Vasopressin and methylprednisolone and hemodynamics after in-hospital cardiac arrest - A post hoc analysis of the VAM-IHCA trial.

INTRODUCTION: The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC. METHODS: The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin. RESULTS: The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs. CONCLUSION: Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.

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.

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.

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.

Effect of vasopressin and methylprednisolone vs. placebo on long-term outcomes in patients with in-hospital cardiac arrest a randomized clinical trial.

OBJECTIVE: The primary results from the Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial have previously been reported. The objective of the current manuscript is to report long-term outcomes. METHODS: The VAM-IHCA trial was a multicenter, randomized, double-blind, placebo-controlled trial conducted at ten hospitals in Denmark. Adult patients (age ≥ 18 years) were eligible for the trial if they had an in-hospital cardiac arrest and received at least one dose of epinephrine during resuscitation. The trial drugs consisted of 40 mg methylprednisolone (Solu-Medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of epinephrine. This manuscript report outcomes at 6 months and 1 year including survival, survival with favorable neurological outcome, and health-related quality of life. RESULTS: 501 patients were included in the analysis. At 1 year, 15 patients (6.3%) in the intervention group and 22 patients (8.3%) in the placebo group were alive corresponding to a risk ratio of 0.76 (95% CI, 0.41-1.41). A favorable neurologic outcome at 1 year, based on the Cerebral Performance Category score, was observed in 14 patients (5.9%) in the intervention group and 20 patients (7.6%) in the placebo group (risk ratio, 0.78 [95% CI, 0.41-1.49]. No differences existed between groups for favorable neurological outcome and health-related quality of life at either 6 months or 1 year. CONCLUSIONS: Administration of vasopressin and methylprednisolone, compared with placebo, in patients with in-hospital cardiac arrest did not improve long-term outcomes in this trial.

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.

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.

Age and sex differences in outcomes after in-hospital cardiac arrest.

INTRODUCTION: While specific factors have been associated with outcomes after in-hospital cardiac arrest, the association between sex and outcomes remains debated. Moreover, age-specific sex differences in outcomes have not been fully characterized in this population. METHODS: Adult patients (≥18 years) with an index in-hospital cardiac arrest were included from the Danish In-Hospital Cardiac Arrest Registry (DANARREST) from January 1st, 2017 to December 31st, 2018. Population-based registries were used to obtain data on patient characteristics, cardiac arrest characteristics, and outcomes. Unadjusted and adjusted estimates for return of spontaneous circulation (ROSC), survival to 30 days, survival to one year, duration of resuscitation, and post-cardiac arrest time-to-death were computed. RESULTS: A total of 3266 patients were included, of which 2041 (62%) patients were male with a median age of 73 years (quartiles: 64, 80). Among 1225 (38%) female patients, the median age was 76 years (quartiles: 67, 83). Younger age was associated with higher odds of ROSC and survival. Sex was not associated with ROSC and survival in the unadjusted analyses. In the adjusted analyses, women had 1.32 (95%CI: 1.12, 1.54) times the odds of survival to 30 days and 1.26 (95%CI: 1.02, 1.57) times the odds of survival to one year compared to men. The overall association between sex and survival did not vary substantially across age categories, although female sex was associated with a higher survival within certain age categories. Among patients who did not achieve ROSC, female sex was associated with a shorter duration of resuscitation, which was more pronounced in younger age categories. CONCLUSIONS: In this study of patients with in-hospital cardiac arrest, female sex was associated with a shorter duration of resuscitation among patients without ROSC but a higher survival to 30 days and one year. While the overall association between sex and outcomes did not vary substantially across age categories, female sex was associated with a higher survival within certain age categories.

Pulseless electrical activity vs. asystole in adult in-hospital cardiac arrest: Predictors and outcomes.

AIM: This observational cohort study aimed to identify factors associated with pulseless electrical activity (PEA) and asystole in in-hospital cardiac arrest (IHCA) patients and to determine whether differences in outcome based on the initial rhythm were explained by patient- and cardiac arrest characteristics. METHODS: Adults with IHCA from 2017 to 2018 were included from the Danish IHCA Registry (DANARREST). Additional data came from population-based registries. Unadjusted (RRs) and adjusted risk ratios (aRRs) were estimated for predictors of initial rhythm, return of spontaneous circulation (ROSC), and survival. RESULTS: We included 1495 PEA and 1285 asystole patients. The patients did not differ substantially in patient characteristics. Female sex, age>90 years, pulmonary disease, and obesity were associated with initial asystole. Ischemic heart disease and witnessed and monitored cardiac arrest were associated with initial PEA. In unadjusted and adjusted analyses, PEA was associated with increased ROSC (aRR = 1.21, 95% confidence interval [CI] 1.10; 1.33). PEA was also associated with increased 30-day and 1-year survival in the unadjusted analysis, while there was no clear association between the initial rhythm and 30-day (aRR = 0.88, 95% CI 0.71; 1.11) and 1-year (aRR = 0.85, 95% CI 0.69; 1.04) survival when patient- and cardiac arrest characteristics were adjusted for. CONCLUSION: In patients with IHCA presenting with PEA or asystole, there were no major differences in patient demographics and comorbidities. The patients differed substantially in cardiac arrest characteristics. Initial PEA was associated with higher risk of ROSC, but there was no difference in 30-day and 1-year survival.

Factors associated with shockable versus non-shockable rhythms in patients with in-hospital cardiac arrest.

AIM: To identify factors associated with the initial rhythm in patients with in-hospital cardiac arrest and to assess whether potential differences in outcomes based on the initial rhythm can be explained by patient and event characteristics. METHODS: Adult patients (≥18 years old) with in-hospital cardiac arrest in 2017 and 2018 were included from the Danish In-Hospital Cardiac Arrest Registry (DANARREST). We used population-based registries to obtain data on comorbidities, cardiac procedures, and medications. Unadjusted and adjusted risk ratios (RRs) for initial rhythm, return of spontaneous circulation (ROSC), and survival were estimated in separate models including an incremental number of prespecified variables. RESULTS: A total of 3422 patients with in-hospital cardiac arrest were included, of which 639 (19%) had an initial shockable rhythm. Monitored cardiac arrest, witnessed cardiac arrest, and specific cardiac diseases (i.e. ischemic heart disease, dysrhythmias, and valvular heart disease) were associated with initial shockable rhythm. Conversely, higher age, female sex, and specific non-cardiovascular comorbidities (e.g. overweight and obesity, renal disease, and pulmonary cancer) were associated with an initial non-shockable rhythm. Initial shockable rhythm remained strongly associated with increased ROSC (RR = 1.63, 95%CI 1.51-1.76), 30-day survival (RR = 2.31, 95%CI 2.02-2.64), and 1-year survival (RR = 2.36, 95%CI 2.02-2.76) compared to initial non-shockable rhythm in the adjusted analyses. CONCLUSION: In this study, specific patient and cardiac arrest characteristics were associated with initial rhythm in patients with in-hospital cardiac arrest. However, differences in patient and cardiac arrest characteristics did not fully explain the association with survival for initial shockable rhythm compared to a non-shockable rhythm.

In-Hospital vs. Out-of-Hospital Cardiac Arrest: Patient Characteristics and Survival.

BACKGROUND: Cardiac arrests are often categorized into two separate groups depending on the location of the arrest: in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA). Despite this distinction, few studies have compared the two groups directly. The aim of this study was to compare patient characteristics, cardiac arrest characteristics, and outcomes for IHCA and OHCA patients. METHODS: Data on IHCA and OHCA in Denmark were obtained from two nationwide, prospective registries. All adult (≥18 years old) patients with index IHCA or OHCA from January 1, 2017 to December 31, 2018 were included. Supplementary information on outcomes, hospitalizations, and chronic diseases came from additional national registries. The primary outcome was 30-day survival and secondary outcomes were return of spontaneous circulation (ROSC) and 1-year survival. RESULTS: The study included 3501 patients with IHCA and 8846 patients with OHCA. The two groups were similar in demographics, most comorbidities, and initial cardiac arrest rhythm. In the unadjusted analysis, IHCA was associated with increased survival to 30 days compared to OHCA (risk ratio [RR] = 1.41; 95% CI, 1.30; 1.54) and 1 year (RR = 1.46; 95% CI, 1.33; 1.61). Adjusting for age, sex, and comorbidities did not change the RR substantially. When cardiac arrest characteristics were added to the model, the RR decreased from 1.51 (95% CI, 1.39; 1.65) to 1.06 (95% CI, 0.93; 1.20) for survival to 30 days and from 1.66 (95% CI, 1.50; 1.84) to 1.09 (95% CI, 0.94; 1.26) for survival to 1 year. In all subgroup analyses based on cardiac arrest characteristics (e.g. witnessed status), the association between location and outcome was substantially mitigated compared to the primary analyses. CONCLUSIONS: In this large, national study, we found that IHCA and OHCA patients were remarkably similar in demographics and most comorbidities. IHCA patients had better outcomes compared to OHCA patients, although these differences disappeared when comparing patients with similar cardiac arrest characteristics.

Socioeconomic status and in-hospital cardiac arrest: A systematic review.

AIM: To perform a review of the literature on the association between socioeconomic status and risk of and outcomes after in-hospital cardiac arrest. DATA SOURCES: PubMed and Embase were searched on January 24, 2020 for studies evaluating the association between socioeconomic status and risk of and/or outcomes after in-hospital cardiac arrest. Two reviewers independently screened the titles/abstracts and selected full texts for relevance. Data were extracted from included studies. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool. RESULTS: The literature search yielded 4960 unique records. We included nine studies evaluating the association between socioeconomic status and risk of and/or outcomes after in-hospital cardiac arrest. All studies were observational cohort studies, of which seven were from the USA. Seven studies were in an adult population, while two studies were in a pediatric population. Results were overall inconsistent although some studies found a higher in-hospital cardiac arrest incidence in patients from low-income communities. There was no clear association between other socioeconomic factors (i.e. education, occupation, marital status, and insurance) and risk of or outcomes after in-hospital cardiac arrest. Due to the scarcity and heterogeneity of available studies, meta-analyses were not performed. CONCLUSION: There are limited data regarding the association between socioeconomic status and risk of and outcomes after in-hospital cardiac arrest and further research is warranted. Understanding the association between socioeconomic status and in-hospital cardiac arrest may reveal strategies to mitigate potential inequalities.

Adult post-cardiac arrest interventions: An overview of randomized clinical trials.

AIM: To provide an overview of published and registered trials related to post-cardiac arrest interventions. DATA SOURCE: We searched PubMed and the International Clinical Trials Registry Platform for randomized clinical trials in adults specifically addressing a post-cardiac arrest intervention. RESULTS: We identified 65 manuscripts reporting randomized clinical trials. The majority of the trials were published within the last 10 years and the sample sizes were generally low with a median of 90 participants (quartiles: 49, 262; range: 9, 1359). The majority of the trials were conducted in out-of-hospital cardiac arrest (79%), while only 6% were conducted specifically in in-hospital cardiac arrest and 15% included both in- and out-of-hospital cardiac arrest. We identified 48 registered trials online. The median target sample size is 100 participants (quartiles: 60, 400; range: 20, 1900). The majority of trials are enrolling patients with out-of-hospital cardiac arrest (71%) while 6% specifically focuses on in-hospital cardiac arrest. CONCLUSION: This review provides an overview of published and registered trials addressing post-cardiac arrest interventions. We believe this information will be relevant to guide future research.