Neurological pupil index and its association with other prognostic tools after cardiac arrest: A post hoc analysis.

INTRODUCTION: We evaluated the concordance of the Neurological pupil Index (NPi) with other predictors of outcome after cardiac arrest (CA). METHODS: Post hoc analysis of a prospective, international, multicenter study including adult CA patients. Predictors of unfavorable outcome (UO, Cerebral Performance Category of 3-5 at 3 months) included: a) worst NPi ≤ 2; b) presence of discontinuous encephalography (EEG) background; c) bilateral absence of N20 waves on somatosensory evoked potentials (N20ABS); d) peak neuron-specific enolase (NSE) blood levels > 60 mcg/L; e) myoclonus, which were all tested in a subset of patients who underwent complete multimodal assessment (MMM). RESULTS: A total of 269/456 (59 %) patients had UO and 186 (41 %) underwent MMM. The presence of myoclonus was assessed in all patients, EEG in 358 (78 %), N20 in 186 (41 %) and NSE measurement in 228 (50 %). Patients with discontinuous EEG, N20ABS or high NSE had a higher proportion of worst NPi ≤ 2. The accuracy for NPi to predict a discontinuous EEG, N20ABS, high NSE and the presence of myoclonus was moderate. Concordance with NPi ≤ 2 was high for NSE, and moderate for discontinuous EEG and N20ABS. Also, the higher the number of concordant predictors of poor outcome, the lower the observed NPi. CONCLUSIONS: In this study, NPi ≤ 2 had moderate to high concordance with other unfavorable outcome prognosticators of hypoxic-ischemic brain injury. This indicates that NPi measurement could be considered as a valid tool for coma prognostication after cardiac arrest.

Cerebral Microdialysis-Based Interventions Targeting Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI), a complication of subarachnoid hemorrhage (SAH), is linked to cerebral vasospasm and associated with poor long-term outcome. We implemented a structured cerebral microdialysis (CMD) based protocol using the lactate/pyruvate ratio (LPR) as an indicator of the cerebral energy metabolic status in the neurocritical care decision making, using an LPR ≥ 30 as a cutoff suggesting an energy metabolic disturbance. We hypothesized that CMD monitoring could contribute to active, protocol-driven therapeutic interventions that may lead to the improved management of patients with SAH. METHODS: Between 2018 and 2020, 49 invasively monitored patients with SAH, median Glasgow Coma Scale 11 (range 3-15), and World Federation of Neurosurgical Societies scale 4 (range 1-5) on admission receiving CMD were included. We defined a major CMD event as an LPR ≥ 40 for ≥ 2 h and a minor CMD event as an LPR ≥ 30 for ≥ 2 h. RESULTS: We analyzed 7,223 CMD samples over a median of 6 days (5-8). Eight patients had no CMD events. In 41 patients, 113 minor events were recorded, and in 23 patients 42 major events were recorded. Our local protocols were adhered to in 40 major (95%) and 98 minor events (87%), with an active intervention in 32 (76%) and 71 (63%), respectively. Normalization of energy metabolic status (defined as four consecutive samples with LPR < 30 for minor and LPR < 40 for major events) was seen after 69% of major and 59% of minor events. The incidence of DCI-related infarcts was 10% (five patients), with only two observed in a CMD-monitored brain region. CONCLUSIONS: Active interventions were initiated in a majority of LPR events based on CMD monitoring. A low DCI incidence was observed, which may be associated with the active interventions. The potential aid of CMD in the clinical decision-making targeting DCI needs confirmation in additional SAH studies.

Central venous catheter-related complications in hematologic patients: An observational study.

BACKGROUND: The frequency of central venous catheter (CVC)-related complications in hematologic patients has previously been studied but some uncertainty remains. Therefore, this observational cohort study was designed primarily to investigate mechanical and infectious complications related to CVC insertion in hematologic patients and secondarily to identify factors associated with these complications. METHODS: Documented data on CVC insertions in all adult hematologic patients who received a CVC from 2013 to 2019 at a University Hospital in Sweden were retrospectively collected. RESULTS: A total of 589 CVC insertions in 387 patients were included. The prevalence of moderate and severe mechanical complications, predominantly comprising grades 2-4 bleeding, was 11%. Preprocedural coagulopathy, number of needle passes, and arterial puncture were all independently associated with grades 2-4 bleeding. The incidence of suspected catheter-related infections (sCRI) was 3.7/1000 catheter days. Higher body mass index and male gender were independently associated with sCRI. CONCLUSIONS: Patients with hematologic malignancies have a high risk of both grades 2-4 bleeding and sCRI after CVC insertion. This underlines the importance of optimizing the conditions at the insertion and also of daily inspections, evaluation of future needs, and extra precautions to avoid sCRI in these susceptible patients.

Postanoxic electrographic status epilepticus and serum biomarkers of brain injury.

AIM: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. METHODS: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. RESULTS: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. CONCLUSION: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.

Cardiac output during targeted temperature management and renal function after out-of-hospital cardiac arrest.

PURPOSE: After resuscitation from out-of-hospital cardiac arrest (OHCA), renal injury and hemodynamic instability are common. We aimed to assess the association between low cardiac output during targeted temperature management (TTM) and acute kidney injury (AKI) after OHCA. MATERIALS AND METHODS: Single-center substudy of 171 patients included in the prospective, randomized TTM-trial. Hemodynamic evaluation was performed with serial measurements by pulmonary artery catheter. AKI was the primary endpoint and was defined according to the KDIGO-criteria. RESULTS: Of 152 patients with available hemodynamic data, 49 (32%) had AKI and 21 (14%) had AKI with need for renal replacement therapy (RRT) in the first three days. During targeted temperature management, patients with AKI had higher heart rate (11 beats/min, pgroup < 0.0001), higher mean arterial pressure (MAP) (4 mmHg, pgroup = 0.001) and higher lactate (1 mmol/L, pgroup < 0.0001) compared to patients without AKI. However, there was no difference in cardiac index (pgroup = 0.25). In a multivariate logistic regression model, adjusting for potential confounders, MAP (p = .03), heart rate (p = .01) and lactate (p = .006), but not cardiac output, were independently associated with AKI. CONCLUSIONS: Blood pressure, heart rate and lactate, but not cardiac output, during 24 h of TTM were associated with AKI in comatose OHCA-patients.

Renal function after out-of-hospital cardiac arrest; the influence of temperature management and coronary angiography, a post hoc study of the target temperature management trial.

BACKGROUND: To elucidate the incidence of acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) and to examine the impact of target temperature management (TTM) and early coronary angiography on renal function. METHODS: Post hoc analysis of the TTM trial, a multinational randomised controlled trial comparing target temperature of 33 °C versus 36 °C in patients with return of spontaneous circulation after OHCA. The impact of TTM and early angiography (within 6 h of OHCA) versus late or no angiography on the development of AKI during the 7-day period after OHCA was analysed. AKI was defined according to modified KDIGO criteria in patients surviving beyond day 2 after OHCA. RESULTS: Following exclusions, 853 of 939 patients enrolled in the main trial were analysed. Unadjusted analysis showed that significantly more patients in the 33 °C group had AKI compared to the 36 °C group [211/431 (49%) versus 170/422 (40%) p = 0.01], with a worse severity (p = 0.018). After multivariable adjustment, the difference was not significant (odds ratio 0.75, 95% confidence interval 0.54-1.06, p = 0.10]. Five hundred seventeen patients underwent early coronary angiography. Although the unadjusted analysis showed less AKI and less severe AKI in patients who underwent early angiography compared to patients with late or no angiography, in adjusted analyses, early angiography was not an independent risk factor for AKI (odds ratio 0.73, 95% confidence interval 0.50-1.05, p = 0.09). CONCLUSIONS: In OHCA survivors, TTM at 33 °C compared to management at 36 °C did not show different rates of AKI and early angiography was not associated with an increased risk of AKI. TRIAL REGISTRATION: NCT01020916 . Registered on www.ClinicalTrials.gov 26 November 2009 (main trial).

The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest.

BACKGROUND: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. METHODS: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. RESULTS: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. CONCLUSIONS: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.

Bleeding Complications After Cardiac Arrest and Targeted Temperature Management, a Post Hoc Study of the Targeted Temperature Management Trial.

Target Temperature Management (TTM) is standard care following out of hospital cardiac arrest (OHCA). The aim of the study was to evaluate if treatment temperature (33°C or 36°C) or other predefined variables were associated with the occurrence of bleeding in the TTM study. This study is a predefined, post hoc analysis of the TTM trial, a multinational randomized controlled trial comparing treatment at 33°C and 36°C for 24 hours after OHCA with return of spontaneous circulation. Bleeding events from several locations were registered daily. The main outcome measure was occurrence of any bleeding during the first 3 days of intensive care. Risk factors for bleeding, including temperature allocation, were evaluated. Complete data were available for 722/939 patients. Temperature allocation was not associated with bleeding either in the univariable (p = 0.95) or in the primary multivariable analysis (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.64-1.41, p = 0.80). A multiple imputation model, including all patients, was used as a sensitivity analysis, rendering similar results (OR 0.98; 95% CI 0.69-1.38, p = 0.92). Factors associated with bleeding were increasing age, female sex, and angiography with percutaneous coronary intervention (PCI) within 36 hours of cardiac arrest (CA) in both the primary and the sensitivity analysis. TTM at 33°C, when compared to TTM at 36°C, was not associated with an increased incidence of bleeding during the first 3 days of intensive care after CA. Increasing age, female gender, and PCI were independently associated with any bleeding the first 3 days after CA.

Mean arterial pressure during targeted temperature management and renal function after out-of-hospital cardiac arrest.

PURPOSE: This study investigates the association between mean arterial pressure (MAP) and renal function after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: Post-hoc analysis of 851 comatose OHCA-patients surviving >48 h included in the targeted temperature management (TTM)-trial. RESULTS: Patients were stratified by mean MAP during TTM in the following groups; <70 mmHg (22%), 70-80 mmHg (43%), and > 80 mmHg (35%). Median (interquartile range) eGFR (ml/min/1.73 m2) 48 h after OHCA was inversely associated with MAP-group (70 (47-102), 84 (56-113), 94 (61-124), p < .001, for the <70-group, 70-80-group and > 80-group respectively). After adjusting for potential confounders, in a mixed model including eGFR after 1, 2 and 3 days this association remained significant (pgroup_adjusted = 0.0002). Higher mean MAP was independently associated with lower odds of renal replacement therapy (odds ratioadjusted = 0.77 [95% confidence interval, 0.65-0.91] per 5 mmHg increase; p = .002]). CONCLUSIONS: Low mean MAP during TTM was independently associated with decreased renal function and need of renal replacement therapy in a large cohort of comatose OHCA-patients. Increasing MAP above the recommended 65 mmHg could potentially be renal-protective. This hypothesis should be investigated in prospective trials.

Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study.

PURPOSE: To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA). METHODS: We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)-blinded to clinicians and outcome assessors-were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1-2: full recovery or moderate disability) versus unfavorable outcome (CPC 3-5: severe disability, vegetative state, or death). RESULTS: At any time between day 1 and 3, an NPi ≤ 2 (n = 456 patients) had a 51% (95% CI 49-53) negative predictive value and a 100% positive predictive value [PPV; 0% (0-2) false-positive rate], with a 100% (98-100) specificity and 32% (27-38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p  < 0.001 at day 1 and 2; p  = 0.06 at day 3). The combination of NPi ≤ 2 with bilaterally absent somatosensory evoked potentials (SSEP; n = 188 patients) provided higher sensitivity [58% (49-67) vs. 48% (39-57) for SSEP alone], with comparable specificity [100% (94-100)]. CONCLUSIONS: Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.

Electroencephalographic characteristics of status epilepticus after cardiac arrest.

OBJECTIVE: To describe the electrophysiological characteristics and pathophysiological significance of electrographic status epilepticus (ESE) after cardiac arrest and specifically compare patients with unequivocal ESE to patients with rhythmic or periodic borderline patterns defined as possible ESE. METHODS: Retrospective cohort study of consecutive patients treated with targeted temperature management and monitored with simplified continuous EEG. Patients with ESE were identified and electrographically characterised until 72h after ESE start using the standardised terminology of the American Clinical Neurophysiology Society. RESULTS: ESE occurred in 41 of 127 patients and 22 fulfilled the criteria for unequivocal ESE, which typically appeared early and transiently. Three of the four survivors had unequivocal ESE, starting after rewarming from a continuous background. There were no differences between the groups of unequivocal ESE and possible ESE regarding outcome, neuron-specific enolase levels or prevalence of reported clinical convulsions. CONCLUSION: ESE is common after cardiac arrest. The distinction between unequivocal and possible ESE patterns was not reflected by differences in clinical features or survival. SIGNIFICANCE: A favourable outcome is seen infrequently in patients with ESE, regardless of using strict or liberal ESE definitions.

The Combination of Biomarkers for Prognostication of Long-Term Outcome in Patients Treated with Mild Hypothermia After Out-of-Hospital Cardiac Arrest-A Pilot Study.

To explore if the brain biomarker neuron-specific enolase (NSE) in combination with a biomarker for stress; CT-proAVP (copeptin), oxidation; peroxiredoxin 4 (Prx4), inflammation; procalcitonin (PCT), or with biomarkers from the heart; midregional proatrial natriuretic peptide (MR-proANP), or troponin T (TnT) can improve the prognostic accuracy of long-term outcome after out-of-hospital cardiac arrest (OHCA). Serum samples from cardiac arrest patients, treated at 33°C for 24 hours, were collected serially at 12, 24, and 48 hours after cardiac arrest. The concentration of the investigated biomarkers was measured using stored samples, and long-term outcome was evaluated by the cerebral performance category (CPC) at 6 months. Poor outcome was defined as CPC 3-5. Sixty-two patients with OHCA of presumed cardiac cause were included. NSE had best prognostic accuracy for poor outcome at 48 hours with a receiver operating characteristic area under curve (AUC) of 0.94 (95% confidence interval [CI] 0.87-1). The combination of NSE with TnT, both at 48 hours, increased the AUC to 0.98 (95% CI 0.95-1, likelihood ratio [LR] test p-value 0.07, net reclassification index [NRI] <0.001); NSE and MR-proANP, both at 12 hours, yielded an AUC of 0.91 (95% CI 0.80-1, LR test p-value 0.0014, NRI p-value 0.003); NSE at 48 hours with MR-proANP at 12 hours yielded an AUC of 0.97 (95% CI 0.92-1, LR test p-value 0.055, NRI p-value 0.04). This pilot study suggests that a combination of biomarkers with NSE could be beneficial for improving early prognostication of long-term outcome following OHCA.

Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study.

BACKGROUND: This porcine study was designed to explore the effects of repetitive intravenous adrenaline doses on physiologic parameters during CPR. METHODS: Thirty-six adult pigs were randomised to four injections of: adrenaline 0.02 mg(kgdose)(-1), adrenaline 0.03 mg(kgdose)(-1) or saline control. The effect on systolic, diastolic and mean arterial blood pressure, cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), arterial oxygen saturation via pulse oximetry (SpO2), cerebral tissue oximetry (SctO2), were analysed immediately prior to each injection and at peak arterial systolic pressure and arterial blood gases were analysed at baseline and after 15 min. RESULT: In the group given 0.02 mg(kgdose)(-1), there were increases in all arterial blood pressures at all 4 pressure peaks but CePP only increased significantly after peak 1. A decrease in ETCO2 following peak 1 and 2 was observed. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg(kgdose)(-1), all ABP's increased at the first 4 pressure peaks but CePP only following 3 pressure peaks. Lower ETCO2, SctO2 and SpO2 were seen at peak 1 and beyond. In the two adrenaline groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to the control. CONCLUSION: Repetitive intravenous adrenaline doses increased ABP's and to some extent also CePP, but significantly decreased organ and brain perfusion. The institutional protocol number: Malmö/Lund Committee for Animal Experiment Ethics, approval reference number: M 192-10.

Mechanical chest compressions in the coronary catheterization laboratory to facilitate coronary intervention and survival in patients requiring prolonged resuscitation efforts.

BACKGROUND: Resuscitation after cardiac arrest (CA) in the catheterization laboratory (cath-lab) using mechanical chest compressions (CC) during simultaneous percutaneous coronary intervention (PCI) is a strong recommendation in the 2015 European Resuscitation Council (ERC) guidelines. This study aimed at re-evaluating survival to hospital discharge and assess long term outcome in this patient population. METHODS: Patients presenting at the cath lab with spontaneous circulation, suffering CA and requiring prolonged mechanical CC during cath lab procedures between 2009 and 2013 were included. Circumstances leading to CA, resuscitation parameters and outcomes were evaluated within this cohort. For comparison, patients needing prolonged manual CC in the cath lab in the pre-mechanical CC era were evaluated. Six-month and one year survival with a mechanical CC treatment strategy from 2004 to 2013 was also evaluated. RESULTS: Thirty-two patients were included between 2009 and 2013 (24 ST-elevation myocardial infarction (STEMI), 4 non-STEMI, 2 planned PCI, 1 angiogram and 1 intra-aortic counter pulsation balloon pump insertion). Twenty were in cardiogenic shock prior to inclusion. Twenty-five were successfully treated with PCI. Median mechanical CC duration for the total cohort (n = 32) was 34 min (range 5-90), for the 15 patients with circulation discharged from the cath-lab, 15 min (range 5-90), and for the eight discharged alive from hospital, 10 min (range 5-52). Twenty-five percent survived with good neurological outcome at hospital discharge. Ten patients treated with manual CC were included with one survivor. DISCUSSION: Eighty-seven percent of the patients included in the mechanical CC cohort had their coronary or cardiac intervention performed during mechanical CC with an 80 % success rate. This shows that the use of mechanical CC during an intervention does not seem to impair the interventional result substantially. The survival rate after one year was 87 %. CONCLUSIONS: Among patients suffering CA treated with mechanical CC in the cath-lab, 25% had a good neurological outcome at hospital discharge compared to 10% treated with manual CC. Long term survival in patients discharged from hospital is good.

Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest.

BACKGROUND: Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers. METHODS: In this retrospective single study, we analyzed consecutive patients who suffered from CA, and who received temperature management and were monitored with simplified continuous EEG (cEEG) during a five-year period. The patients' charts and cEEG data were initially screened to identify patients with clinical seizures or ESE. The cEEG diagnosis of ESE was retrospectively reanalyzed according to strict criteria by a neurophysiologist blinded to patient outcome. The EEG background patterns prior to the onset of ESE, duration of ESE, presence of clinical seizures, and use of antiepileptic drugs were analyzed. The results of somatosensory-evoked potentials (SSEPs) and neuron-specific enolase (NSE) at 48 h after CA were described in all patients with ESE. Antiepileptic treatment strategies were not protocolized. Outcome was evaluated using the Cerebral Performance Category (CPC) scale at 6 months, and good outcome was defined as CPC 1-2. RESULTS: Of 127 patients, 41 (32%) developed ESE. Twenty-five patients had a discontinuous EEG background prior to ESE, and all died without regaining consciousness. Sixteen patients developed a continuous EEG background prior to the start of ESE, four of whom survived, three with CPC 1-2 and one with CPC 3 at 6 months. Among survivors, ESE developed at a median of 46 h after CA. All had preserved N20 peaks on SSEP and NSE values of 18-37 µg/l. CONCLUSION: Electrographic status epilepticus is common among comatose patients after cardiac arrest, with few survivors. A combination of a continuous EEG background prior to ESE, preserved N20 peaks on SSEPs, and low or moderately elevated NSE levels may indicate a good outcome. This article is part of a Special Issue entitled "Status Epilepticus".

The inflammatory marker suPAR after cardiac arrest.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is released in response to inflammatory stimuli, and plasma levels are associated with long-term outcomes. The ischemia/reperfusion injury caused by cardiac arrest (CA) and resuscitation triggers an inflammatory response. This pilot study aimed at investigating suPAR levels in relation to outcome after CA and mild induced hypothermia. METHODS: suPAR levels were measured at 6, 36, and 72 hours in patients treated with hypothermia after CA. suPAR levels were analyzed in relation to survival after 6 months. Receiver operating characteristic curve (ROC)-analyses were performed, and area under the curve (AUC) was calculated. Time to return of spontaneous circulation (ROSC) was correlated to suPAR levels. RESULTS: Fifty-five patients (40 male, median 65 years) were included, and 33 (60%) were alive after 6 months. The suPAR levels were significantly higher in nonsurviving patients compared with survivors at 6 and 36 hours (p=0.006 and 0.034 respectively), but not at 72 hours. The suPAR levels increased from 6 to 72 hours (p<0.0001). Time to ROSC correlated positively with suPAR levels at 6 hours (p=0.003) but not at 36 and 72 hours. ROC analysis shoved an AUC of 0.76 at 6 hours. In the subgroup of CA of cardiac cause, the AUC was 0.84. CONCLUSION: suPAR levels at 6 and 36 hours after CA were significantly higher in nonsurviving patients compared with survivors; however, the overlap in suPAR levels between the outcome groups was substantial, reducing the prognostic value. There was a significant increase in suPAR levels during the first 72 hours after CA.

Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C.

BACKGROUND: Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general. METHODS AND RESULTS: Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar. CONCLUSIONS: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01946932.

Repeated epinephrine doses during prolonged cardiopulmonary resuscitation have limited effects on myocardial blood flow: a randomized porcine study.

BACKGROUND: In current guidelines, prolonged cardiopulmonary resuscitation (CPR) mandates administration of repeated intravenous epinephrine (EPI) doses. This porcine study simulating a prolonged CPR-situation in the coronary catheterisation laboratory, explores the effect of EPI-administrations on coronary perfusion pressure (CPP), continuous coronary artery flow average peak velocity (APV) and amplitude spectrum area (AMSA). METHODS: Thirty-six pigs were randomized 1:1:1 to EPI 0.02 mg/kg/dose, EPI 0.03 mg/kg/dose or saline (control) in an experimental cardiac arrest (CA) model. During 15 minutes of mechanical chest compressions, four EPI/saline-injections were administered, and the effect on CPP, APV and AMSA were recorded. Comparisons were performed between the control and the two EPI-groups and a combination of the two EPI-groups, EPI-all. RESULT: Compared to the control group, maximum peak of CPP (Pmax) after injection 1 and 2 was significantly increased in the EPI-all group (p = 0.022, p = 0.016), in EPI 0.02-group after injection 2 and 3 (p = 0.023, p = 0.027) and in EPI 0.03-group after injection 1 (p = 0.013). At Pmax, APV increased only after first injection in both the EPI-all and the EPI 0.03-group compared with the control group (p = 0.011, p = 0.018). There was no statistical difference of AMSA at any Pmax. Seven out of 12 animals (58%) in each EPI-group versus 10 out of 12 (83%) achieved spontaneous circulation after CA. CONCLUSION: In an experimental CA-CPR pig model repeated doses of intravenous EPI results in a significant increase in APV only after the first injection despite increments in CPP also during the following 2 injections indicating inappropriate changes in coronary vascular resistance during subsequent EPI administration.

Serum neuron specific enolase - impact of storage and measuring method.

BACKGROUND: Neuron specific enolase (NSE) is a recognized biomarker for assessment of neurological outcome after cardiac arrest, but its reliability has been questioned. Our aim was to investigate what influence storage of samples and choice of measuring methods may have on levels of NSE in peripheral blood. METHODS: Two serum samples were drawn simultaneously from 51 hypothermia treated cardiac arrest patients. One sample (original sample) was analysed when collected, using the Diasorin-method (LIAISON®NSE, LNSE). The other sample was frozen, stored at -70°C (stored sample), and reanalysed in the same laboratory 4-7 years later using both the Diasorin method and a Roche-method (NSE Cobas e601, CNSE). In addition, a comparison of the two methods was performed on 29 fresh samples. RESULTS: The paired NSE results in original and stored samples were not significantly different, using the LNSE-method. The two methods produced significantly different results (p < 0.0001) on the paired, stored samples, with the CNSE method yielding higher values than the LNSE-method in 96% of samples. The CNSE method resulted in 36% higher values on average. In the method comparison on fresh samples, the CNSE-method generated on average 15% higher values compared to the LNSE-method, and the difference between the paired results was significant (p < 0.0001). CONCLUSION: The CNSE method generated consistently higher NSE-values than the LNSE method and this difference was more pronounced when frozen samples were analysed. Tolerability for prolonged freezing was acceptable.