Intramuscular ketamine vs. midazolam for rapid risk-reduction in suicidal, depressed emergency patients: Clinical trial design and rationale.

Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED. A pre-injection phase involves screening, informed consent, eligibility confirmation, and baseline assessment of suicidal ideation, depression, and comorbidities. The randomized double-blind IM injection is administered in the ED under research staff supervision, vital sign monitoring, pharmacokinetic blood sampling, and clinical assessments. The post-injection phase occurs on a psychiatric inpatient unit with follow-up research assessments through four weeks post-discharge. Outcome measures are feasibility, safety, and effects on suicidal ideation and depression at 24 h post-injection, and through follow-up. The target sample is N = 90 adults in a major depressive episode, assessed by ED clinicians as warranting hospitalization for suicide risk. Here we report design, rationale, and preliminary feasibility and safety for this ongoing study. Demographics of the 53 participants (ages 18 to 65 years) randomized to date suggest a diverse sample tending towards younger adults.

Practice Patterns and Outcomes of Potassium Repletion Thresholds during Critical Illness.

Rationale: Potassium repletion is common in critically ill patients. However, practice patterns and outcomes related to different intensive care unit (ICU) potassium repletion strategies are unclear. Objectives: 1) Describe potassium repletion practices in critically ill adults; 2) compare the effectiveness of potassium repletion strategies; and 3) compare effectiveness and safety of specific potassium repletion thresholds on patient outcomes. Methods: This was a retrospective analysis of the PINC AI Healthcare Database (2016-2022), including all critically ill adults admitted to an ICU on Hospital Day 1 and with a serum potassium concentration measured on Hospital Day 2. We determined the frequency of potassium repletion (any formulation) at each measured serum potassium concentration in each ICU, then classified ICUs as having threshold-based (a large increase in potassium repletion rates at a specific serum potassium concentration) or probabilistic (linear relationship between serum concentration and the repletion probability) patterns of repletion. Between patients in threshold-based and probabilistic repletion ICUs, we compared outcomes (primary outcome: potassium repletion frequency). We reported unadjusted percentages per exposure group and the adjusted odds ratios (from hierarchical regression models) for each outcome. Among patients in threshold-based ICUs with the most common repletion thresholds (3.5 mEq/L and 4.0 mEq/L), we conducted regression discontinuity analyses to examine the effectiveness of potassium repletion at each potassium threshold. Results: We included 190,490 patients in 88 ICUs; 35.0% received at least one dose of potassium on the same calendar day. Rates of potassium repletion were similar between 22 threshold-based strategy ICUs (33.5%) and 22 probabilistic strategy ICUs (36.4%). There was no difference in the adjusted risk of potassium repletion between patients admitted to threshold-based strategy ICUs versus probabilistic strategy ICUs (adjusted odds ratio, 1.09; 95% confidence interval [CI], 0.76-1.57). In regression discontinuity analysis, crossing the 3.5 mEq/L threshold from high to low potassium levels resulted in a 39.1% (95% CI, 23.7-42.4) absolute increase in potassium repletion but no change in other outcomes. Similarly, crossing the 4.0 mEq/L threshold resulted in a 36.4% (95% CI, 22.4-42.2) absolute increase in potassium repletion but no change in other outcomes. Conclusions: Potassium repletion is common in critically ill patients and occurs over a narrow range of "normal" potassium levels (3.5-4.0 mEq/L); use of a threshold-based repletion strategy to guide potassium repletion in ICU patients is not associated with clinically meaningful differences in outcomes.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment, and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage, resuscitative endovascular balloon occlusion and resuscitative thoracotomy, pericardiocentesis, needle decompression, and thoracostomy. CONCLUSIONS: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition, and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well-organised team using crew resource management, but also on an institutional safety culture embedded in everyday practice through continuous education, training, and multidisciplinary co-operation.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council (ERC) guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage (OCCM), resuscitative endovascular balloon occlusion (REBOA) and resuscitative thoracotomy, pericardiocentesis, needle decompression and thoracostomy. CONCLUSION: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well organised team using crew resource management but also on an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary co-operation.

The Spillover Effects of Quality Improvement Beyond Target Populations in Mechanical Ventilation.

To assess the impact of a mechanical ventilation quality improvement program on patients who were excluded from the intervention. DESIGN: Before-during-and-after implementation interrupted time series analysis to assess the effect of the intervention between coronary artery bypass grafting (CABG) surgery patients (included) and left-sided valve surgery patients (excluded). SETTING: Academic medical center. PATIENTS: Patients undergoing CABG and left-sided valve procedures were analyzed. INTERVENTIONS: A postoperative mechanical ventilation quality improvement program was developed for patients undergoing CABG. MEASUREMENTS AND MAIN RESULTS: Patients undergoing CABG had a median mechanical ventilation time of 11 hours during P0 ("before" phase) and 6.22 hours during P2 ("after" phase; p < 0.001). A spillover effect was observed because mechanical ventilation times also decreased from 10 hours during P0 to 6 hours during P2 among valve patients who were excluded from the protocol (p < 0.001). The interrupted time series analysis demonstrated a significant level of change for ventilation time from P0 to P2 for both CABG (p < 0.0001) and valve patients (p < 0.0001). There was no significant difference in the slope of change between the CABG and valve patient populations across time cohorts (P0 vs P1 [p = 0.8809]; P1 vs P2 [p = 0.3834]; P0 vs P2 [p = 0.7672]), which suggests that the rate of change in mechanical ventilation times was similar between included and excluded patients. CONCLUSIONS: Decreased mechanical ventilation times for patients who were not included in a protocol suggests a spillover effect of quality improvement and demonstrates that quality improvement can have benefits beyond a target population.

Impact of Early, Low-Dose Factor VIIa on Subsequent Transfusions and Length of Stay in Cardiac Surgery.

OBJECTIVE: Recombinant factor VII (rFVIIa) is used to treat cardiac surgical bleeding in an off-label manner. However, optimal dosing and timing of administration to provide efficacious yet safe outcomes remain unknown. DESIGN: Retrospective, observational study. SETTING: Tertiary care academic center. PARTICIPANTS: Cardiac surgical patients (N = 214) who received low-dose rFVIIa for cardiac surgical bleeding. INTERVENTIONS: Patients were allocated into one of three groups based on timing of rFVIIa administration during the course of bleeding resuscitation based on the number of hemostatic products given before rFVIIa administration: group one = ≤one products (n = 82); group two = two-to-four products (n = 73); and group three= ≥five products (n = 59). MEASUREMENTS AND MAIN RESULTS: Patients who received low-dose rFVIIa later in the course of bleeding resuscitation (group three) had longer intensive care unit stays (p = 0.014) and increased incidence of postoperative renal failure when compared with group one (p = 0.039). Total transfusions were lowest in patients who received rFVIIa early in the course of resuscitation (group one) (median, two [interquartile range (IQR), 1-4.75]) and highest in group three (median, 11 [IQR, 8-14]; p < 0.001). Subsequent blood product transfusions after rFVIIa administration were highest in group two (p = 0.003); however, the median for all three groups was two products. There were no differences in thrombosis, reexplorations, or mortality in any of the groups. CONCLUSIONS: This study identified no differences in adverse outcomes based on timing of administration of low-dose rFVIIa for cardiac surgical bleeding defined by stage of resuscitation, but the benefits of early administration remain unclear.

Implementation of lung protective ventilation order to improve adherence to low tidal volume ventilation: A RE-AIM evaluation.

PURPOSE: Lung protective ventilation (LPV), defined as a tidal volume (Vt) ≤8 cc/kg of predicted body weight, reduces ventilator-induced lung injury but is applied inconsistently. MATERIALS AND METHODS: We conducted a prospective, quasi-experimental, cohort study of adults mechanically ventilated admitted to intensive care units (ICU) in the year before, year after, and second year after implementation of an electronic medical record based LPV order, and a cross-sectional qualitative study of ICU providers regarding their perceptions of the order. We applied the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate the implementation. RESULTS: There were 1405, 1424, and 1342 in the control, adoption, and maintenance cohorts, representing 95% of mechanically ventilated adult ICU patients. The overall prevalence of LPV increased from 65% to 73% (p < 0.001, adjusted-OR for LPV adherence: 1.9, 95% CI 1.5-2.3), but LPV adherence in women was approximately 30% worse than in men (women: 44% to 56% [p < 0.001],men: 79% to 86% [p < 0.001]). ICU providers noted difficulty obtaining an accurate height measurement and mistrust of the Vt calculation as barriers to implementation. LPV adherence increased further in the second year post implementation. CONCLUSION: We designed and implemented an LPV order that sustainably improved LPV adherence across diverse ICUs.

Association of Delirium With Long-term Cognitive Decline: A Meta-analysis.

Importance: Delirium is associated with increased hospital costs, health care complications, and increased mortality. Long-term consequences of delirium on cognition have not been synthesized and quantified via meta-analysis. Objective: To determine if an episode of delirium was an independent risk factor for long-term cognitive decline, and if it was, whether it was causative or an epiphenomenon in already compromised individuals. Data Sources: A systematic search in PubMed, Cochrane, and Embase was conducted from January 1, 1965, to December 31, 2018. A systematic review guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses was conducted. Search terms included delirium AND postoperative cognitive dysfunction; delirium and cognitive decline; delirium AND dementia; and delirium AND memory. Study Selection: Inclusion criteria for studies included contrast between groups with delirium and without delirium; an objective continuous or binary measure of cognitive outcome; a final time point of 3 or more months after the delirium episode. The electronic search was conducted according to established methodologies and was executed on October 17, 2018. Data Extraction and Synthesis: Three authors extracted data on individual characteristics, study design, and outcome, followed by a second independent check on outcome measures. Effect sizes were calculated as Hedges g. If necessary, binary outcomes were also converted to g. Only a single effect size was calculated for each study. Main Outcomes and Measures: The planned main outcome was magnitude of cognitive decline in Hedges g effect size in delirium groups when contrasted with groups that did not experience delirium. Results: Of 1583 articles, data subjected from the 24 studies (including 3562 patients who experienced delirium and 6987 controls who did not) were included in a random-effects meta-analysis for pooled effect estimates and random-effects meta-regressions to identify sources of study variance. One study was excluded as an outlier. There was a significant association between delirium and long-term cognitive decline, as the estimated effect size (Hedges g) for 23 studies was 0.45 (95% CI, 0.34-0.57; P < .001). In all studies, the group that experienced delirium had worse cognition at the final time point. The I2 measure of between-study variability in g was 0.81. A multivariable meta-regression suggested that duration of follow-up (longer with larger gs), number of covariates controlled (greater numbers were associated with smaller gs), and baseline cognitive matching (matching was associated with larger gs) were significant sources of variance. More specialized subgroup and meta-regressions were consistent with predictions that suggested that delirium may be a causative factor in cognitive decline. Conclusions and Relevance: In this meta-analysis, delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients.

Psychological distress, coping behaviors, and preferences for support among New York healthcare workers during the COVID-19 pandemic.

OBJECTIVE: The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. METHODS: This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th-April 24th 2020) at a large medical center in NYC (n = 657). RESULTS: Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. CONCLUSIONS: NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Initial Clinical Impressions of the Critical Care of COVID-19 Patients in Seattle, New York City, and Chicago.

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-now named coronavirus disease of 2019 (COVID-19)-have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020.In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

Sudden Cardiac Arrest Survivorship: A Scientific Statement From the American Heart Association.

Cardiac arrest systems of care are successfully coordinating community, emergency medical services, and hospital efforts to improve the process of care for patients who have had a cardiac arrest. As a result, the number of people surviving sudden cardiac arrest is increasing. However, physical, cognitive, and emotional effects of surviving cardiac arrest may linger for months or years. Systematic recommendations stop short of addressing partnerships needed to care for patients and caregivers after medical stabilization. This document expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac arrest survivorship.

The microbiome: implications for perioperative and critical care.

PURPOSE OF REVIEW: The host-microbiota relationship is integral in human health and can be rapidly disrupted in ways that may contribute to poor recovery from surgery or acute illness. We review key studies by organ system to understand the effect of perioperative and critical illness stress on the microbiota. Throughout the review, our focus is on potential interventions that may be mediated by the microbiome. RECENT FINDINGS: Although any perioperative intervention can have a profound impact on the gut microbiota, it is less clear how such changes translate into altered health outcomes. Preoperative stress (anxiety, lack of sleep, fasting), intraoperative stress (surgery itself, volatile anesthetics, perioperative antibiotics, blood transfusions), and postoperative stress (sepsis, surgical site infections, acute respiratory distress syndrome, catecholamines, antibiotics, opioids, proton pump inhibitors) have all been associated with alterations of the commensal microflora. These factors (e.g. administration of antibiotics or opioids) can create a favorable environment for emergence of pathogen virulence and development of serious infections and multiorgan failure. Data to recommend therapies aimed at restoring a disrupted microbiota, such as probiotics/prebiotics and fecal microbiota transplants is currently scarce. SUMMARY: The microbiome is likely to play an important role in the perioperative and ICU setting but existing data is largely descriptive. There is an expanding number of mechanistic studies that attempt to disentangle the complicated bi-directional relationship between the host and the resident microbiota. When these results are combined with ongoing clinical studies, we should be able to offer better therapies aimed at restoring the microbiota in the future.