Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

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.

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.

Indoleamine 2,3-Dioxygenase Deletion to Modulate Kynurenine Pathway and to Prevent Brain Injury after Cardiac Arrest in Mice.

BACKGROUND: The catabolism of the essential amino acid tryptophan to kynurenine is emerging as a potential key pathway involved in post-cardiac arrest brain injury. The aim of this study was to evaluate the effects of the modulation of kynurenine pathway on cardiac arrest outcome through genetic deletion of the rate-limiting enzyme of the pathway, indoleamine 2,3-dioxygenase. METHODS: Wild-type and indoleamine 2,3-dioxygenase-deleted (IDO-/-) mice were subjected to 8-min cardiac arrest. Survival, neurologic outcome, and locomotor activity were evaluated after resuscitation. Brain magnetic resonance imaging with diffusion tensor and diffusion-weighted imaging sequences was performed, together with microglia and macrophage activation and neurofilament light chain measurements. RESULTS: IDO-/- mice showed higher survival compared to wild-type mice (IDO-/- 11 of 16, wild-type 6 of 16, log-rank P = 0.036). Neurologic function was higher in IDO-/- mice than in wild-type mice after cardiac arrest (IDO-/- 9 ± 1, wild-type 7 ± 1, P = 0.012, n = 16). Indoleamine 2,3-dioxygenase deletion preserved locomotor function while maintaining physiologic circadian rhythm after cardiac arrest. Brain magnetic resonance imaging with diffusion tensor imaging showed an increase in mean fractional anisotropy in the corpus callosum (IDO-/- 0.68 ± 0.01, wild-type 0.65 ± 0.01, P = 0.010, n = 4 to 5) and in the external capsule (IDO-/- 0.47 ± 0.01, wild-type 0.45 ± 0.01, P = 0.006, n = 4 to 5) in IDO-/- mice compared with wild-type ones. Increased release of neurofilament light chain was observed in wild-type mice compared to IDO-/- (median concentrations [interquartile range], pg/mL: wild-type 1,138 [678 to 1,384]; IDO-/- 267 [157 to 550]; P < 0.001, n = 3 to 4). Brain magnetic resonance imaging with diffusion-weighted imaging revealed restriction of water diffusivity 24 h after cardiac arrest in wild-type mice; indoleamine 2,3-dioxygenase deletion prevented water diffusion abnormalities, which was reverted in IDO-/- mice receiving l-kynurenine (apparent diffusion coefficient, µm2/ms: wild-type, 0.48 ± 0.07; IDO-/-, 0.59 ± 0.02; IDO-/- and l-kynurenine, 0.47 ± 0.08; P = 0.007, n = 6). CONCLUSIONS: The kynurenine pathway represents a novel target to prevent post-cardiac arrest brain injury. The neuroprotective effects of indoleamine 2,3-dioxygenase deletion were associated with preservation of brain white matter microintegrity and with reduction of cerebral cytotoxic edema.

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.

The effect of blood pressure on mortality following out-of-hospital cardiac arrest: a retrospective cohort study of the United Kingdom Intensive Care National Audit and Research Centre database.

BACKGROUND: Hypotension following out-of-hospital cardiac arrest (OHCA) may cause secondary brain injury and increase mortality rates. Current guidelines recommend avoiding hypotension. However, the optimal blood pressure following OHCA is unknown. We hypothesised that exposure to hypotension and hypertension in the first 24 h in ICU would be associated with mortality following OHCA. METHODS: We conducted a retrospective analysis of OHCA patients included in the Intensive Care National Audit and Research Centre Case Mix Programme from 1 January 2010 to 31 December 2019. Restricted cubic splines were created following adjustment for important prognostic variables. We report the adjusted odds ratio for associations between lowest and highest mean arterial pressure (MAP) and systolic blood pressure (SBP) in the first 24 h of ICU care and hospital mortality. RESULTS: A total of 32,349 patients were included in the analysis. Hospital mortality was 56.2%. The median lowest and highest MAP and SBP were similar in survivors and non-survivors. Both hypotension and hypertension were associated with increased mortality. Patients who had a lowest recorded MAP in the range 60-63 mmHg had the lowest associated mortality. Patients who had a highest recorded MAP in the range 95-104 mmHg had the lowest associated mortality. The association between SBP and mortality followed a similar pattern to MAP. CONCLUSIONS: We found an association between hypotension and hypertension in the first 24 h in ICU and mortality following OHCA. The inability to distinguish between the median blood pressure of survivors and non-survivors indicates the need for research into individualised blood pressure targets for survivors following OHCA.

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.

Inflammatory response after out-of-hospital cardiac arrest-Impact on outcome and organ failure development.

BACKGROUND: Post-cardiac arrest syndrome that occurs in out-of-hospital cardiac arrest (OHCA) patients is characterized by inflammatory response. We conducted a scoping review of current evidence regarding several inflammatory markers' usefulness for assessment of patient outcome and illness severity. We also discuss the proposed underlying mechanisms leading to inflammatory response after OHCA. METHODS: We searched the MEDLINE, PubMed Central, Cochrane CENTRAL and Web of Science Core Collection databases with the following search terms: ("inflammation" OR "cytokines") AND "out-of-hospital cardiac arrest." Each inflammatory marker found was combined with "out-of-hospital cardiac arrest" using "AND" to find further relevant studies. We included original studies measuring inflammatory markers in adult OHCA patients that assessed their prognostic capabilities for mortality, neurological outcome, or organ failure severity. RESULTS: Fifty-nine studies met the inclusion criteria, covering in total 65 different markers. Interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were the most studied markers, and they were associated with poor outcomes in 13/15, 13/14 and 11/17 studies, respectively. Based on area under the receiver operating characteristic curve (AUC) value, the time point of best discriminatory capacity for poor outcome was ICU admission for IL-6 (median AUC 0.78, range 0.71-0.98) and day one after OHCA for PCT (median AUC 0.84, range 0.61-0.98). Seven studies reported AUCs for CRP (range 0.52-0.76) with no measurement time point being superior to others. The association of IL-6 and PCT with outcome appeared stronger in studies with more severely ill patients. Studies reported conflicting results regarding each marker's association with organ failure severity. CONCLUSION: Inflammatory markers are potentially useful for early risk stratification after OHCA. PCT and IL-6 have moderate prognostic value during the first 24 h of the ICU stay. Predictive accuracy appears to be associated with the study overall event rate.

Ubiquitin C-terminal hydrolase L1 after out-of-hospital cardiac arrest.

BACKGROUND: We studied the prognostic ability of serum ubiquitin C-terminal hydrolase L1 (UCH-L1) after out-of-hospital cardiac arrest (OHCA), compared to that of neuron-specific enolase (NSE). METHODS: In this post-hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH-L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010-2011. We evaluated the ability of UCH-L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3-5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. RESULTS: The concentrations of UCH-L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5-18.5 ng/mL) versus 7.8 ng/mL (5.9-11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2-27.7 ng/mL) versus 11.5 ng/mL (9.0-17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH-L1 as a 12-month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60-0.73) at 24 h and 0.66 (0.59-0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59-0.73) at 24 h and 0.72 (0.65-0.80) at 48 h. The prognostic ability of UCH-L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23). CONCLUSION: Concentrations of UCH-L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH-L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.

Markers of neutrophil mediated inflammation associate with disturbed continuous electroencephalogram after out of hospital cardiac arrest.

BACKGROUND: Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia-reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48-hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6-month neurological outcome. METHODS: This is an observational, post hoc sub-study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU-treated adult OHCA survivors with initial shockable rhythm. We used grading of 48-hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6-month cerebral performance category (CPC) 1-2 as good and CPC 3-5 as poor long-term neurological outcome. We compared the prognostic value of biomarkers for 6-month neurological outcome to neurofilament light (NFL) measured at 48 h. RESULTS: Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48-hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25-8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30-4.21) were independently associated with poor 48-hour cEEG in a multivariable logistic regression model. Poor 6-month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6-month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6-month outcome in a multivariable logistic regression model with 48-hour NFL. CONCLUSION: Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long-term prognostication compared to 48-hour NFL.

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.

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.

Brain injury after cardiac arrest.

As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.

Brain Injury Biomarkers for Predicting Outcome After Cardiac Arrest.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Target temperature management following cardiac arrest: a systematic review and Bayesian meta-analysis.

BACKGROUND: Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. METHODS: Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). RESULTS: In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32-34 °C was 0.95 [95% CrI 0.78-1.09] for death and RR 0.93 [95% CrI 0.84-1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32-34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32-34 °C were the highest for an absolute risk reduction of 2-4% for death (28-53% chance) and unfavourable neurological outcome (63-78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%. CONCLUSIONS: The posterior probability distributions did not support the use of TTM at 32-34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90-180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

Acute ischemic stroke in a university hospital intensive care unit: 1-year costs and outcome.

BACKGROUND AND PURPOSE: Little is currently known about the cost-effectiveness of intensive care of acute ischemic stroke (AIS). We evaluated 1-year costs and outcome for patients with AIS treated in the intensive care unit (ICU). MATERIALS AND METHODS: A single-center retrospective study of patients admitted to an academic ICU with AIS between 2003 and 2013. True healthcare expenditure was obtained up to 1 year after admission and adjusted to consumer price index of 2019. Patient outcome was 12-month functional outcome and mortality. We used multivariate logistic regression analysis to identify independent predictors of favorable outcomes and linear regression analysis to assess factors associated with costs. We calculated the effective cost per survivor (ECPS) and effective cost per favorable outcome (ECPFO). RESULTS: The study population comprised 154 patients. Reasons for ICU admission were: decreased consciousness level (47%) and need for respiratory support (40%). There were 68 (44%) 1 year survivors, of which 27 (18%) had a favorable outcome. High age (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.91-0.98) and high hospital admission National Institutes of Health Stroke Scale score (OR 0.92, 95% CI 0.87-0.97) were independent predictors of poor outcomes. Increased age had a cost ratio of 0.98 (95% CI 0.97-0.99) per added year. The ECPS and ECPFO were 115,628€ and 291,210€, respectively. CONCLUSIONS: Treatment of AIS in the ICU is resource-intense, and in an era predating mechanical thrombectomy the outcome is often poor, suggesting a need for further research into cost-efficacy of ICU care for AIS patients.

Electrolyte profiles with induced hypothermia: A sub study of a clinical trial evaluating the duration of hypothermia after cardiac arrest.

BACKGROUND: Electrolyte disturbances can result from targeted temperature treatment (TTM) in out-of-hospital cardiac arrest (OHCA) patients. This study explores electrolyte changes in blood and urine in OHCA patients treated with TTM. METHODS: This is a sub-study of the TTH48 trial, with the inclusion of 310 unconscious OHCA patients treated with TTM at 33°C for 24 or 48 h. Over a three-day period, serum concentrations were obtained on sodium potassium, chloride, ionized calcium, magnesium and phosphate, as were results from a 24-h diuresis and urine electrolyte concentration and excretion. Changes over time were analysed with a mixed-model multivariate analysis of variance with repeated measurements. RESULTS: On admission, mean ± SD sodium concentration was 138 ± 3.5 mmol/l, which increased slightly but significantly (p < .05) during the first 24 h. Magnesium concentration stayed within the reference interval. Median ionized calcium concentration increased from 1.11 (IQR 1.1-1.2) mmol/l during the first 24 h (p < .05), whereas median phosphate concentration dropped to 1.02 (IQR 0.8-1.2) mmol/l (p < .05) and stayed low. During rewarming, potassium concentrations increased, and magnesium and ionizes calcium concentration decreased (p < .05). Median 24-h diuresis results on days one and two were 2198 and 2048 ml respectively, and the electrolyte excretion mostly stayed low in the reference interval. CONCLUSIONS: Electrolytes mostly remained within the reference interval. A temporal change occurred in potassium, magnesium and calcium concentrations with TTM's different phases. No hypothermia effect on diuresis was detected, and urine excretion of electrolytes mostly stayed low.

Protocol for an individual patient data meta-analysis on blood pressure targets after cardiac arrest.

BACKGROUND: Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. METHODS: This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65-70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. CONCLUSIONS: This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences.

Early thrombocytopenia is associated with an increased risk of mortality in patients with traumatic brain injury treated in the intensive care unit: a Finnish Intensive Care Consortium study.

BACKGROUND: Coagulopathy after traumatic brain injury (TBI) is associated with poor prognosis. PURPOSE: To assess the prevalence and association with outcomes of early thrombocytopenia in patients with TBI treated in the intensive care unit (ICU). METHODS: This is a retrospective multicenter study of adult TBI patients admitted to ICUs during 2003-2019. Thrombocytopenia was defined as a platelet count < 100 × 109/L during the first day. The association between thrombocytopenia and hospital and 12-month mortality was tested using multivariable logistic regression, adjusting for markers of injury severity. RESULTS: Of 4419 patients, 530 (12%) had early thrombocytopenia. In patients with thrombocytopenia, hospital and 12-month mortality were 26% and 48%, respectively; in patients with a platelet count > 100 × 109/L, they were 9% and 22%, respectively. After adjusting for injury severity, a higher platelet count was associated with decreased odds of hospital mortality (OR 0.998 per unit, 95% CI 0.996-0.999) and 12-month mortality (OR 0.998 per unit, 95% CI 0.997-0.999) in patients with moderate-to-severe TBI. Compared to patients with a normal platelet count, patients with thrombocytopenia not receiving platelet transfusion had an increased risk of 12-month mortality (OR 2.2, 95% CI 1.6-3.0), whereas patients with thrombocytopenia receiving platelet transfusion did not (OR 1.0, 95% CI 0.6-1.7). CONCLUSION: Early thrombocytopenia occurs in approximately one-tenth of patients with TBI treated in the ICU, and it is an independent risk factor for mortality in patients with moderate-to-severe TBI. Further research is necessary to determine whether this is modifiable by platelet transfusion.

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.