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Background Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated. Methods Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE). Results Total of 2113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n = 940, 44.5%), shockable/no STE (Sh-NST) (n = 716, 33.9%), nonshockable/STE (Nsh-ST) (n = 110, 5.2%), and shockable/STE (Sh-ST) (n = 347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST. Conclusions Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation. Brief abstract Out of hospital cardiac arrest (OHCA) survivors with ST elevation and/or shockable rhythms benefit from coronary angiography and revascularization. Nonshockable cardiac arrest survivors with no ST elevation have the worst prognosis and rarely undergo coronary angiography. Nonshockable rhythms with no ST elevation was the most common presentation after OHCA and among a small subgroup underwent coronary angiography, 1 in 4 patients with had culprit lesion and underwent revascularization. Coronary angiography was associated with high prevalence of acute culprit coronary lesions and should be considered for those with a probably cardiac cause for their arres.

Introduction Low socioeconomic status has been associated with worse outcome after cardiac arrest. This study aims to investigate if patients´ income influences the probability to receive early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients. Methods In this nationwide retrospective observational study, 3906 OHCA patients admitted alive and registered in the Swedish Registry for Cardiopulmonary Resuscitation were included. Individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from SWEDEHEART and other national registers. Results Patients were divided into quarters depending on their income level. In the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where 35.5% of patients in the highest income quarters received early angiography compared to 15.4% in the lowest income quarters. When adjusting for educational level, sex, age, comorbidity and hospital type, there were still higher chance of receiving early coronary angiography with increasing income, OR 1.31 (CI 1.01–1.68) and 1.67 (CI 1.29–2.16) for the two highest income quarters respectively compared to the lowest income quarter. When adding potential mediators to the model (first recorded ECG rhythm by the EMS, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. The main mediator was first recorded ECG rhythm. Conclusion Income level is associated with the probability to undergo early coronary angiography in OHCA patients. This association seems to be mediated by the initial ECG rhythm.

Introduction We investigated the impact of gender in performance and findings of early coronary angiography (CAG) and percutaneous coronary intervention (PCI), comorbidity and outcome in a large population of out-of-hospital cardiac arrest (OHCA) patients with an initially shockable rhythm. Methods Retrospective cohort study. Data retrieved 2008–2013 from the Swedish Register for Cardio-Pulmonary Resuscitation, Swedeheart Registry and National Patient Register. Results We identified 1498 patients of whom 78% were men. Men and women had the same pathology on the first registered electrocardiogram (ECG): 30% vs. 29% had ST-elevation and 10% vs. 9% had left bundle branch block (LBBB) (P = 0.97). Proportions of performed CAG did not differ between genders. Among patients without ST-elevation/LBBB men more often had at least one significant stenosis, 78% vs. 54% (P = 0.001), more multi-vessel disease (P = 0.01), had normal coronary angiography less often, 22% vs. 46% and PCI more often, 59% vs. 42% (P = 0.03). Among patients without ST-elevation/LBBB on the initial ECG, more men had previously known ischaemic heart disease, 27% vs. 19% (P = 0.02) and a presumed cardiac origin of the cardiac arrest, 86% vs. 72% (P Conclusion Despite no gender differences in ECG findings indicating an early CAG, men had more severe coronary artery disease while women more frequently had normal coronary angiography. However, this did not influence 1-year survival.

Background: In out-of-hospital cardiac arrest, chest compression–only cardiopulmonary resuscitation (CO-CPR) has emerged as an alternative to standard CPR (S-CPR), using both chest compressions and rescue breaths. Since 2010, CPR guidelines recommend CO-CPR for both untrained bystanders and trained bystanders unwilling to perform rescue breaths. The aim of this study was to describe changes in the rate and type of CPR performed before the arrival of emergency medical services (EMS) during 3 consecutive guideline periods in correlation to 30-day survival. Methods: All bystander-witnessed out-of-hospital cardiac arrests reported to the Swedish register for cardiopulmonary resuscitation in 2000 to 2017 were included. Nonwitnessed, EMS-witnessed, and rescue breath–only CPR cases were excluded. Patients were categorized as receivers of no CPR (NO-CPR), S-CPR, or CO-CPR before EMS arrival. Guideline periods 2000 to 2005, 2006 to 2010, and 2011 to 2017 were used for comparisons over time. The primary outcome was 30-day survival. Results: A total of 30 445 patients were included. The proportions of patients receiving CPR before EMS arrival changed from 40.8% in the first time period to 58.8% in the second period, and to 68.2% in the last period. S-CPR changed from 35.4% to 44.8% to 38.1%, and CO-CPR changed from 5.4% to 14.0% to 30.1%, respectively. Thirty-day survival changed from 3.9% to 6.0% to 7.1% in the NO-CPR group, from 9.4% to 12.5% to 16.2% in the S-CPR group, and from 8.0% to 11.5% to 14.3% in the CO-CPR group. For all time periods combined, the adjusted odds ratio for 30-day survival was 2.6 (95% CI, 2.4–2.9) for S-CPR and 2.0 (95% CI, 1.8–2.3) for CO-CPR, in comparison with NO-CPR. S-CPR was superior to CO-CPR (adjusted odds ratio, 1.2; 95% CI, 1.1–1.4). Conclusions: In this nationwide study of out-of-hospital cardiac arrest during 3 periods of different CPR guidelines, there was an almost a 2-fold higher rate of CPR before EMS arrival and a concomitant 6-fold higher rate of CO-CPR over time. Any type of CPR was associated with doubled survival rates in comparison with NO-CPR. These findings support continuous endorsement of CO-CPR as an option in future CPR guidelines because it is associated with higher CPR rates and overall survival in out-of-hospital cardiac arrest.

Background The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the ‘DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest’ (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods Resuscitated bystander witnessed OHCA patients >18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.

Background Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. Methods Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. Results There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. Conclusions Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.

BACKGROUND: Acute kidney Injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID-19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk. METHODS: In a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM-1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP-2) were analysed in 52 patients at admission. RESULTS: The majority (n=51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n=37, 65%) while stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30-day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n=9 (17%) patients. CONCLUSIONS: A majority of patients with COVID-19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.

The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.Seven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH 7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted 40% survival. Presence of the 3 strongest risk factors (age85 years, time-to-ROSC30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.Patients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.

Aim Strategies to increase provision of bystander CPR include mass education of laypersons. Additionally, programs directed at emergency dispatchers to provide CPR instructions during emergency calls to untrained bystanders have emerged. The aim of this study was to evaluate the association between dispatcher-assisted CPR (DA- CPR) and 30-day survival compared with no CPR or spontaneously initiated CPR by lay bystanders prior to emergency medical services in out of hospital cardiac arrest (OHCA). Methods Nationwide observational cohort study including all consecutive lay bystander witnessed OHCAs reported to the Swedish Register for Cardiopulmonary Resuscitation in 2010–2017. Exposure was categorized as: no CPR (NO-CPR), DA-CPR and spontaneously initiated CPR (SP-CPR) prior to EMS arrival. Propensity-score matched cohorts were used for comparison between groups. Main Outcome was 30-day survival. Results A total of 15 471 patients were included and distributed as follows: NO-CPR 6440 (41.6%), DA-CPR 4793 (31.0%) and SP-CPR 4238 (27.4%). Survival rates to 30 days were 7.1%, 13.0% and 18.3%, respectively. In propensity-score matched analysis (DA-CPR as reference), NO-CPR was associated with lower survival (conditional OR 0.61, 95% CI 0.52–0.72) and SP-CPR was associated with higher survival (conditional OR 1.21 (95% CI 1.05–1.39). Conclusions DA-CPR was associated with a higher survival compared with NO-CPR. However, DA-CPR was associated with a lower survival compared with SP-CPR. These results reinforce the vital role of DA-CPR, although continuous efforts to disseminate CPR training must be considered a top priority if survival after out of hospital cardiac arrest is to continue to increase.

Background: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment–elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways. Methods: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system. Results: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83–4.49; P ≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10–2.77; P=0.017), initial ejection fractionP =0.002), shock at presentation (OR, 2.27; CI, 1.42–3.62; P25 minutes (OR, 1.42; CI, 0.90–2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. Conclusions: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment–elevation myocardial infarction at the point of care.

There is limited knowledge about the long-term effects on pulmonary function of COVID-19 in patients that required intensive care treatment. Spirometry and diffusing capacity for carbon monoxide (DLCO) were measured in 60 subjects at 3-6 months post discharge. Impaired lung function was found in 52% of the subjects, with reduced DLCO as the main finding. The risk increased with age above 60 years, need for mechanical ventilation and longer ICU stay as well as lower levels of C-reactive protein at admission. This suggests the need of follow-up with pulmonary function testing in intensive-care treated patients.

Introduction The relations between specific ECG patterns and coronary angiographic findings in cardiac arrest patients with different comorbidities are not properly assessed. More evidence is needed to identify patients with the highest risk for acute coronary artery disease as a cause of the cardiac arrest. This study aims to describe the coronary artery findings after cardiac arrest in relation to ECG and comorbidity. Method A retrospective study of out-of-hospital cardiac arrest patients, with coronary angiography performed within 28 days. ECG on admission, comorbidity, PCI attempts and angiographic findings are described. Data were retrieved from national registries in Sweden. Results Among 1133 patients with available ECG and angiography information the mean age was 64 years. The rate of shockable rhythm was 79%. The total incidence of any significant stenosis in cardiac arrest patients without ST-elevation who underwent coronary angiography within 28 days was 71%. The incidence of any stenosis in patients with normal ECG was 62.1% and in patients with LBBB, 59.3%. In patients with ST-depression or RBBB, PCI attempts were made in 47.1% and 42.4% respectively, compared with 33.3% in patients with normal ECG. Among patients without ST-elevation, those with diabetes mellitus and those with initial shockable rhythm respectively, 84.8% and 71.5 had at least one significant stenosis. Conclusion Our study suggests, that evaluation of ECG patterns and comorbidities in out-of-hospital cardiac arrest patients without ST-segment elevation may be important to identify those with a high risk of coronary artery lesions that could benefit from early revascularization.

The aim of this review is to update and discuss the use of mechanical chest compression devices in treatment of cardiac arrest.Three recently published large multicenter randomized trials have not been able to show any improved outcome in adult out-of-hospital cardiac arrest patients when compared with manual chest compressions.Mechanical chest compression devices have been developed to better deliver uninterrupted chest compressions of good quality. Prospective large randomized studies have not been able to prove a better outcome compared to manual chest compressions; however, latest guidelines support their use when high-quality manual chest compressions cannot be delivered. Mechanical chest compressions can also be preferred during transportation, in the cath-lab and as a bridge to more invasive support like extracorporeal membrane oxygenation.

We studied resuscitation process metrics in patients with out-of-hospital cardiac arrest enrolled in a randomized trial comparing one protocol designed to best use a mechanical CPR device, with another based on the 2005 European Resuscitation Council guidelines for manual CPR.We analyzed clinical data, ECG signals, and transthoracic impedance signals for a subset of the patients in the LUCAS in Cardiac Arrest (LINC) trial, including 124 patients randomized to mechanical and 82 to manual CPR. Chest compression fraction (CCF) was defined as the fraction of time during cardiac arrest that chest compressions were administered.Patients in the mechanical CPR group had a higher CCF than those in the manual CPR group [0.84 (0.78, 0.91) vs. 0.79 (0.70, 0.86), p0.001]. The median duration of their pauses for defibrillation was also shorter [0 s (0, 6.0) vs. 10.0 s (7.0, 14.3), p0.001]. Compressions were interrupted for a median of 36.0 s to apply the compression device. There was no difference between groups in duration of the longest pause in compressions [32.5s vs. 26.0 s, p = 0.24], number of compressions received per minute [86.5 vs. 88.3, p = 0.47], defibrillation success rate [73.2% vs. 81.0%, p = 0.15], or refibrillation rate [74% vs. 77%, p = 0.79].A protocol using mechanical chest compression devices reduced interruptions in chest compressions, and enabled defibrillation during ongoing compressions, without adversely affecting other resuscitation process metrics. Future emphasis on optimizing device deployment may be beneficial.

To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care.

Cardiopulmonary resuscitation is started in 5000 victims of out-of-hospital cardiac arrest in Sweden each year and the survival rate is approximately 10%. The subsequent development of a global ischaemic brain injury is the major determinant of the neurological prognosis for those patients who reach the hospital alive. Induced hypothermia is a recommended treatment after cardiac arrest and has been implemented in most Swedish hospitals. Recent studies indicate that induced hypothermia may affect neurological prognostication and previous international recommendations are therefore no longer valid when hypothermia is applied. An expert group from the Swedish Resuscitation Council has reviewed the literature and made recommendations taking into account the effects of induced hypothermia and concomitant sedation. A delayed neurological evaluation at 72 h after rewarming is recommended for hypothermia treated patients. This evaluation should be based on several independent methods and the possibility of lingering pharmacological effects should be considered.

The LINC trial evaluated two ALS-CPR algorithms for OHCA patients, consisting of 3min' mechanical chest compression (LUCAS) cycles with defibrillation attempt through compressions vs. 2min' manual compressions with compression pause for defibrillation. The PARAMEDIC trial, using 2min' algorithm found worse outcome for patients with initial VF/VT in the LUCAS group and they received more adrenalin compared to the manual group. We wanted to evaluate if these algorithms had any outcome effect for patients still in VF/VT after the initial defibrillation and how adrenalin timing impacted it.Both groups received manual chest compressions first. Based on non-electronic CPR process documentation, outcome, neurologic status and its relation to CPR duration prior to the first detected return of spontaneous circulation (ROSC), time to defibrillation and adrenalin given were analysed in the subgroup of VF/VT patients.Seven hundred and fifty-seven patients had still VF/VT after initial chest compressions combined with a defibrillation attempt (374 received mechanical CPR) or not (383 received manual CPR). No differences were found for ROSC (mechanical CPR 58.3% vs. manual CPR 58.6%, p=0.94), or 6-month survival with good neurologic outcome (mechanical CPR 25.1% vs. manual CPR 23.0%, p=0.50). A significant difference was found regarding the time from start of manual chest compression to the first defibrillation (mechanical CPR: 4 (2-5) min vs manual CPR 3 (2-4) min, P0.001). The time from the start of manual chest compressions to ROSC was longer in the mechanical CPR group.No difference in short- or long-term outcomes was found between the 2 algorithms for patients still in VF/VT after the initial defibrillation. The time to the 1st defibrillation and the interval between defibrillations were longer in the mechanical CPR group without impacting the overall outcome. The number of defibrillations required to achieve ROSC or adrenalin doses did not differ between the groups.

Aim of the study We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals. Methods Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35mmHg, and were subjected to 2min of untreated CA followed by 8min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3mlkg −1 hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5mgkg −1 over 20min, followed by 1.5mgkg −1 infusion over 40min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed. Results There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes. Conclusions After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex.

The LUCAS™ device has been shown to improve organ perfusion during cardiac arrest in experimental studies. In this pilot study the aim was to compare short-term survival between cardiopulmonary resuscitation (CPR) performed with mechanical chest compressions using the LUCAS™ device and CPR performed with manual chest compressions. The intention was to use the results for power calculation in a larger randomised multicentre trial.In a prospective pilot study, from February 1, 2005, to April 1, 2007, 149 patients with out-of hospital cardiac arrest in two Swedish cities were randomised to mechanical chest compressions or standard CPR with manual chest compressions.After exclusion, the LUCAS and the manual groups contained 75 and 73 patients, respectively. In the LUCAS and manual groups, spontaneous circulation with a palpable pulse returned in 30 and 23 patients (p = 0.30), spontaneous circulation with blood pressure above 80/50 mm Hg remained for at least 5 min in 23 and 19 patients (p = 0.59), the number of patients hospitalised alive4h were 18 and 15 (p = 0.69), and the number discharged, alive 6 and 7 (p = 0.78), respectively.In this pilot study of out-of-hospital cardiac arrest patients we found no difference in early survival between CPR performed with mechanical chest compression with the LUCAS™ device and CPR with manual chest compressions. Data have been used for power calculation in a forthcoming multicentre trial.

Objective Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations. Data sources Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies. Study selection Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis. Conclusions and recommendations 1) The jury opines that the term "targeted temperature management" replace "therapeutic hypothermia." 2) The jury opines that descriptors (e.g., "mild") be replaced with explicit targeted temperature management profiles. 3) The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome. 4) The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32°C-34°C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence). 5) The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33°C-35.5°C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

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 26h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108h 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 24h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96h 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 24h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.

Background Laparoscopic liver surgery is evolving rapidly. Carbon dioxide embolism is a potential complication. The aim of this work was to study the frequency and severity of gas embolism (GE) during laparoscopic liver lobe resection in a pig model and the resulting cardiovascular and respiratory changes. Methods Fifteen anaesthetized piglets underwent laparoscopic left liver lobe resection. Haemodynamic and respiratory variables were monitored, including systemic and pulmonary arterial pressures, end-tidal CO2, and pulmonary dead space. Online blood gas monitoring and a transoesophageal echocardiography (TOE) were used. GE was graded semi-quantitatively as grade 0 (none), grade 1 (minor), or grade 2 (major), depending on the TOE results. Results In 10 of 15 piglets, GE occurred. In total, 33 separate episodes of GE were recorded. All 13 episodes of grade 2 and three of grade 1 were serious enough to cause mainly respiratory, but also haemodynamic effects. Mostly, grade 1 GE caused only minor respiratory or haemodynamic changes. Most variables were affected during grade 2 GE; the most important were Pa o 2, Pa co 2, end-tidal CO2, Vd/Vt, and mean pulmonary arterial pressure. Conclusions GE occurred frequently during laparoscopic liver resection in this experimental study. Approximately half of the embolisms were serious enough to cause respiratory or haemodynamic disturbances or both. Pending further human studies, a combination of several monitoring techniques, with narrow limits for the alarm settings, will ensure correct interpretation of the complex physiological response to GE and reveal it early enough to alert the anaesthetist and the surgeon to the ongoing problem.

Aim To study haemodynamic effects and changes in intravascular volume during hypothermia treatment, induced by ice-cold fluids and maintained by ice-packs followed by rewarming in patients after resuscitation from cardiac arrest. Materials and methods In 24 patients following successful restoration of spontaneous circulation (ROSC), hypothermia was induced with infusion of 4 °C normal saline and maintained with ice-packs for 26 h after ROSC. This was followed by passive rewarming. Transthoracic echocardiography was performed at 12, 24 and 48 h after ROSC to evaluate ejection fraction and intravascular volume status. Central venous pressure (CVP), central venous oxygen saturation (ScvO 2 ) and serum lactate were measured. Fluid balance was calculated. Results Twelve hours after ROSC, two separate raters independently estimated that 10 and 13 out of 23 patients had a decreased intravascular volume using transthoracic echocardiography. After 24 and 48 h this number had increased further to 14 and 13 out of 19 patients and 13 and 12 out of 21 patients. Calculated fluid balance was positive (4000 ml the day 1 and 2500 ml day 2). There was no difference in ejection fraction between the recording time points. Serum lactate and ScvO 2 were in the normal range when echocardiography exams were performed. CVP did not alter over time. Conclusions Our results support the hypothesis that inducing hypothermia following cardiac arrest, using cold intravenous fluid infusion does not cause serious haemodynamic side effects. Serial transthoracic echocardiographic estimation of intravascular volume suggests that many patients are hypovolaemic during therapeutic hypothermia and rewarming in spite of a positive fluid balance.

Aim To assess the regional vulnerability to ischemic damage and perfusion/metabolism mismatch of reperfused brain following restoration of spontaneous circulation (ROSC) after cardiac arrest. Method We used positron emission tomography (PET) to map cerebral metabolic rate of oxygen (CMRO 2 ), cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in brain of young pigs at intervals after resuscitation from cardiac arrest. After obtaining baseline PET recordings, ventricular fibrillation of 10min duration was induced, followed by mechanical closed-chest cardiopulmonary resuscitation (CPR) in conjunction with i.v. administration of 0.4U/kg of vasopressin. After CPR, external defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). CBF and CMRO 2 were mapped and voxelwise maps of OEF were calculated at times of 60, 180, and 300min after ROSC. Results There was hypoperfusion throughout the telencephalon at 60min, with a return towards baseline values at 300min. In contrast, there was progressively increasing CBF in cerebellum throughout the observation period. The magnitude of CMRO 2 decreased globally after ROSC, especially in cerebral cortex. The magnitude of OEF in cerebral cortex was 60% at baseline, tended to increase at 60min after ROSC, and declined to 50% thereafter, thus suggesting transition to an ischemic state. Conclusion The cortical regions tended most vulnerable to the ischemic insult with an oligaemic pattern and a low CMRO 2 whereas the cerebellum instead showed a pattern of luxury perfusion.

Aim This was an experimental study performed to investigate cerebral metabolism during hypothermia treatment and rewarming after resuscitation from cardiac arrest (CA). Materials and methods Sixteen pigs underwent CA followed by cardiopulmonary resuscitation (CPR). After randomisation into one hypothermic ( n =8) and one normothermic group ( n =8) the animals received infusion of 4 or 38°C saline, respectively. Following restoration of spontaneous circulation (ROSC) both groups were observed for 360min. The hypothermic group was cooled for 180min and then rewarmed. Temperature was not modulated in the normothermic group. Cerebral microdialysis was conducted and lactate/pyruvate (L/P)-ratio and glutamate were analysed. Intracranial pressure probe was inserted. Oxygen saturation in venous jugular bulb blood (SjO 2 ) was analysed. Results All animals initially had increased L/P-ratio (>30). A total of nine animals developed secondary increase. In the hypothermic group this was observed in 2/7 animals and in the normothermic group in 7/8 ( p =0.04). Glutamate increased initially in all animals with secondary increases in two animals in each group. No differences in L/P-ratio or glutamate were detected during the rewarming phase compared to the hypothermic phase. The hypothermic group had higher SjO 2 ( p =0.04). In both groups intracranial pressure increased after ROSC. Conclusion After resuscitation from CA there was a risk of cerebral secondary energy failure (reflected as an increased L/P-ratio) but hypothermia treatment seemed to counteract this effect. Cerebral oxygen extraction, measured by SjO 2, was increased in the hypothermic group probably due to reduced metabolism. Rewarming did not reveal any obvious harmful events.

Hypothermia treatment with cooling to a body temperature of 32-34°C has been shown to be an effective way of improving neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest (CA). The method is used clinically but there are still many questions on the biological mechanisms and on how the treatment is best performed. This thesis focuses on cerebral and haemodynamic effects of hypothermia and rewarming. A porcine model of CA was used. To shorten time to reach target temperature, induction of hypothermia, by means of infusion of 4°C cold fluid, was started already during ongoing cardiopulmonary resuscitation. The temperature was satisfactorily reduced without obvious haemodynamic disturbances. Cerebral effects of hypothermia and rewarming were studied. Microdialysis monitoring showed signs of cerebral energy failure (increased lactate/pyruvate-ratio) and excitotoxicity (increased glutamate) immediately after CA. There was a risk of secondary energy failure that was reduced by hypothermia. Intracranial pressure (ICP) increased gradually after CA irrespectively of if hypothermia was used or not. There were no indications of increasing cerebral disturbances during rewarming. Haemodynamic effects of hypothermia treatment and rewarming were examined in a study of patients successfully resuscitated after CA. Hypothermia was induced by means of cold intravenous infusion. No negative effects on the cardiovascular system were revealed. There were indications of decreased intravascular volume in spite of a positive fluid balance. Cerebral microdialysis and ICP recording were performed in four patients. All patients had signs of energy failure and excitotoxicity following CA. ICP was only exceptionally above 20 mmHg. In contrast to the experimental study indications of increasing ischemia were seen during rewarming. Glycerol had a biphasic pattern, perhaps due to an overspill of metabolites from the general circulation. As most patients become extensively anti-coagulated following CA, intracranial monitoring is not suitable to be used in routine care.

Background: Special clinical situations where general hypothermia cannot be recommended but can be a useful treatment demand a new approach, selective brain cooling. The purpose of this study was to selectively cool the brain with cold saline circulating in balloon catheters introduced into the nasal cavity in pigs. Material and methods: Twelve anaesthetised pigs were subjected to selective cerebral cooling for a period of 6 h. Cerebral temperature was towered by means of bilaterally introduced nasal balloon catheters perfused with saline cooled by a heat exchanger to 8-10 degrees C. Brain temperature was measured in both cerebral hemispheres. Body temperature was measured in rectum, oesophagus and the right atrium. The pigs were normoventilated and haemodynamic variables were measured continuously. Acid-base and electrolyte status was measured hourly. Results: Cerebral hypothermia was induced rapidly and within the first 20 min of cooling cerebral temperature was lowered from 38.1 +/- 0.6 degrees C by a mean of 2.8 +/- 0.6 to 35.3 +/- 0.6 degrees C. Cooling was maintained for 6 h and the final brain temperature was 34.7 +/- 0.9 degrees C. Concomitantly, the body temperature, as reflected by oesophageal temperature was decreased from 38.3 +/- 0. 5 to 36.6 +/- 0.9 degrees C. No circulatory or metabolic disturbances were noted. Conclusions: Inducing selective brain hypothermia with cold saline via nasal balloon catheters can effectively be accomplished in pigs, with no major disturbances in systemic circulation or physiological variables. The temperature gradients between brain and body can be maintained for at least 6 h. (Less)

Bleeding is a known and CO2 embolization a suggested risk factor for increased morbidity after laparoscopic liver resection. Devices for laparoscopic liver parenchymal transection must be evaluated for safety in this context. Twelve piglets underwent laparoscopic surgery during CO2 pneumoperitoneum, each animal receiving three 6 cm long transections into the liver parenchyma made with ultrasonic dissector, ultrasonic shears and vessel sealing system, respectively. Endpoints were bleeding, operation time and gas embolization. The transections and embolization events, evaluated with transesophageal echocardiography, were video recorded. Bleeding and embolization were also assessed on video tapes and operating time measured. Arterial blood gases were recorded on line. The ultrasonic dissector was least advantageous in terms of bleeding and operation time. Gas embolization was more frequent with the vessel sealing system than with the ultrasonic dissector and ultrasonic shears. During two episodes of gas embolization, pCO2 increased and pO2 and pH decreased. Use of all three devices is feasible. Bleeding and operation time are greatest with the ultrasonic dissector. Gas embolization occurs during transection, though in most instances it is completely harmless. Laparoscopic liver surgery with these techniques used may pose a risk of gas embolization with clinical implications. Monitoring for such events is probably to be recommended.

Automatic mechanical chest compressions during cardiopulmonary resuscitation : What is the evidence for its use?

Objective To perform two predefined sub-group analyses within the LINC study and evaluate if the results were supportive of the previous reported intention to treat (ITT) analysis. Methods Predefined subgroup analyses from the previously published LINC study were performed. The Per-Protocol population (PPP) included the randomized patients included in the ITT-population but excluding those with violated inclusion or exclusion criteria and those that did not get the actual treatment to which the patient was randomized. In the Pre-Defined population (PDP) analyses patients were also excluded if the dispatch time to ambulance arrival at the address exceeded 12min, there was a non-witnessed cardiac arrest, or if it was not possible to determine whether the arrest was witnessed or not, and those cases where LUCAS was not brought to the scene at the first instance. Results After exclusion from the 2589 patients within the ITT-population, the Per-Protocol analysis was performed in 2370 patients and the Pre-Defined analysis within 1133 patients. There was no significant difference in 4-h survival of patients between the mechanical-CPR group and the manual-CPR group in the Per-Protocol population; 279 of 1172 patients (23.8%) versus 281 of 1198 patients (23.5%) (risk difference −0.35%, 95% C.I. −3.1 to 3.8, p =0.85) or in the Pre-Defined population; 176 of 567 patients (31.0%) versus 192 of 566 patients (33.9%) (risk difference −2.88%, 95% C.I. −8.3 to 2.6, p =0.31). There was no difference in any of the second outcome variables analyzed in the Pre-Protocol or Pre-Defined populations. Conclusions The results from these predefined sub-group analyses of the LINC study population did not show any difference in 4h survival or in secondary outcome variables between patients treated with mechanical-CPR or manual-CPR. This is consistent with the previously published ITT analysis.

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC).In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow.Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC.Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC.By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor.

To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury.Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation.There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P0.01).In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.

To determine whether activation of coagulation and inflammation during cardiac arrest results in a reduction of antithrombin (AT) and an increase in thrombin-antithrombin (TAT) complex during reperfusion.Ventricular fibrillation (VF) was induced in ten anaesthetized pigs. After a 5-min non-intervention interval, closed-chest cardiopulmonary resuscitation (CPR) was performed for 9 min before defibrillation was attempted. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h and repeated blood samples were taken for assay of AT, TAT and eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)).AT began to decrease 15 min after ROSC and the reduction continued throughout the observation period (P0.05). The lowest mean value (79%) occurred 60 min after ROSC. The TAT level was increased during the first 3 h after ROSC (P0.05), indicating thrombin generation. The eicosanoids were increased throughout the observation period (P0.05).AT is reduced and TAT and eicosanoids are increased after cardiac arrest, indicating activation of coagulation and inflammation.

BACKGROUND: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest.METHODS: Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF(2 alpha)), inflammation (15-keto-dihydro-PGF(2 alpha)), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR.RESULTS: Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5-15 min after ROSC. Jugular venous 8-iso-PGF(2 alpha) and hypoxanthine after ROSC were correlated to 24 h neurological outcomeCONCLUSIONS: A combination of cerebral blood flow promoting measures and administration of alpha-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase.

Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population.We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥ 18 years of age with a GCS8 at hospital admission and treated with TTM at 32-34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome.416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p0.001) and less sepsis (1.2 vs. 5.7%, p0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p0.001) and a similar incidence of good functional outcome.Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome.

Aim The reported incidence of injuries due to cardiopulmonary resuscitation using manual chest compressions (manual CPR) varies greatly. Our aim was to elucidate the incidence of CPR-related injuries by manual chest compressions compared to mechanical chest compressions with the LUCAS device (mechanical CPR) in non-survivors after out-of-hospital cardiac arrest. Methods In this prospective multicentre trial, including 222 patients (83 manual CPR/139 mechanical CPR), autopsies were conducted after unsuccessful CPR and the results were evaluated according to a specified protocol. Results Among the patients included, 75.9% in the manual CPR group and 91.4% in the mechanical CPR group (p = 0.002) displayed CPR-related injuries. Sternal fractures were present in 54.2% of the patients in the manual CPR group and in 58.3% in the mechanical CPR group (p = 0.56). Of the patients in the manual CPR group, there were 64.6% with at least one rib fracture versus 78.8% in the mechanical CPR group (p = 0.02). The median number of rib fractures among patients with rib fractures was 7 in the manual CPR group and 6 in the mechanical CPR group. No CPR-related injury was considered to be the cause of death. Conclusion In patients with unsuccessful CPR after out-of-hospital cardiac arrest, rib fractures were more frequent after mechanical CPR but there was no difference in the incidence of sternal fractures. No injury was deemed fatal by the pathologist.

Background Positive pressure mechanical ventilation causes rhythmic changes in thoracic pressure and central blood flow. If entrainment occurs, it could be easier for carbon dioxide to enter through a wounded vein during laparoscopic liver lobe resection (LLR). High-frequency jet ventilation (HFJV) is a ventilating method that does not cause pronounced pressure or blood flow changes. This study aimed to investigate whether HFJV could influence the frequency, severity, or duration of gas embolism (GE) during LLR. Methods Twenty-four anaesthetized piglets underwent lobe resection and were randomly assigned to either normal frequency ventilation (NFV) or HFJV (n=12 per group). During resection, a standardized injury to the left hepatic vein was created to increase the risk of GE. Haemodynamic and respiratory variables were monitored. Online blood gas monitoring and transoesophageal echocardiography were used. GE occurrence and severity were graded as 0 (none), 1 (minor), or 2 (major), depending on the echocardiography results. Results GE duration was shorter in the HFJV group (P=0.008). However, no differences were found between the two groups in the frequency or severity of embolism. Incidence of Grade 2 embolism was less than that found in previous studies and physiological responses to embolism were variable. Conclusion HFJV shortened the mean duration of GE during LLR and was a feasible ventilation method during the procedure. Individual physiological responses to GE were unpredictable.

To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.Randomized controlled study.University hospital research laboratory.A total of 20 male anesthetized piglets.Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.

Intra-aortic balloon occlusion during experimental cardiopulmonary resuscitation (CPR) improves coronary perfusion pressure and resuscitability and provides unique access to the central circulation. It has been hypothesized that administration of epinephrine into the aortic arch in combination with aortic occlusion would further improve haemodynamics during CPR, resuscitability and 24 h survival. In 16 anaesthetised dogs intravascular catheters were placed for hemodynamic and blood gas monitoring. An aortic balloon catheter was placed by femoral artery insertion with its tip just distal to the left subclavian artery. Ventricular fibrillation for 7.5 min without CPR, 2.5 min of Basic Life Support with chest compressions and ventilation with 100% oxygen were followed by 30 min of Advanced Cardiac Life Support (ACLS) with systemic canine drug dosages. The intra-aortic balloon was inflated when ACLS started and gradually deflated shortly after restoration of spontaneous circulation (ROSC). Epinephrine, in 100 microg/kg boluses every 5 min until the heart was restarted or 30 min had elapsed was administered through the intra-aortic catheter in the experimental group (n = 8) and via a central venous catheter in the control group (n = 8). Coronary perfusion pressure increased during the ACLS period in both groups (P < 0.05) with no difference between the groups and there was no difference in the frequency of ROSC (experimental group 5/8, control group 4/8). Furthermore with respect to 24 h survival, there was no difference between the experimental group (2/8) and the control group (3/8). Severe macroscopic haemorrhagic necrosis of the myocardium in the dogs with ROSC was found in 4/5 in the experimental group compared to 1/4 in the control group. In conclusion, intra-aortic administration of 100 microg/kg epinephrine doses combined with aortic occlusion during experimental CPR did not alter outcome.

Importance A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials. Objective To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions (mechanical CPR), compared with manual cardiopulmonary resuscitation (manual CPR), according to guidelines, would improve 4-hour survival. Design, setting, and participants Multicenter randomized clinical trial of 2589 patients with out-of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. Interventions Patients were randomized to receive either mechanical chest compressions (LUCAS Chest Compression System, Physio-Control/Jolife AB) combined with defibrillation during ongoing compressions (n = 1300) or to manual CPR according to guidelines (n = 1289). Main outcomes and measures Four-hour survival, with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category (CPC) score. A CPC score of 1 or 2 was classified as a good outcome. Results Four-hour survival was achieved in 307 patients (23.6%) with mechanical CPR and 305 (23.7%) with manual CPR (risk difference, -0.05%; 95% CI, -3.3% to 3.2%; P > .99). Survival with a CPC score of 1 or 2 occurred in 98 (7.5%) vs 82 (6.4%) (risk difference, 1.18%; 95% CI, -0.78% to 3.1%) at intensive care unit discharge, in 108 (8.3%) vs 100 (7.8%) (risk difference, 0.55%; 95% CI, -1.5% to 2.6%) at hospital discharge, in 105 (8.1%) vs 94 (7.3%) (risk difference, 0.78%; 95% CI, -1.3% to 2.8%) at 1 month, and in 110 (8.5%) vs 98 (7.6%) (risk difference, 0.86%; 95% CI, -1.2% to 3.0%) at 6 months with mechanical CPR and manual CPR, respectively. Among patients surviving at 6 months, 99% in the mechanical CPR group and 94% in the manual CPR group had CPC scores of 1 or 2. Conclusions and relevance Among adults with out-of-hospital cardiac arrest, there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline-adherent manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. In clinical practice, mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR. Trial registration clinicaltrials.gov Identifier: NCT00609778.

To evaluate the blood flow and perfusion pressure differences observed during open- vs. closed-chest cardiopulmonary resuscitation (CPR), including the effects of epinephrine and sodium bicarbonate administration.Prospective, randomized, controlled trial.Experimental animal laboratory in a university hospital.A total of 35 anesthetized piglets.After tracheostomy and insertion of arterial, right atrial, and pulmonary arterial catheters, thoracotomy was performed with placement of a pulmonary arterial flow probe and left atrial catheter. Ventricular fibrillation was induced and followed by 15 mins of either open-chest (n = 14) or closed-chest (n = 21) CPR. A 4-min infusion of 50 mmol of sodium bicarbonate or saline was added at the start of CPR. After 8 mins of CPR, 0.5 mg of epinephrine was given intravenously, and after 15 mins, direct current (DC) shocks were used to revert the heart to sinus rhythm.Blood flow was studied using transit-time ultrasound flowmetry. In an extended group, intrathoracic pressure was measured for calculation of transmural pressure. Before epinephrine administration, mean pulmonary arterial flow (cardiac output) was reduced: a) during closed-chest CPR relatively more than pulmonary perfusion pressure but in proportion to systemic perfusion pressure; b) during open-chest CPR relatively less than pulmonary perfusion pressure but still in proportion to systemic perfusion pressure. Epinephrine administration temporarily increased systemic perfusion pressure during both closed- and open-chest CPR but temporarily decreased pulmonary perfusion pressure only during closed-chest CPR. After epinephrine administration, cardiac output temporarily decreased during both closed-and open-chest CPR.Open-chest CPR resulted in better cardiac output and systemic perfusion pressure than closed-chest CPR. However, cardiac output values obtained with both methods were much lower than previously reported. After epinephrine administration, cardiac output became extremely low with both methods.

Background The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. Methods Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Results Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1–2) in nine patients. Conclusions Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.

Only approximately 10% of patients encountering a cardiac arrest (CA) and subsequent cardiopulmonary resuscitation survive to a meaningful life. One of the most important causes for this low survival rate is the ischemia-reperfusion injury that hits the brain. This review summarizes some of the more important mechanisms causing cerebral injury. Thus, we describe some of our findings when performing genome-wide transcriptional profiling as well as histological and immunohistological staining of cerebral cortical areas. In order to shed some light on therapeutic opportunities, our findings relating to the use of induced mild hypothermia and methylene blue as neuroprotective agents are reviewed. Furthermore, we would like to share some interesting data on gender differences and effects of estrogen on the ensuing cerebral injury occurring after hypovolemic CA.

Various techniques are used to transect the liver. With increase in laparoscopic liver resections (LLR), it is of even more interest to develop surgical techniques to minimize bleeding and the risk for gas embolism during transection. Instrument like argon enhanced coagulator provides good hemostasis but increases the danger of gas embolism. The CO2 pneumoperitoneum that is routinely used in most types of laparoscopic surgery can be modified by the use of different gas pressure. It can be assumed that different pressure influences bleeding but also the risk for gas embolism.In presented porcine studies, three instrumental combinations have been studied. In study I sixteen piglets were randomized to LLR with either the cavitron ultrasonic aspirator (CUSA™) in combination with vessels sealing system (Ligasure™) or with CUSA™ and ultrascision scissors (Autosonix™), with the endpoints of intra-operative bleeding and gas embolism. In study IV sixteen piglets were randomized to LLR either with staple device (Endo-GIA™) or the Ligasure™ - CUSA™ combination with same primary endpoints and additionally secondary endpoints of effect on gas-exchange, systemic- and pulmonary hemodynamic.Focusing on intra-abdominal pressure (IAP) in study II, sixteen piglets were randomized to LLR with an IAP of either 8 or 16 mmHg. Primary endpoints were bleeding and gas embolism and secondary endpoints, effect on gas-exchange, systemic- and pulmonary hemodynamic.In study III effect of argon gas was tested during LLR. Sixteen piglets were randomized to either argon pneumoperitoneum or CO2 pneumoperitoneum. Primary endpoints were effect on gas-exchange, systemic- and pulmonary hemodynamic.In presented studies, we tested efficacy and safety of different techniques for LLR. CUSA™ can be used in combination with either Ligasure™ or Autosonix™. However, Ligasure™ reduces the amount of bleeding. The recent introduction of staplers seems promising with a further reduction in bleeding, gas embolism, and operating time. The IAP influences both the amount of bleeding as well as gas embolism. It seems reasonable to use a higher IAP to decrease bleeding with caution and with close monitoring for gas embolism. Argon gas embolism gives more extensive effect on gas-exchange and hemodynamic and should probably be avoided in this type of surgery.

Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.

Background Intranasal balloon catheters circulated with cold saline have previously been used for the induction and maintenance of selective brain cooling in pigs with normal circulation. In the present study, we investigated the feasibility of therapeutic hypothermia initiation, maintenance and rewarming using such intranasal balloon catheters with or without addition of intravenous ice-cold fluids during and after cardiac arrest treatment in pigs. Material and methods Cardiac arrest was induced in 20 anaesthetised pigs. Following 8 min of cardiac arrest and 1 min of cardiopulmonary resuscitation (CPR), cooling was initiated after randomisation with either intranasal cooling (N) or combined with intravenous ice-cold fluids (N+S). Hypothermia was maintained for 180 min, followed by 180 min of rewarming. Brain and oesophageal temperatures, haemodynamic variables and intracranial pressure (ICP) were recorded. Results Brain temperatures reductions after cooling did not differ (3.8 +/- 0.7 degrees C in the N group and 4.3 +/- 1.5 degrees C in the N+S group; P=0.47). The corresponding body temperature reductions were 3.6 +/- 1.2 degrees C and 4.6 +/- 1.5 degrees C (P=0.1). The resuscitation outcome was similar in both groups. Mixed venous oxygen saturation was lower in the N group after cooling and rewarming (P=0.024 and 0.002, respectively) as compared with the N+S group. ICP was higher after rewarming in the N group (25.2 +/- 2.9 mmHg; P=0.01) than in the N+S group (15.7 +/- 3.3 mmHg). Conclusions Intranasal balloon catheters can be used for therapeutic hypothermia initiation, maintenance and rewarming during CPR and after successful resuscitation in pigs. (Less)

Therapeutic hypothermia (TH) after cardiac arrest protects from neurological sequels and death and is recommended in guidelines. The Hypothermia Registry was founded to the monitor outcome, performance and complications of TH.Data on out-of-hospital cardiac arrest (OHCA) patients admitted to intensive care for TH were registered. Hospital survival and long-term outcome (6-12 months) were documented using the Cerebral Performance Category (CPC) scale, CPC 1-2 representing a good outcome and 3-5 a bad outcome.From October 2004 to October 2008, 986 TH-treated OHCA patients of all causes were included in the registry. Long-term outcome was reported in 975 patients. The median time from arrest to initiation of TH was 90 min (interquartile range, 60-165 min) and time to achieving the target temperature (or =34 degrees C) was 260 min (178-400 min). Half of the patients underwent coronary angiography and one-third underwent percutaneous coronary intervention (PCI). Higher age, longer time to return of spontaneous circulation, lower Glasgow Coma Scale at admission, unwitnessed arrest and initial rhythm asystole were all predictors of bad outcome, whereas time to initiation of TH and time to reach the goal temperature had no significant association. Bleeding requiring transfusion occurred in 4% of patients, with a significantly higher risk if angiography/PCI was performed (2.8% vs. 6.2%P=0.02).Half of the patients survived, with90% having a good neurological function at long-term follow-up. Factors related to the timing of TH had no apparent association to outcome. The incidence of adverse events was acceptable but the risk of bleeding was increased if angiography/PCI was performed.

Cerebral blood flow (CBF) during cardiopulmonary resuscitation and after restoration of spontaneous circulation (ROSC) from cardiac arrest has previously been measured with the microspheres and laser Doppler techniques. We used positron emission tomography (PET) with [15O]--water to map the haemodynamic changes after ROSC in nine young pigs. After the baseline PET recording, ventricular fibrillation of 5 min duration was induced, followed by closed-chest cardiopulmonary resuscitation (CPR) in conjunction with IV administration of three bolus doses of adrenaline (epinephrine). After CPR, external defibrillatory shocks were applied to achieve ROSC. CBF was measured at intervals during 4h after ROSC. Relative to the mean global CBF at baseline (32+/-5 ml hg(-1)min(-1)), there was a substantial global increase in CBF at 10 min, especially in the diencephalon. This was followed by an interval of cortical hypoperfusion and a subsequent gradual return to baseline values.

Laparoscopic liver surgery is complicated due to the structure of this organ with open sinusoids. A serious disadvantage is the risk of gas embolism (GE) due to CO2 pneumoperitoneum. CO2 can enter the vascular system through a wounded vein. A common opinion is that gas fluxes along a pressure gradient, e.g. CVP-intra abdominal pressure (IAP). The occurrence of GE could also be eased by entrainment, a ‘Venturi-like’ effect, due to cyclic differences in thoracic pressure and blood flow caused by mechanical ventilation at normal frequency.The aims of these studies were to survey, in a porcine model, the influence on respiratory and haemodynamic variables by GE, to determine at what frequency, severity and duration GE occurs during laparoscopic liver resection (LLR) and whether there are methods to influence the occurrence or severity of GE.Pulmonary and circulatory variables were monitored and measured as well as continuous blood gas monitoring. Transoesophageal echocardiogram was used to identify GE and, according to the amount of bubbles in the right outflow tract of the heart, GE was graded as 0, 1 and 2. Pneumoperitoneum was created by using CO2and IAP was set to 16 mm Hg.A single bolus dose of CO2 influenced respiratory and haemodynamic variables for at least 4 h. During LLR GE occurred in 65-70% of the animals, of which the more serious caused negative influence on cardiopulmonary variables.Elevated PEEP (15 cm H2O) increased CVP but GE occurred irrespective if CVP was lower than or exceeded IAP. In two last studies, a hepatic vein was cut and left open for 3 m before it was clipped. Interestingly, no signs of GE were seen despite an open vein and IAP > CVP in 8 of 20 animals. In the last study high frequency jet ventilation was used in order to minimise the risk of entrainment. The duration of GE was shortened.The occurrence of GE seemed to be influenced by several different factors. The physiological reaction of a GE is impossible to predict for a specific patient, and depends among other factors on comorbidity, and amount, site and entrance rate of GE.