Oxygenation and ventilation during prolonged experimental cardiopulmonary resuscitation with either continuous or 30:2 compression-to-ventilation ratios together with 10 cmH20 positive end-expiratory pressure.

BACKGROUND: In refractory out-of-hospital cardiac arrest, the patient is commonly transported to hospital with mechanical continuous chest compressions (CCC). Limited data are available on the optimal ventilation strategy. Accordingly, we compared arterial oxygenation and haemodynamics during manual asynchronous continuous ventilation and compressions with a 30:2 compression-to-ventilation ratio together with the use of 10 cmH2O positive end-expiratory pressure (PEEP). METHODS: Intubated and anaesthetized landrace pigs with electrically induced ventricular fibrillation were left untreated for 5 min (n = 31, weight ca. 55 kg), after which they were randomized to either the CCC group or the 30:2 group with the the LUCAS® 2 piston device and bag-valve ventilation with 100% oxygen targeting a tidal volume of 8 ml/kg with a PEEP of 10 cmH2O for 35 min. Arterial blood samples were analysed every 5 min, vital signs, near-infrared spectroscopy and electrical impedance tomography (EIT) were measured continuously, and post-mortem CT scans of the lungs were obtained. RESULTS: The arterial blood values (median + interquartile range) at the 30-min time point were as follows: PaO2: 180 (86-302) mmHg for the 30:2 group; 70 (49-358) mmHg for the CCC group; PaCO2: 41 (29-53) mmHg for the 30:2 group; 44 (21-67) mmHg for the CCC group; and lactate: 12.8 (10.4-15.5) mmol/l for the 30:2 group; 14.7 (11.8-16.1) mmol/l for the CCC group. The differences were not statistically significant. In linear mixed models, there were no significant differences between the groups. The mean arterial pressures from the femoral artery, end-tidal CO2, distributions of ventilation from EIT and mean aeration of lung tissue in post-mortem CTs were similar between the groups. Eight pneumothoraces occurred in the CCC group and 2 in the 30:2 group, a statistically significant difference (p = 0.04). CONCLUSIONS: The 30:2 and CCC protocols with a PEEP of 10 cmH2O resulted in similar gas exchange and vital sign outcomes in an experimental model of prolonged cardiac arrest with mechanical compressions, but the CCC protocol resulted in more post-mortem pneumothoraces.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis.

Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. Funding: None.

Development and internal validation of an algorithm for estimating mortality in patients encountered by physician-staffed helicopter emergency medical services.

BACKGROUND: Severity of illness scoring systems are used in intensive care units to enable the calculation of adjusted outcomes for audit and benchmarking purposes. Similar tools are lacking for pre-hospital emergency medicine. Therefore, using a national helicopter emergency medical services database, we developed and internally validated a mortality prediction algorithm. METHODS: We conducted a multicentre retrospective observational register-based cohort study based on the patients treated by five physician-staffed Finnish helicopter emergency medical service units between 2012 and 2019. Only patients aged 16 and over treated by physician-staffed units were included. We analysed the relationship between 30-day mortality and physiological, patient-related and circumstantial variables. The data were imputed using multiple imputations employing chained equations. We used multivariate logistic regression to estimate the variable effects and performed derivation of multiple multivariable models with different combinations of variables. The models were combined into an algorithm to allow a risk estimation tool that accounts for missing variables. Internal validation was assessed by calculating the optimism of each performance estimate using the von Hippel method with four imputed sets. RESULTS: After exclusions, 30 186 patients were included in the analysis. 8611 (29%) patients died within the first 30 days after the incident. Eleven predictor variables (systolic blood pressure, heart rate, oxygen saturation, Glasgow Coma Scale, sex, age, emergency medical services vehicle type [helicopter vs ground unit], whether the mission was located in a medical facility or nursing home, cardiac rhythm [asystole, pulseless electrical activity, ventricular fibrillation, ventricular tachycardia vs others], time from emergency call to physician arrival and patient category) were included. Adjusted for optimism after internal validation, the algorithm had an area under the receiver operating characteristic curve of 0.921 (95% CI 0.918 to 0.924), Brier score of 0.097, calibration intercept of 0.000 (95% CI -0.040 to 0.040) and slope of 1.000 (95% CI 0.977 to 1.023). CONCLUSIONS: Based on 11 demographic, mission-specific, and physiologic variables, we developed and internally validated a novel severity of illness algorithm for use with patients encountered by physician-staffed helicopter emergency medical services, which may help in future quality improvement.

Factors associated with fever after cardiac arrest: A post-hoc analysis of the FINNRESUSCI study.

BACKGROUND: Fever after cardiac arrest may impact outcome. We aimed to assess the incidence of fever in post-cardiac arrest patients, factors predicting fever and its association with functional outcome in patients treated without targeted temperature management (TTM). METHODS: The FINNRESUSCI observational cohort study in 2010-2011 included intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients from all five Finnish university hospitals and 14 of 15 central hospitals. This post hoc analysis included those FINNRESUSCI study patients who were not treated with TH. We defined fever as at least one temperature measurement of ≥37.8°C within 72 h of ICU admission. The primary outcome was favourable functional outcome at 12 months, defined as cerebral performance category (CPC) of 1 or 2. Binary logistic regression models including witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm and delay of return of spontaneous circulation were used to compare the functional outcomes of the groups. RESULTS: There were 67,428 temperature measurements from 192 patients, of whom 89 (46%) experienced fever. Twelve-month CPC was missing in 7 patients, and 51 (28%) patients had favourable functional outcome at 12 months. The patients with shockable initial rhythms had a lower incidence of fever within 72 h of ICU admission (28% vs. 72%, p < .01), and the patients who experienced fever had a longer median return of spontaneous circulation (ROSC) delay (20 [IQR 10-30] vs. 14 [IQR 9-22] min, p < .01). Only initial non-shockable rhythm (OR 2.99, 95% CI 1.51-5.94) was associated with increased risk of fever within the first 72 h of ICU admission. Neither time in minutes nor area (minutes × degree celsius over threshold) over 37°C, 37.5°C, 38°C, 38.5°C, 39°C, 39.5°C or 40°C were significantly different in those with favourable functional outcome compared to those with unfavourable functional outcome within the first 24, 48 or 72 h from ICU admission. Fever was not associated with favourable functional outcome at 12 months (OR 0.90, 95% CI 0.44-1.84). CONCLUSIONS: Half of OHCA patients not treated with TTM developed fever. We found no association between fever and outcome.

Mastering the brain in critical conditions: an update.

Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events-vascular damage in strokes and biomechanical damage in traumatic brain injuries-they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Trends in Incidence and Outcomes of Cardiac Arrest Occurring in Swedish ICUs.

OBJECTIVE: To determine temporal trends in the incidence of cardiac arrest occurring in the ICU (ICU-CA) and its associated long-term mortality. DESIGN: Retrospective observational study. SETTING: Swedish ICUs, between 2011 and 2017. PATIENTS: Adult patients (≥18 yr old) recorded in the Swedish Intensive Care Registry (SIR). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU-CA was defined as a first episode of cardiopulmonary resuscitation and/or defibrillation following an ICU admission, as recorded in SIR or the Swedish Cardiopulmonary Resuscitation Registry. Annual adjusted ICU-CA incidence trend (all admissions) was estimated using propensity score-weighted analysis. Six-month mortality trends (first admissions) were assessed using multivariable mixed-effects logistic regression. Analyses were adjusted for pre-admission characteristics (sex, age, socioeconomic status, comorbidities, medications, and healthcare utilization), illness severity on ICU admission, and admitting unit. We included 231,427 adult ICU admissions. Crude ICU-CA incidence was 16.1 per 1,000 admissions, with no significant annual trend in the propensity score-weighted analysis. Among 186,530 first admissions, crude 6-month mortality in ICU-CA patients was 74.7% (95% CI, 70.1-78.9) in 2011 and 68.8% (95% CI, 64.4-73.0) in 2017. When controlling for multiple potential confounders, the adjusted 6-month mortality odds of ICU-CA patients decreased by 6% per year (95% CI, 2-10). Patients admitted after out-of-hospital or in-hospital cardiac arrest had the highest ICU-CA incidence (136.1/1,000) and subsequent 6-month mortality (76.0% [95% CI, 73.6-78.4]). CONCLUSIONS: In our nationwide Swedish cohort, the adjusted incidence of ICU-CA remained unchanged between 2011 and 2017. More than two-thirds of patients with ICU-CA did not survive to 6 months following admission, but a slight improvement appears to have occurred over time.

Dysnatremia at ICU admission and functional outcome of cardiac arrest: insights from four randomised controlled trials.

PURPOSE: To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest. METHODS: We pooled data from four randomised clinical trials in post-cardiac-arrest patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135-145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP). RESULTS: We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 [15-29] minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 [24%] vs. 363/893 [41%]; P = 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26-0.79, p = 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis. CONCLUSIONS: Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating. Registration ClinicalTrial.gov, NCT01994772, November 2013, 21.

Postresuscitation management.

PURPOSE OF REVIEW: To describe the most recent scientific evidence on ventilation/oxygenation, circulation, temperature control, general intensive care, and prognostication after successful resuscitation from adult cardiac arrest. RECENT FINDINGS: Targeting a lower oxygen target (90-94%) is associated with adverse outcome. Targeting mild hypercapnia is not associated with improved functional outcomes or survival. There is no compelling evidence supporting improved outcomes associated with a higher mean arterial pressure target compared to a target of >65 mmHg. Noradrenalin seems to be the preferred vasopressor. A low cardiac index is common over the first 24 h but aggressive fluid loading and the use of inotropes are not associated with improved outcome. Several meta-analyses of randomized clinical trials show conflicting results whether hypothermia in the 32-34°C range as compared to normothermia or no temperature control improves functional outcome. The role of sedation is currently under evaluation. Observational studies suggest that the use of neuromuscular blockade may be associated with improved survival and functional outcome. Prophylactic antibiotic does not impact on outcome. No single predictor is entirely accurate to determine neurological prognosis. The presence of at least two predictors of severe neurological injury indicates that an unfavorable neurological outcome is very likely. SUMMARY: Postresuscitation care aims for normoxemia, normocapnia, and normotension. The optimal target core temperature remains a matter of debate, whether to implement temperature management within the 32-34°C range or focus on fever prevention, as recommended in the latest European Resuscitation Council/European Society of Intensive Care Medicine guidelines Prognostication of neurological outcome demands a multimodal approach.

Effect of antiplatelet and anticoagulant medication use on injury severity and mortality in patients with traumatic brain injury treated in the intensive care unit.

BACKGROUND: Antiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)-treated TBI patients with 1-year mortality and head CT findings. METHOD: We conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003-2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality. RESULTS: Of 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02-2.58) and anticoagulants (OR 1.43, 95% CI 1.06-1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16-4.22) and anticoagulants (1.50, 95% CI 0.97-2.32) were associated with an increased risk of 1-year mortality. CONCLUSIONS: Both antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU-treated TBI patients.

The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials.

BACKGROUND: We aimed to study the incidence of acute kidney injury (AKI) in out-of-hospital cardiac arrest (OHCA) patients treated according to low-normal or high-normal mean arterial pressure (MAP) targets. METHODS: A post hoc analysis of the COMACARE (NCT02698917) and Neuroprotect (NCT02541591) trials that randomized patients to lower or higher targets for the first 36 h of intensive care. Kidney function was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. We used Cox regression analysis to identify factors associated with AKI after OHCA. RESULTS: A total of 227 patients were included: 115 in the high-normal MAP group and 112 in the low-normal MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 in the high-normal MAP group and 46 in the low-normal MAP group (p = 0.51). The median creatinine and daily urine output were 85 µmol/l and 1730 mL/day in the high-normal MAP group and 87 µmol/l and 1560 mL/day in the low-normal MAP group. In a Cox regression model, independent AKI predictors were no bystander cardiopulmonary resuscitation (p < 0.01), non-shockable rhythm (p < 0.01), chronic hypertension (p = 0.03), and time to the return of spontaneous circulation (p < 0.01), whereas MAP target was not an independent predictor (p = 0.29). CONCLUSION: Any AKI occurred in four out of ten OHCA patients. We found no difference in the incidence of AKI between the patients treated with lower and those treated with higher MAP after CA. Higher age, non-shockable initial rhythm, and longer time to ROSC were associated with shorter time to AKI. CLINICAL TRIAL REGISTRATION: COMACARE (NCT02698917), NEUROPROTECT (NCT02541591).

Hospital-administered ECPR for out-of-hospital cardiac arrest: an observational cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a treatment method for refractory out-of-hospital cardiac arrest (OHCA) requiring a complex chain of care. METHODS: All cases of OHCA between 1 January 2016 and 31 December 2021 in the Helsinki University Hospital catchment area in which the ECPR protocol was activated were included in the study. The protocol involved patient transport from the emergency site with ongoing mechanical cardiopulmonary resuscitation (CPR) directly to the cardiac catheterisation laboratory where the implementation of extracorporeal membrane oxygenation (ECMO) was considered. Cases of hypothermic cardiac arrest were excluded. The main outcomes were the number of ECPR protocol activations, duration of prehospital and in-hospital time intervals, and whether the ECPR candidates were treated using ECMO or not. RESULTS: The prehospital ECPR protocol was activated in 73 cases of normothermic OHCA. The mean patient age (SD) was 54 (±11) years and 67 (91.8%) of them were male. The arrest was witnessed in 67 (91.8%) and initial rhythm was shockable in 61 (83.6%) cases. The median ambulance response time (IQR) was 9 (7-11) min. All patients received mechanical CPR, epinephrine and/or amiodarone. Seventy (95.9%) patients were endotracheally intubated. The median (IQR) highest prehospital end-tidal CO2 was 5.5 (4.0-6.9) kPa.A total of 37 (50.7%) patients were treated with venoarterial ECMO within a median (IQR) of 84 (71-105) min after the arrest. Thirteen (35.1%) of them survived to discharge and 11 (29.7%) with a cerebral performance category (CPC) 1-2. In those ECPR candidates who did not receive ECMO, 8 (22.2%) received permanent return of spontaneuous circulation during transport or immediately after hospital arrival and 6 (16.7%) survived to discharge with a CPC 1-2. CONCLUSIONS: Half of the ECPR protocol activations did not lead to ECMO treatment. However, every fourth ECPR candidate and every third patient who received ECMO-facilitated resuscitation at the hospital survived with a good neurological outcome.

The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury.

PURPOSE: Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown. METHODS: We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010-2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5-8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI. RESULTS: Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47-1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI [Formula: see text] 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2-22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome. CONCLUSION: EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.