2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Sodium Bicarbonate and Calcium Chloride for the Treatment of Hyperkalemia-Induced Cardiac Arrest: A Randomized, Blinded, Placebo-Controlled Animal Study.

OBJECTIVES: Current international guidelines recommend administrating calcium chloride and sodium bicarbonate to patients with hyperkalemia-induced cardiac arrest, despite limited evidence. The aim of this study was to evaluate the efficacy of calcium chloride and sodium bicarbonate on return of spontaneous circulation (ROSC) in a pig model of hyperkalemia-induced cardiac arrest. DESIGN: A randomized, blinded, placebo-controlled experimental pig study. Hyperkalemia was induced by continuous infusion of potassium chloride over 45 minutes followed by a bolus. After a no flow period of 7 minutes, pigs first received 2 minutes of basic cardiopulmonary resuscitation and subsequently advanced life support. The first intervention dose was administered after the fifth rhythm analysis, followed by a defibrillation attempt at the sixth rhythm analysis. A second dose of the intervention was administered after the seventh rhythm analysis if ROSC was not achieved. In case of successful resuscitation, pigs received intensive care for 1 hour before termination of the study. SETTING: University hospital laboratory. SUBJECTS: Fifty-four female Landrace/Yorkshire/Duroc pigs (38-42 kg). INTERVENTIONS: The study used a 2 × 2 factorial design, with calcium chloride (0.1 mmol/kg) and sodium bicarbonate (1 mmol/kg) as the interventions. MEASUREMENTS AND MAIN RESULTS: Fifty-two pigs were included in the study. Sodium bicarbonate significantly increased the number of animals achieving ROSC (24/26 [92%] vs. 13/26 [50%]; odds ratio [OR], 12.0; 95% CI, 2.3-61.5; p = 0.003) and reduced time to ROSC (hazard ratio [HR] 3.6; 95% CI, 1.8-7.5; p < 0.001). There was no effect of calcium chloride on the number of animals achieving ROSC (19/26 [73%] vs. 18/26 [69%]; OR, 1.2; 95% CI, 0.4-4.0; p = 0.76) or time to ROSC (HR, 1.5; 95% CI, 0.8-2.9; p = 0.23). CONCLUSIONS: Administration of sodium bicarbonate significantly increased the number of animals achieving ROSC and decreased time to ROSC. There was no effect of calcium chloride on the number of animals achieving ROSC or time to ROSC.

Blood laboratory analyses preceding in-hospital cardiac arrest: A matched case-control study.

BACKGROUND: Whether blood laboratory analyses differ in patients who later suffer in-hospital cardiac arrest (IHCA) compared to other hospitalised patients remains unknown. The aim of this study was to describe pre-arrest sampling frequencies, results, and trends in blood laboratory analyses in patients with IHCA compared to controls. METHODS: This study was a matched case-control study using national registries in Denmark. Cases were defined as patients with IHCA from 2017 to 2021. Controls were defined as hospitalised patients and were matched on age, sex, and date and length of admission. Data on a total of 51 different blood laboratory analyses were obtained. The laboratory analyses of primary interest were lactate, sodium, potassium, and haemoglobin. The index time for cases was defined as the time of cardiac arrest, and a corresponding index time was defined for controls based on the time to cardiac arrest for their corresponding case. Blood sampling frequencies were reported for blood laboratory analyses obtained either within the last 24 h before the index time or between the time of hospital admission and the index time. Blood sampling results were reported for blood laboratory analyses obtained within the last 24 h before the index time. RESULTS: A total of 9268 cases and 92,395 controls were included in this study. Cases underwent more frequent sampling of all blood laboratory analyses compared to controls. This higher sampling frequency was more pronounced for lactate compared to sodium, potassium, or haemoglobin. The last measured lactate was higher in cases (median [IQR]: 2.3 [1.3, 4.9]) compared to controls (median [IQR]: 1.3 [0.9, 2.0]). Differences in sodium, potassium, and haemoglobin were negligible. The proportion of abnormally elevated levels of lactate and potassium increased as time to cardiac arrest decreased; no such effect was seen in controls. No temporal trend was evident for sodium or haemoglobin. CONCLUSIONS: Patients with IHCA undergo more frequent blood sampling prior to IHCA and have higher levels of lactate compared to matched controls.

2022 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

The effects of methylene blue during and after cardiac arrest in a porcine model; a randomized, blinded, placebo-controlled study.

PURPOSE: To evaluate the effect of methylene blue administered as a bolus on return of spontaneous circulation (ROSC), lactate levels, vasopressor requirements, and markers of neurological injury in a clinically relevant pig model of cardiac arrest. MATERIALS AND METHODS: 40 anesthetized pigs were subjected to acute myocardial infarction and 7 min of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (controls), one group received 2 mg/kg methylene blue and saline (MB + saline), and one group received two doses of 2 mg/kg methylene blue (MB + MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving ROSC. Animals underwent intensive care and observation for six hours, followed by cerebral magnetic resonance imaging (MRI). The primary outcome for this study was development in lactate levels after cardiac arrest. Categorical data were compared using Fisher's exact test and pointwise data were analyzed using one-way analysis of variance (ANOVA) or equivalent non-parametric test. Continuous data collected over time were analyzed using a linear mixed effects model. A value of p < .05 was considered statistically significant. RESULTS: Lactate levels increased in all groups after cardiac arrest and resuscitation, however lactate levels in the MB + MB group decreased significantly faster compared with the control group (p = .007) and the MB + saline group (p = .02). The proportion of animals achieving initial ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB + saline group, and 12/14 (86%) in the MB + MB group (p = .81). Time to ROSC did not differ between groups (p = .67). There was no significant difference in accumulated norepinephrine dose between groups (p = .15). Cerebral glycerol levels were significantly lower in the MB + MB group after resuscitation compared with control group (p = .03). However, MRI data revealed no difference in apparent diffusion coefficient, cerebral blood flow, or dynamic contrast enhanced MR perfusion between groups. CONCLUSION: Treatment with a bolus of methylene blue during cardiac arrest and after resuscitation did not significantly improve hemodynamic function. A bolus of methylene blue did not yield the neuroprotective effects that have previously been described in animals receiving methylene blue as an infusion.

Patient-Important Outcomes Other Than Mortality in Contemporary ICU Trials: A Scoping Review.

OBJECTIVES: Randomized clinical trials (RCTs) conducted in adult ICU patients increasingly include patient-important outcomes other than mortality. This comes with challenges regarding outcome choices/definitions, handling of deceased patients and missing data in analyses, and choices of effect measures and statistical methods due to complex distributions. This scoping review aimed to characterize how these challenges are handled in relevant contemporary RCTs. DATA SOURCES: We systematically searched 10 selected journals for RCTs conducted primarily in adult ICU patients published between 1 January 2018 and 5 May 2022 reporting at least one patient-important outcome other than mortality, including "days alive without"…-type outcomes, functional/cognitive/neurologic outcomes, health-related quality of life (HRQoL) outcomes, and ordinal/other outcomes. STUDY SELECTION: Abstracts and full-texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined and pilot-tested extraction forms and subsequently categorized to facilitate analysis. DATA SYNTHESIS: We included 687 outcomes from 167 RCTs, with 32% of RCTs using a patient-important outcome other than mortality as a (co-)primary outcome, most frequently "days alive without"…-type outcomes. Many different functional/cognitive/neurologic (103) and HRQoL (29) outcomes were reported. Handling of deceased patients varied, with analyses frequently restricted to survivors only for functional/cognitive/neurologic (62%) and HRQoL (89%) outcomes. Follow-up was generally longer and missing data proportions higher for functional/cognitive/neurologic and HRQoL outcomes. Most outcomes were analyzed using nonparametric tests (31%), linear regression/ t tests (27%), chi-square-like tests (12%), and proportional odds logistic regression (9%), often without presentation of actual treatment effects estimates (38%). CONCLUSIONS: In this sample of RCTs, substantial variation in practice and suboptimal methodological choices were observed. This calls for increased focus on standardizing outcome choices and definitions, adequate handling of missing data and deceased patients in analyses, and use of statistical methods quantifying effect sizes.

Goal-directed haemodynamic therapy during general anaesthesia for noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: During general anaesthesia for noncardiac surgery, there remain knowledge gaps regarding the effect of goal-directed haemodynamic therapy on patient-centred outcomes. METHODS: Included clinical trials investigated goal-directed haemodynamic therapy during general anaesthesia in adults undergoing noncardiac surgery and reported at least one patient-centred postoperative outcome. PubMed and Embase were searched for relevant articles on March 8, 2021. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. The primary outcomes were mortality and hospital length of stay, whereas 15 postoperative complications were included based on availability. From a main pool of comparable trials, meta-analyses were performed on trials with homogenous outcome definitions. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). RESULTS: The main pool consisted of 76 trials with intermediate risk of bias for most outcomes. Overall, goal-directed haemodynamic therapy might reduce mortality (odds ratio=0.84; 95% confidence interval [CI], 0.64 to 1.09) and shorten length of stay (mean difference=-0.72 days; 95% CI, -1.10 to -0.35) but with low certainty in the evidence. For both outcomes, larger effects favouring goal-directed haemodynamic therapy were seen in abdominal surgery, very high-risk surgery, and using targets based on preload variation by the respiratory cycle. However, formal tests for subgroup differences were not statistically significant. Goal-directed haemodynamic therapy decreased risk of several postoperative outcomes, but only infectious outcomes and anastomotic leakage reached moderate certainty of evidence. CONCLUSIONS: Goal-directed haemodynamic therapy during general anaesthesia might decrease mortality, hospital length of stay, and several postoperative complications. Only infectious postoperative complications and anastomotic leakage reached moderate certainty in the evidence.

Ventilation Strategies During General Anesthesia for Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal ventilation strategy during general anesthesia is unclear. This systematic review investigated the relationship between ventilation targets or strategies (eg, positive end-expiratory pressure [PEEP], tidal volume, and recruitment maneuvers) and postoperative outcomes. METHODS: PubMed and Embase were searched on March 8, 2021, for randomized trials investigating the effect of different respiratory targets or strategies on adults undergoing noncardiac surgery. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and several subgroup analyses were conducted. The certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This review included 63 trials with 65 comparisons. Risk of bias was intermediate for all trials. In the meta-analyses, lung-protective ventilation (ie, low tidal volume with PEEP) reduced the risk of combined pulmonary complications (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.28-0.49; 9 trials; 1106 patients), atelectasis (OR, 0.39; 95% CI, 0.25-0.60; 8 trials; 895 patients), and need for postoperative mechanical ventilation (OR, 0.36; 95% CI, 0.13-1.00; 5 trials; 636 patients). Recruitment maneuvers reduced the risk of atelectasis (OR, 0.44; 95% CI, 0.21-0.92; 5 trials; 328 patients). We found no clear effect of tidal volume, higher versus lower PEEP, or recruitment maneuvers on postoperative pulmonary complications when evaluated individually. For all comparisons across targets, no effect was found on mortality or hospital length of stay. No effect measure modifiers were found in subgroup analyses. The certainty of evidence was rated as very low, low, or moderate depending on the intervention and outcome. CONCLUSIONS: Although lung-protective ventilation results in a decrease in pulmonary complications, randomized clinical trials provide only limited evidence to guide specific ventilation strategies during general anesthesia for adults undergoing noncardiac surgery.

Hospital-level variation in outcomes after in-hospital cardiac arrest in Denmark.

BACKGROUND: We investigated hospital-level variation in outcomes after in-hospital cardiac arrest (IHCA) in Denmark, and assessed whether variation in outcomes could be explained by differences in patient characteristics. METHODS: Adult patients (≥18 years old) with IHCA in 2017 and 2018 were included from the Danish IHCA Registry (DANARREST). Data on patient characteristics and outcomes were obtained from population-based registries. Predicted probabilities, likelihood ratio tests, intraclass correlation coefficients (ICCs), and median odds ratios (ORs) were calculated for return of spontaneous circulation (ROSC), survival to 30 days, and survival to 1 year. RESULTS: A total of 3340 patients with IHCA from 24 hospitals were included. We found that hospital-level variation in outcomes after IHCA existed across all measures of variation. The unadjusted median OR for ROSC, survival to 30 days, and survival to 1 year were 1.28 (95% confidence interval [CI]: 1.24, 1.45), 1.38 (95% CI: 1.33, 1.60), and 1.44 (95% CI: 1.39, 1.70), respectively. The unadjusted ICC suggest that 2.0% (95%: 1.6%, 4.4%), 3.3% (95%: 2.7%, 6.8%), and 4.3% (95%: 3.5%, 8.6%) of the total individual variation in ROSC, survival to 30 days, and survival to 1 year was attributable to hospital-level variation. These results decreased but persisted in the analyses adjusted for select patient characteristics. CONCLUSIONS: In this study, we found that outcomes after IHCA varied across hospitals in Denmark. However, only about 2%-4% of the total individual variation in outcomes after IHCA was attributable to differences between hospitals, suggesting that most of the individual variation in outcomes was attributable to patient-level variation.

Fluid management of emergency department patients with sepsis-A survey of fluid resuscitation practices.

BACKGROUND: Fluid administration and resuscitation of patients with sepsis admitted through emergency departments (ED) remains a challenge, and evidence is sparse especially in sepsis patients without shock. We aimed to investigate emergency medicine physicians' and nurses' perceptions, self-reported decision-making and daily behavior, and challenges in fluid administration of ED sepsis patients. METHODS: We developed and conducted a multicenter, web-based, cross-sectional survey focusing on fluid administration to ED patients with sepsis sent to all nurses and physicians from the five EDs in the Central Denmark Region. The survey consisted of three sections: (1) baseline information; (2) perceptions of fluid administration and daily practice; and (3) clinical scenarios about fluid administration. The survey was performed from February to June, 2021. RESULTS: In total, 138 of 246 physicians (56%) and 382 of 595 nurses (64%) responded to the survey. Of total, 94% of physicians and 97% of nurses regarded fluid as an important part of sepsis treatment. Of total, 80% of physicians and 61% of nurses faced challenges regarding fluid administration in the ED, and decisions were usually based on clinical judgment. The most common challenge was the lack of guidelines for fluid administration. Of total, 96% agreed that they would like to learn more about fluid administration, and 53% requested research in fluid administration of patients with sepsis. For a normotensive patient with sepsis, 46% of physicians and 44% of nurses administered 1000 ml fluid in the first hour. Of total, 95% of physicians and 89% of nurses preferred to administer ≥1000 ml within an hour if the patients' blood pressure was 95/60 at admission. There was marked variability in responses. Blood pressure was the most commonly used trigger for fluid administration. Respondents preferred to administer less fluid if the patient in the scenario had known renal impairment or heart failure. Normal saline was the preferred fluid. CONCLUSION: Fluid administration is regarded as an important but challenging aspect of sepsis management. Responses to scenarios revealed variability in fluid volumes. Blood pressure was the most used trigger. ED nurses and physicians request evidence-based guidelines to improve fluid administration.

Intraoperative respiratory and hemodynamic strategies for reducing nausea, vomiting, and pain after surgery: Systematic review and meta-analysis.

BACKGROUND: Despite improved medical treatment strategies, postoperative pain, nausea, and vomiting remain major challenges. This systematic review investigated the relationship between perioperative respiratory and hemodynamic interventions and postoperative pain, nausea, and vomiting. METHODS: PubMed and Embase were searched on March 8, 2021 for randomized clinical trials investigating the effect of perioperative respiratory or hemodynamic interventions in adults undergoing non-cardiac surgery. Investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed when feasible. GRADE was used to assess the certainty of the evidence. RESULTS: This review included 65 original trials; of these 48% had pain, nausea, and/or vomiting as the primary focus. No reduction of postoperative pain was found in meta-analyses when comparing recruitment maneuvers with no recruitment, high (80%) to low (30%) fraction of oxygen, low (5-7 ml/kg) to high (9-12 ml/kg) tidal volume, or goal-directed hemodynamic therapy to standard care. In the meta-analysis comparing recruitment maneuvers with no recruitment maneuvers, patients undergoing laparoscopic gynecological surgery had less shoulder pain 24 h postoperatively (mean difference in the numeric rating scale from 0 to 10: -1.1, 95% CI: -1.7, -0.5). In meta-analyses, comparing high to low fraction of inspired oxygen and goal-directed hemodynamic therapy to standard care in patients undergoing abdominal surgery, the risk of postoperative nausea and vomiting was reduced (odds ratio: 0.45, 95% CI: 0.24, 0.87 and 0.48, 95% CI: 0.27, 0.85). The certainty in the evidence was mostly very low to low. The results should be considered exploratory given the lack of prespecified hypotheses and corresponding risk of Type 1 errors. CONCLUSION: There is limited evidence regarding the impact of intraoperative respiratory and hemodynamic interventions on postoperative pain or nausea and vomiting. More definitive trials are needed to guide clinical care within this area.

Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial.

BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO2 /FiO2 ratio in patients with COVID-19 and severe respiratory insufficiency. METHODS: Investigator-initiated, randomized, open-label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID-19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO2 /FiO2 ratio at 72 h. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non-invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7-71.2). The primary outcome, PaO2 /FiO2 ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference -5.1 kPa [95% CI -10.2, -0.04] p = .05). The 28-day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06-2.07, p = .26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO2 /FiO2 ratio at 72 h with no differences for other outcomes.

Fraction of inspired oxygen during general anesthesia for non-cardiac surgery: Systematic review and meta-analysis.

BACKGROUND: Controversy exists regarding the effects of a high versus a low intraoperative fraction of inspired oxygen (FiO2 ) in adults undergoing general anesthesia. This systematic review and meta-analysis investigated the effect of a high versus a low FiO2 on postoperative outcomes. METHODS: PubMed and Embase were searched on March 22, 2022 for randomized clinical trials investigating the effect of different FiO2 levels in adults undergoing general anesthesia for non-cardiac surgery. Two investigators independently reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and potential effect measure modification was assessed in subgroup analyses and meta-regression. The evidence certainty was evaluated using GRADE. RESULTS: This review included 25 original trials investigating the effect of a high (mostly 80%) versus a low (mostly 30%) FiO2 . Risk of bias was intermediate for all trials. A high FiO2 did not result in a significant reduction in surgical site infections (OR: 0.91, 95% CI 0.81-1.02 [p = .10]). No effect was found for all other included outcomes, including mortality (OR = 1.27, 95% CI: 0.90-1.79 [p = .18]) and hospital length of stay (mean difference = 0.03 days, 95% CI -0.25 to 0.30 [p = .84). Results from subgroup analyses and meta-regression did not identify any clear effect modifiers across outcomes. The certainty of evidence (GRADE) was rated as low for most outcomes. CONCLUSIONS: In adults undergoing general anesthesia for non-cardiac surgery, a high FiO2 did not improve outcomes including surgical site infections, length of stay, or mortality. However, the certainty of the evidence was assessed as low.

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.

Patient-important outcomes other than mortality in recent ICU trials: Protocol for a scoping review.

BACKGROUND: Randomised clinical trials (RCTs) conducted in intensive care units (ICUs) frequently focus on all-cause mortality, but other patient-important outcomes are increasingly used and recommended. Their use, however, is not straightforward: choices and definitions, operationalisation of death, handling of missing data, choice of effect measures, and statistical analyses for these outcomes vary greatly. METHODS: We will conduct a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We will search 10 selected general and speciality journals for RCTs conducted in adult ICU patients from 2018 and onwards reporting at least 1 patient-important outcome other than mortality (including days alive without life support/days alive and out of hospital-type outcomes, health-related quality of life, functional/cognitive/neurological outcomes, and other general patient-important outcomes). We will summarise data on outcome measures and definitions, assessment time points, proportions and handling of death, proportions and handling of missing data, and effect measures and statistical methods used for analysis. DISCUSSION: The outlined scoping review will provide an overview of choices, definitions and handling of patient-important outcomes other than mortality in contemporary RCTs conducted in adult ICU patients. This may guide discussions with patients and relatives, the design of future RCTs, and research on optimal outcome choices and handling.

Twenty-four-hour fluid administration in emergency department patients with suspected infection: A multicenter, prospective, observational study.

BACKGROUND: To describe 24-hour fluid administration in emergency department (ED) patients with suspected infection. METHODS: A prospective, multicenter, observational study conducted in three Danish hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. PRIMARY OUTCOME: 24-hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24-hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors. RESULTS: 734 patients had 24-hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24-hour fluid volumes were 3656 mL (standard deviation [SD]:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference [MD]: 60-79 years: -470 mL [95% CI: -789, -150], +80 years; -974 mL [95% CI: -1307, -640]), do-not-resuscitate orders (MD: -466 mL [95% CI: -797, -135]), and preexisting atrial fibrillation (MD: -367 mL [95% CI: -661, -72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL [95% CI: 820, 1543]), mean arterial pressure < 65 mmHg (MD: 1317 mL [95% CI: 770, 1864]), lactate ≥ 2 mmol/L (MD: 655 mL [95% CI: 306, 1005]), heart rate > 120 min (MD: 566 [95% CI: 169, 962]), low (MD: 1963 mL [95% CI: 813, 3112]) and high temperature (MD: 489 mL [95% CI: 234, 742]), SOFA score > 5 (MD: 1005 mL [95% CI: 501, 510]), and new-onset atrial fibrillation (MD: 498 mL [95% CI: 30, 965]) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients. CONCLUSIONS: Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest. Objective: To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021. Interventions: The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine. Main Outcomes and Measures: The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. Results: Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia. Conclusions and Relevance: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults. Trial Registration: ClinicalTrials.gov Identifier: NCT04153435.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Trends in Survival After Pediatric In-Hospital Cardiac Arrest in the United States.

BACKGROUND: Cardiac arrest in hospitalized children is associated with poor outcomes, but no contemporary study has reported whether the trends in survival have changed over time. In this study, we examined temporal trends in survival for pediatric patients with an in-hospital pulseless cardiac arrest and pediatric patients with a nonpulseless cardiopulmonary resuscitation event from 2000 to 2018. METHODS: This was an observational study of hospitalized pediatric patients (≤18 years of age) who received cardiopulmonary resuscitation from January 2000 to December 2018 and were included in the Get With The Guidelines-Resuscitation registry, a United States-based in-hospital cardiac arrest registry. The primary outcome was survival to hospital discharge, and the secondary outcome was return of spontaneous circulation (binary outcomes). Generalized estimation equations were used to obtain unadjusted trends in outcomes over time. Separate analyses were performed for patients with a pulseless cardiac arrest and patients with a nonpulseless event (bradycardia with poor perfusion) requiring cardiopulmonary resuscitation. A subgroup analysis was conducted for shockable versus nonshockable initial rhythms in pulseless events. RESULTS: A total of 7433 patients with a pulseless cardiac arrest and 5751 patients with a nonpulseless event were included for the analyses. For pulseless cardiac arrests, survival was 19% (95% CI, 11%-29%) in 2000 and 38% (95% CI, 34%-43%) in 2018, with an absolute change of 0.67% (95% CI, 0.40%-0.95%; P<0.001) per year, although the increase in survival appeared to stagnate following 2010. Return of spontaneous circulation also increased over time, with an absolute change of 0.83% (95% CI, 0.53%-1.14%; P<0.001) per year. We found no interaction between survival to hospital discharge and the initial rhythm. For nonpulseless events, survival was 57% (95% CI, 39%-75%) in 2000 and 66% (95% CI, 61%-72%) in 2018, with an absolute change of 0.80% (95% CI, 0.32%-1.27%; P=0.001) per year. CONCLUSIONS: Survival has improved for pediatric events requiring cardiopulmonary resuscitation in the United States, with a 19% absolute increase in survival for in-hospital pulseless cardiac arrests and a 9% absolute increase in survival for nonpulseless events between 2000 and 2018. However, survival from pulseless cardiac arrests appeared to have reached a plateau following 2010.