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.

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.

Early myoclonus following anoxic brain injury.

BACKGROUND: It is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses. METHODS: In this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category. RESULTS: Patients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively). CONCLUSIONS: Cortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Cardiac Arrest in the Operating Room: Part 2-Special Situations in the Perioperative Period.

As noted in part 1 of this series, periprocedural cardiac arrest (PPCA) can differ greatly in etiology and treatment from what is described by the American Heart Association advanced cardiac life support algorithms, which were largely developed for use in out-of-hospital cardiac arrest and in-hospital cardiac arrest outside of the perioperative space. Specifically, there are several life-threatening causes of PPCA of which the management should be within the skill set of all anesthesiologists. However, previous research has demonstrated that continued review and training in the management of these scenarios is greatly needed and is also associated with improved delivery of care and outcomes during PPCA. There is a growing body of literature describing the incidence, causes, treatment, and outcomes of common causes of PPCA (eg, malignant hyperthermia, massive trauma, and local anesthetic systemic toxicity) and the need for a better awareness of these topics within the anesthesiology community at large. As noted in part 1 of this series, these events are always witnessed by a member of the perioperative team, frequently anticipated, and involve rescuer-providers with knowledge of the patient and the procedure they are undergoing or have had. Formulation of an appropriate differential diagnosis and rapid application of targeted interventions are critical for good patient outcome. Resuscitation algorithms that include the evaluation and management of common causes leading to cardiac in the perioperative setting are presented. Practicing anesthesiologists need a working knowledge of these algorithms to maximize good outcomes.

Cardiac Arrest in the Operating Room: Resuscitation and Management for the Anesthesiologist: Part 1.

Cardiac arrest in the operating room and procedural areas has a different spectrum of causes (ie, hypovolemia, gas embolism, and hyperkalemia), and rapid and appropriate evaluation and management of these causes require modification of traditional cardiac arrest algorithms. There is a small but growing body of literature describing the incidence, causes, treatments, and outcomes of circulatory crisis and perioperative cardiac arrest. These events are almost always witnessed, frequently known, and involve rescuer providers with knowledge of the patient and their procedure. In this setting, there can be formulation of a differential diagnosis and a directed intervention that treats the likely underlying cause(s) of the crisis while concurrently managing the crisis itself. Management of cardiac arrest of the perioperative patient is predicated on expert opinion, physiologic rationale, and an understanding of the context in which these events occur. Resuscitation algorithms should consider the evaluation and management of these causes of crisis in the perioperative setting.

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial.

OBJECTIVE: Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder. METHOD: In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1). RESULTS: The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen's d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine's effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up. CONCLUSIONS: Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect.