Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis.

BACKGROUND: Tracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation. METHODS: We searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework ( https://osf.io/2vf79/ ). RESULTS: We included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79-1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes. CONCLUSIONS: All of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.

Left Main Bronchus Obstruction in a Patient with Small-cell Lung Cancer Successfully Treated with Venovenous Extracorporeal Membrane Oxygenation.

Lung cancer can cause fatal central airway obstruction. Rapid airway clearance is necessary in some cases, but ventilator management may be insufficient to maintain oxygenation levels. Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be an effective rescue therapy for respiratory failure, but its efficacy in treating tumor-related airway obstruction is unknown. We herein report a case of central airway obstruction and severe acute respiratory failure due to small-cell lung cancer successfully treated with VV-ECMO, bronchoscopic airway intervention, and chemotherapy. VV-ECMO can be an effective option for the treatment of central airway obstruction with acute respiratory failure due to lung cancer.

Hospital-onset sepsis and community-onset sepsis in critical care units in Japan: a retrospective cohort study based on a Japanese administrative claims database.

BACKGROUND: Hospital- and community-onset sepsis are significant sepsis subgroups. Japanese data comparing these subgroups are limited. This study aimed to describe the epidemiology of hospital- and community-onset sepsis in critical care units in Japan. METHODS: We performed a retrospective cohort study using the Japanese Diagnosis and Procedure Combination database. Adult patients admitted to critical care units with sepsis from April 2010 to March 2020 were included. Sepsis cases were identified based on ICD-10 codes for infectious diseases, procedure codes for blood culture tests, and medication codes for antimicrobials. Patients' characteristics, in-hospital mortality, and resource utilization were assessed. The in-hospital mortality between groups was compared using the Poisson regression generalized linear mixed-effect model. RESULTS: Of 516,124 patients, 52,183 (10.1%) had hospital-onset sepsis and 463,940 (89.9%) had community-onset sepsis. Hospital-onset sepsis was characterized by younger age, infrequent emergency hospitalization, frequent surgery under general anesthesia, and frequent organ support upon critical care unit admission compared to community-onset sepsis. In-hospital mortality was higher for hospital-onset than for community-onset sepsis (35.5% versus 19.2%; unadjusted mean difference, 16.3% [95% confidence interval (CI) 15.9-16.7]; adjusted mean difference, 15.6% [95% CI 14.9-16.2]). Mean hospital length of stay was longer for hospital-onset than for community-onset sepsis (47 days versus 30 days; unadjusted mean difference, 17 days [95% CI 16-17]; adjusted mean difference, 13 days [95% CI 12-14]). CONCLUSION: Patients with hospital-onset sepsis admitted to critical care units in Japan had a poorer prognosis and more resource utilization including organ support rate, number of days with critical care unit surcharge codes, and hospital length of stay than those with community-onset sepsis.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis.

Introduction: Antimicrobial dose optimization for the treatment of sepsis remains challenging because of dynamic pharmacokinetic alterations and physiological/pathological responses of the host. Subtherapeutic plasma levels of antimicrobials are commonly observed in patients with sepsis, which potentially leads to both treatment failure and emergence of antimicrobial resistance. The knowledge of antimicrobial pharmacokinetics and pharmacodynamics is helpful in order to tailor antimicrobial dosing strategies.Areas covered: This narrative review summarizes pharmacokinetic alterations of antimicrobial agents and provides useful information on antimicrobial dose optimization. Literature was searched using PubMed database, focusing on pharmacokinetics and pharmacodynamics of antibacterial and antifungal agents in sepsis.Expert opinion: In patients with sepsis, increased volume of distribution and variable changes in renal clearance are the two major factors for antimicrobial pharmacokinetic alterations. Traditional 'one-dose-fits-all' dosing strategy is not suitable for patients with sepsis and hence individualized antimicrobial dosing adjustment is preferable. In general, the initial dose of hydrophilic antimicrobials such as ß-lactams, aminoglycosides, and vancomycin should be given at a high dose regardless of renal function. Improved methods of drug administration (e.g. extended/continuous infusion of ß-lactams) help to increase the chance of pharmacodynamic target attainment. The use of therapeutic drug monitoring should be considered where available.

Intermittent Hemodialysis for Managing Metabolic Acidosis During Resuscitation of Septic Shock: A Descriptive Study.

Septic shock is often complicated by severe metabolic acidosis, for which renal replacement therapy may be considered. However, little is known about the use of intermittent hemodialysis to manage this condition. The aim of this study was to compare physiologic and biochemical variables and vasopressor requirements before and after intermittent hemodialysis among patients who received intermittent hemodialysis to manage metabolic acidosis during resuscitation of septic shock. DESIGN: This retrospective, cross-sectional study was conducted between April 2014 and September 2015. SETTINGS: The ICU of a non-university-affiliated teaching hospital. PATIENTS: Patients who were admitted to the ICU with septic shock and underwent intermittent hemodialysis to manage metabolic acidosis within 48 hours after the diagnosis of septic shock. MEASUREMENTS AND MAIN RESULTS: The main outcomes were mean arterial pressure, minute ventilator volume, norepinephrine requirement, bicarbonate and pH before and after intermittent hemodialysis. Of 1,190 patients screened, 34 were included, and 33 accomplished a planned session of intermittent hemodialysis. After intermittent hemodialysis, an increased mean arterial pressure (+9.0 mm Hg; 95% CI, 6-13; p < 0.001), decreased minute ventilatory volume (-2.0 L/min; 95% CI, -3.3 to 0.8; p = 0.002), decreased norepinephrine requirement (-0.07 µg/kg/min; 95% CI, -0.12 to -0.02; p = 0.009), increased bicarbonate level (+7.2 mmol/L; 95% CI, 6.1-8.3; p < 0.001), and increased pH (+0.17; 95% CI, 0.13-0.21; p < 0.001) were observed in comparison to those before intermittent hemodialysis. CONCLUSIONS: In conclusion, intermittent hemodialysis appeared to be feasible and to stabilize hemodynamic and respiratory conditions in patients with septic shock complicated by metabolic acidosis during resuscitation.