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.

OXYGEN CONSUMPTION AS AN EARLY WARNING SYSTEM IN THE CRITICALLY ILL.

ABSTRACT: Introduction: In this study, we assessed whether changes in oxygen consumption (VO 2 ) and other metabolic parameters could be used as an early warning system for detecting clinical deterioration in mechanically ventilated patients. Methods: This was a prospective cohort study of adult patients requiring mechanical ventilation between February 2016 and March 2019. We looked for changes in VO 2 , carbon dioxide production (VCO 2 ), respiratory quotient (RQ), and end-tidal carbon dioxide (EtCO 2 ), occurring prior to clinical deterioration. Clinical deterioration was predefined as a requirement of vasopressor, an increase in serum lactate by 20% where at least one value was above 3 mmol/L, or a decrease in hemoglobin by 20% in the 4 hours prior to clinical deterioration. Results A total of 141 patients were included. There were no detectable changes in VO 2 , VCO 2 , and EtCO 2 within the 4 hours prior to any clinical deterioration. RQ increased significantly within the 4 hours prior to an increase in lactate as compared with no increase in lactate, but there were no detectable changes prior to other clinical deteriorations. Conclusions RQ has the potential to be an early marker of tissue hypoperfusion or mitochondrial dysfunction. However, future studies are necessary to evaluate the use of RQ as a bedside monitor in critical care settings.

Bicarbonate, calcium, and magnesium for in-hospital cardiac arrest - An instrumental variable analysis.

INTRODUCTION: Bicarbonate, calcium, and magnesium are commonly used during in-hospital cardiac arrest. Whether these drugs are associated with survival in cardiac arrest patients is uncertain. METHODS: This was an observational study using data from the Get With The Guidelines registry. Adult patients with an in-hospital cardiac arrest between January 2008 and December 2021 were included. An instrumental variable approach was used based on hospital preferences for bicarbonate, calcium, and magnesium, respectively. The primary outcome was survival to hospital discharge. RESULTS: A total of 319,230 patients were included. The median age was 66 years, 59% patients were male, and 85% patients presented with a non-shockable rhythm. Bicarbonate was administered in 58% patients, calcium in 33% patients, and magnesium in 10% patients. When considering drug use in the previous cardiac arrest patient at a given hospital as an instrument, the absolute difference in survival to hospital discharge was estimated at -14.2% (95% CI, -19.9 to -8.6) for bicarbonate, -3.0% (95% CI, -8.6 to 2.6) for calcium, and 10.7% (95% CI, -0.8 to 22.2) for magnesium as compared to no drug. When considering the proportion of drug use within the past year at a given hospital as an instrument, the confidence intervals were very wide, making the results difficult to interpret. CONCLUSIONS: In this analysis, the results for bicarbonate, calcium, and magnesium were inconclusive due to wide confidence intervals and inconsistencies in estimates across instrumental variables. Randomized trials are needed to investigate the effect of these drugs on patient outcomes.

Temperature control after adult cardiac arrest: An updated systematic review and meta-analysis.

AIM: To perform an updated systematic review and meta-analysis on temperature control in adult patients with cardiac arrest. METHODS: The review is an update of a previous systematic review published in 2021. An updated search including PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed on May 31, 2023. Controlled trials in humans were included. The population included adult patients with cardiac arrest. The review included all aspects of temperature control including timing, temperature, duration, method of induction and maintenance, and rewarming. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Certainty of evidence was evaluated using GRADE. RESULTS: The updated systematic search identified six new trials. Risk of bias in the trials was assessed as intermediate for most of the outcomes. For temperature control with a target of 32-34 °C vs. normothermia or 36 °C, two new trials were identified, with seven trials included in an updated meta-analysis. Temperature control with a target of 32-34 °C did not result in an improvement in survival (risk ratio: 1.06 [95%CI: 0.91, 1.23]) or favorable neurological outcome (risk ratio: 1.27 [95%CI: 0.89, 1.81]) at 90-180 days after the cardiac arrest (low certainty evidence). Subgroup analysis according to location of cardiac arrest (in-hospital vs. out-of-hospital) found similar results. A sensitivity analysis of nine trials comparing temperature control at 32-34 °C to normothermia or 36 °C for favorable neurological outcome at any time point also did not show an improvement in outcomes (risk ratio: 1.14 [95%CI 0.98, 1.34]). New individual trials comparing a target of 31-34 °C, temperature control for 12-24 hours to 36 hours, a rewarming rate of 0.25-0.5 °C/hour, and the effect of temperature control with fever prevention found no differences in outcomes. CONCLUSIONS: This updated systematic review showed no benefit of temperature control at 32-34 °C compared to normothermia or 36 °C, although the 95% confidence intervals cannot rule out a potential beneficial effect. Important knowledge gaps exist for topics such as hypothermic temperature targets, rewarming rate, and fever control.

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.

Kidney-specific biomarkers for predicting acute kidney injury following cardiac arrest.

AIM: To evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine. METHODS: Adult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge. RESULTS: Of 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all). CONCLUSION: In post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.

Extracorporeal Cardiopulmonary Resuscitation for Cardiac Arrest.

This JAMA Insights Clinical Update discusses the newer treatment option of extracorporeal cardiopulmonary resuscitation, particularly for patients with cardiac arrest who are not responsive to initial treatment.

Characteristics and Outcomes of Cardiac Arrest in Adult Patients Admitted to Pediatric Services: A Descriptive Analysis of the American Heart Association's Get With The Guidelines-Resuscitation Data.

OBJECTIVES: Differences between adult and pediatric in-hospital cardiac arrest (IHCA) are well-described. Although most adults are cared for on adult services, pediatric services often admit adults, particularly those with chronic conditions. The objective of this study is to describe IHCA in adults admitted to pediatric services. DESIGN: Retrospective cohort analysis from the American Heart Association's Get With The Guidelines-Resuscitation registry of a subpopulation of adults with IHCA while admitted to pediatric services. Multivariable logistic regression was used to evaluate adjusted survival outcomes and compare outcomes between age groups (18-21, 22-25, and ≥26 yr old). SETTING: Hospitals contributing to the Get With The Guidelines-Resuscitation registry. PATIENTS: Adult-aged patients (≥ 18 yr) with an index pulseless IHCA while admitted to a pediatric service from 2000 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 491 adult IHCAs were recorded on pediatric services at 17 sites, during the 19 years of review, and these events represented 0.1% of all adult IHCAs. In total, 221 cases met inclusion criteria with 139 events excluded due to an initial rhythm of bradycardia with poor perfusion. Median patient age was 22 years (interquartile range, 19-28 yr). Ninety-eight percent of patients had at least one pre-existing condition. Return of spontaneous circulation occurred in 63% of events and 30% of the patients survived to discharge. All age groups had similar rates of survival to discharge (range 26-37%; p = 0.37), and survival did not change over the study period (range 26-37%; p = 0.23 for adjusted survival to discharge). CONCLUSIONS: In this cohort of adults with IHCA while admitted to a pediatric service, we failed to find an association between survival outcomes and age. Additional research is needed to better understand resuscitation in this population.

Extracorporeal cardiopulmonary resuscitation for cardiac arrest: An updated systematic review.

OBJECTIVES: To provide an updated systematic review on the use of extracorporeal cardiopulmonary resuscitation (ECPR) compared with manual or mechanical cardiopulmonary resuscitation during cardiac arrest. METHODS: This was an update of a systematic review published in 2018. OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized trials and observational studies between January 1, 2018, and June 21, 2022. The population included adults and children with out-of-hospital or in-hospital cardiac arrest. Two investigators reviewed studies for relevance, extracted data, and assessed bias. The certainty of evidence was evaluated using GRADE. RESULTS: The search identified 3 trials, 27 observational studies, and 6 cost-effectiveness studies. All trials included adults with out-of-hospital cardiac arrest and were terminated before enrolling the intended number of subjects. One trial found a benefit of ECPR in survival and favorable neurological status, whereas two trials found no statistically significant differences in outcomes. There were 23 observational studies in adults with out-of-hospital cardiac arrest or in combination with in-hospital cardiac arrest, and 4 observational studies in children with in-hospital cardiac arrest. Results of individual studies were inconsistent, although many studies favored ECPR. The risk of bias was intermediate for trials and critical for observational studies. The certainty of evidence was very low to low. Study heterogeneity precluded meta-analyses. The cost-effectiveness varied depending on the setting and the analysis assumptions. CONCLUSIONS: Recent randomized trials suggest potential benefit of ECPR, but the certainty of evidence remains low. It is unclear which patients might benefit from ECPR.

Adjustment for Baseline Characteristics in Randomized Clinical Trials.

This Guide to Statistics and Methods provides an overview of the use of adjustment for baseline characteristics in the analysis of randomized clinical trials and emphasizes several important considerations.

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.

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial. METHODS: Patients aged ≥18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life. RESULTS: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals. CONCLUSIONS: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov-number, NCT04153435.

Socioeconomic status and outcomes after in-hospital cardiac arrest.

AIM: To investigate the association between socioeconomic status and outcomes after in-hospital cardiac arrest in Denmark. METHODS: We conducted an observational cohort study based on nationwide registries and prospectively collected data on in-hospital cardiac arrest from 2017 and 2018 in Denmark. Unadjusted and adjusted analyses using regression models were performed to assess the association between socioeconomic status and outcomes after in-hospital cardiac arrest. Outcomes included return of spontaneous circulation (ROSC), survival to 30 days, survival to one year, and the duration of resuscitation among patients without ROSC. RESULTS: A total of 3,223 patients with in-hospital cardiac arrest were included in the study. In the adjusted analyses, high household assets were associated with 1.20 (95 %CI: 0.96, 1.51) times the odds of ROSC, 1.49 (95 %CI: 1.14, 1.96) times the odds of survival to 30 days, 1.40 (95 %CI: 1.04, 1.90) times the odds of survival to one year, and 2.8 (95 %CI: 0.9, 4.7) minutes longer duration of resuscitation among patients without ROSC compared to low household assets. Similar albeit attenuated associations were observed for education. While high household income was associated with better outcomes in the unadjusted analyses, these associations largely disappeared in the adjusted analyses. CONCLUSIONS: In this study of patients with in-hospital cardiac arrest, we found that high household assets were associated with a higher odds of survival and a longer duration of resuscitation among patients without ROSC compared to low household assets. However, the effect size may potentially be small. The results varied based on socioeconomic status measure, outcome of interest, and across adjusted analyses.

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.

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.