerebral perfusion by duplex ultrasound might provide additional information regarding the extent of neuronal damage. The aim of the present study was to analyse the changes of global cerebral blood flow (CBF) and intracranial blood flow parameters in the acute stage after CA and its correlation with patients’ outcome.

Methods

We investigated 54 patients (17–85 years, mean age: 63 ± 17 years) after CA with return of spontaneous circulation on an intensive care unit. All patients received therapeutic hypothermia (TH) for 24 h after CA and reanimation. Serial measurements of CBF as well as intracranial blood flow velocities and pulsatility indices of the middle cerebral artery and the basal vein of Rosenthal were performed within the first 10 days using duplex ultrasound. Clinical outcome was measured using the Cerebral Performance Category.

Results

Measurements were successful in 53 patients. CBF values differed between 210 and 1100 ml/min. 24 patients (45%) attained a good outcome. No correlation between CBF or intracranial blood flow characteristics and outcome was found. Neither cerebral hypo- nor hyperperfusion was associated with a fatal outcome.

Conclusion

Cerebral perfusion varies widely after CA. Neither hypo- nor hyperperfusion seems to be an independent risk factor for poor outcome. Duplex ultrasound of cerebral haemodynamics after CA is suitable but probably of limited prognostic value.     

Survival after avalanche-induced cardiac arrest

Aim

Criteria to prolong resuscitation after cardiac arrest (CA) induced by complete avalanche burial are critical since profound hypothermia could be involved. We sought parameters associated with survival in a cohort of victims of complete avalanche burial.

Methods

Retrospective observational study of patients suffering CA on-scene after avalanche burial in the Northern French Alps between 1994 and 2013. Criteria associated with survival at discharge from the intensive care unit (ICU) were collected on scene and upon admission to Level-1 trauma center. Neurological outcome was assessed at 3 months using cerebral performance category score.

Results

Forty-eight patients were studied. They were buried for a median time of 43 min (25–76 min; 25–75th percentiles) and had a pre-hospital body core temperature of 28.0 °C (26.0–30.7). Eighteen patients (37.5%) had pre-hospital return of spontaneous circulation and 30 had refractory CA. Rewarming of 21 patients (43.7%) was performed using extracorporeal life support. Eight patients (16.7%) survived and were discharged from the ICU, three (6.3%) had favorable neurological outcome at 3 months. Pre-hospital parameters associated with survival were the presence of an air pocket and rescue collapse. On admission, survivors had lower serum potassium concentrations than non-survivors: 3.2 mmol/L (2.7–4.0) versus 5.6 mmol/L (4.2–8.0), respectively (P < 0.01). They also had normal values for prothrombin and activated partial thromboplastin compared to non-survivors.

Conclusions

Our findings indicate that survival after avalanche burial and on-scene CA is rarely associated with favorable neurological outcome. Among criteria associated with survival, normal blood coagulation on admission warrants further investigation.     

Serum S100B protein is associated with depressive symptoms in patients with end-stage renal disease

Objectives

Depression is associated with a poorer prognosis in patients with end-stage renal disease (ESRD). Increasing evidence indicates that glial pathology and blood–brain-barrier (BBB) dysfunction are involved in the pathophysiology of depression. S100B, a protein expressed in astro- and oligodendroglia in the human brain is considered a biomarker of depression. Our objective was to investigate the relationship between S100B and depressive symptoms in patients undergoing hemodialysis (HD).

Design and methods

Seventy-eight Korean patients undergoing chronic HD without significant neurological issues participated in a cross-sectional observation study. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), and serum S100B levels were measured using blood samples obtained prior to a mid-week HD session.

Results

The mean age of patients was 59.0 years, and the mean dialysis duration was 51.7 months. About 45% of patients undergoing HD met criteria for depression (BDI-II ≥ 20). Serum S100B levels were significantly higher in patients with depression compared with patients without depression (115.1 ± 45.4 vs. 66.1 ± 35.3 pg/mL, p < 0.001). S100B (r = 0.556, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP; r = 0.422, p < 0.001) and β2-microglobulin (r = 0.391, p < 0.001) levels were positively correlated with BDI-II scores. A multivariate regression analysis showed that both S100B and hs-CRP were significantly associated with BDI-II scores.

Conclusions

The results showed a close association between S100B and depressive symptoms in patients undergoing HD. However, the mechanisms underlying this relationship are currently unknown and warrant further investigation.     

The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest

Background

Brain injury is considered the main cause of death in patients who are hospitalized after cardiac arrest (CA). Induced hypothermia is recommended as neuroprotective treatment after (CA) but may affect prognostic parameters. We evaluated the effect of delayed neurological prognostication on the mode of death in hypothermia-treated CA-survivors.

Study design

Retrospective study at a Swedish university hospital, analyzing all in-hospital and out-of-hospital CA-patients treated with hypothermia during a 5-year period. Cause of death was categorized as brain injury, cardiac disorder or other. Multimodal neurological prognostication and decision on level of care was performed in comatose patients 72 h after rewarming. Neurological function was evaluated by Cerebral Performance Categories scale (CPC).

Results

Among 162 patients, 76 survived to hospital discharge, 65 of whom had a good neurological outcome (CPC 1–2), and 11 were severely disabled (CPC 3). No patient was in vegetative state. The cause of death was classified as brain injury in 61 patients, cardiac disorder in 14 and other in 11. Four patients were declared brain dead and became organ donors. They were significantly younger (median 40 years) and with long time to ROSC. Active intensive care was withdrawn in 50 patients based on a statement of poor neurological prognosis at least 72 h after rewarming. These patients died, mainly from respiratory complications, at a median 7 days after CA.

Conclusion

Following induced hypothermia and delayed neurological prognostication, brain injury remains the main cause of death after CA. Most patients with a poor prognosis statement died within 2 weeks.