Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Trends in the Utilization of Multiorgan Support Among Adults Undergoing High-risk Cardiac Surgery in the United States.

OBJECTIVES: To examine trends in the prevalence of multiorgan dysfunction (MODS), utilization of multi-organ support (MOS), and mortality among patients undergoing cardiac surgery with MODS who received MOS in the United States. DESIGN: Retrospective cohort study. SETTING: 183 hospitals in the Premier Healthcare Database. PARTICIPANTS: Adults ≥18 years old undergoing high-risk elective or non-elective cardiac surgery. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: The exposure was time (consecutive calendar quarters) January 2008 and June 2018. We analyzed hospital data using day-stamped hospital billing codes and diagnosis and procedure codes to assess MODS prevalence, MOS utilization, and mortality. Among 129,102 elective and 136,190 non-elective high-risk cardiac surgical cases across 183 hospitals, 10,001 (7.7%) and 21,556 (15.8%) of patients developed MODS, respectively. Among patients who experienced MODS, 2,181 (22%) of elective and 5,425 (25%) of non-elective cardiac surgical cases utilized MOS. From 2008-2018, MODS increased in both high-risk elective and non-elective cardiac surgical cases. Similarly, MOS increased in both high-risk elective and non-elective cardiac surgical cases. As a component of MOS, mechanical circulatory support (MCS) increased over time. Over the study period, risk-adjusted mortality, in patients who developed MODS receiving MOS, increased in high-risk non-elective cardiac surgery and decreased in high-risk elective cardiac surgery, despite increasing MODS prevalence and MOS utilization (p<0.001). CONCLUSIONS: Among patients undergoing high-risk cardiac surgery in the United States, MODS prevalence and MOS utilization (including MCS) increased over time. Risk-adjusted mortality trends differed in elective and non-elective cardiac surgery. Further research is necessary to optimize outcomes among patients undergoing high-risk cardiac surgery.

Hospital Outcomes in Patients Who Developed Acute Respiratory Distress Syndrome After Community-Acquired Pneumonia.

Purpose: To identify risk factors for and outcomes in acute respiratory distress syndrome (ARDS) in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a retrospective study using the Premier Healthcare Database between 2016 and 2020. Patients diagnosed with pneumonia, requiring mechanical ventilation (MV), antimicrobial therapy, and hospital admission ≥2 days were included. Multivariable regression models were used for outcomes including in-hospital mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, and days on MV. Results: 1924 (2.7%) of 72 107 patients with CAP developed ARDS. ARDS was associated with higher mortality (33.7% vs 18.9%; adjusted odds ratio 2.4; 95% confidence interval [CI] 2.16-2.66), longer hospital LOS (13 vs 9 days; adjusted incidence risk ratio (aIRR) 1.24; 95% CI 1.20-1.27), ICU LOS (9 vs 5 days; aIRR 1.51; 95% CI 1.46-1.56), more MV days (8 vs 5; aIRR 1.54; 95% CI 1.48-1.59), and increased hospitalization cost ($46 459 vs $29 441; aIRR 1.50; 95% CI 1.45-1.55). Conclusion: In CAP, ARDS was associated with worse in-patient outcomes in terms of mortality, LOS, and hospitalization cost. Future studies are needed to explore outcomes in patients with CAP with ARDS and explore risk factors for development of ARDS after CAP.

Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. OBJECTIVE: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. METHODS: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. RESULTS: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB- group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. CONCLUSION: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population.

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States. METHODS: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes. RESULTS: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66). CONCLUSIONS: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.

Safety, Efficacy, and Clinical Outcomes of Dexmedetomidine for Sedation in Traumatic Brain Injury: A Scoping Review.

Dexmedetomidine is a promising alternative sedative agent for moderate-severe Traumatic brain injury (TBI) patients. Although the data are limited, the posited benefits of dexmedetomidine in this population are a reduction in secondary brain injury compared with current standard sedative regimens. In this scoping review, we critically appraised the literature to examine the effects of dexmedetomidine in patients with moderate-severe TBI to examine the safety, efficacy, and cerebral and systemic physiological outcomes within this population. We sought to identify gaps in the literature and generate directions for future research. Two researchers and a librarian queried PubMed, Embase, Scopus, and APA PsycINFO databases. Of 920 studies imported for screening, 11 were identified for inclusion in the review. The primary outcomes in the included studied were cerebral physiology, systemic hemodynamics, sedation levels and delirium, and the presence of paroxysmal sympathetic hyperactivity. Dexmedetomidine dosing ranged from 0.2 to 1 ug/kg/h, with 3 studies using initial boluses of 0.8 to 1.0 ug/kg over 10 minutes. Dexmedetomidine used independently or as an adjunct seems to exhibit a similar hemodynamic safety profile compared with standard sedation regimens, albeit with transient episodes of bradycardia and hypotension, decrease episodes of agitation and may serve to alleviate symptoms of sympathetic hyperactivity. This scoping review suggests that dexmedetomidine is a safe and efficacious sedation strategy in patients with TBI. Given its rapid onset of action and anxiolytic properties, dexmedetomidine may serve as a feasible sedative for TBI patients.

Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Pulmonary Hypertension.

BACKGROUND: Patients with pulmonary hypertension have a high risk of maternal morbidity and mortality. It is unknown if a trial of labor carries a lower risk of morbidity in these patients compared to a planned cesarean delivery. The objective of this study was to examine the association of delivery mode with severe maternal morbidity events during delivery hospitalization among patients with pulmonary hypertension. METHODS: This retrospective cohort study used the Premier inpatient administrative database. Patients delivering ≥25 weeks gestation from January 1, 2016, to September 30, 2020, and with pulmonary hypertension were included. The primary analysis compared intended vaginal delivery (ie, trial of labor) to intended cesarean delivery (intention to treat analysis). A sensitivity analysis was conducted comparing vaginal delivery to cesarean delivery (as treated analysis). The primary outcome was nontransfusion severe maternal morbidity during the delivery hospitalization. Secondary outcomes included blood transfusion (4 or more units) and readmission to the delivery hospital within 90 days from discharge from delivery hospitalization. RESULTS: The cohort consisted of 727 deliveries. In the primary analysis, there was no difference in nontransfusion morbidity between intended vaginal delivery and intended cesarean delivery groups (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.49-1.15). In secondary analyses, intended cesarean delivery was not associated with blood transfusion (aOR, 0.71; 95% CI, 0.34-1.50) or readmission within 90 days (aOR, 0.60; 95% CI, 0.32-1.14). In the sensitivity analysis, cesarean delivery was associated with a 3-fold higher risk of nontransfusion morbidity compared to vaginal delivery (aOR, 2.64; 95% CI, 1.54-3.93), a 3-fold higher risk of blood transfusion (aOR, 3.06; 95% CI, 1.17-7.99), and a 2-fold higher risk of readmission within 90 days (aOR, 2.20; 95% CI, 1.09-4.46) compared to vaginal delivery. CONCLUSIONS: Among pregnant patients with pulmonary hypertension, a trial of labor was not associated with a higher risk of morbidity compared to an intended cesarean delivery. One-third of patients who required an intrapartum cesarean delivery had a morbidity event, demonstrating the increased risk of adverse events in this group.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Malnutrition and Adverse Outcomes After Surgery for Head and Neck Cancer.

Importance: Patients with head and neck cancer (HNC) have an increased risk of malnutrition, partly due to disease location and treatment sequelae. Although malnutrition is associated with adverse outcomes, there is little data on the extent of outcomes and the sociodemographic factors associated with malnutrition in patients with HNC. Objectives: To investigate the association of race, ethnicity, and payer type with perioperative malnutrition in patients undergoing HNC surgery and how malnutrition affects clinical outcomes. Design, Setting, and Participants: This retrospective cohort study used data from the Premier Healthcare Database to assess adult patients who had undergone HNC surgery from January 2008 to June 2020 at 482 hospitals across the US. Diagnosis and procedure codes were used to identify a subset of patients with perioperative malnutrition. Patient characteristics, payer types, and hospital outcomes were then compared to find associations among race, ethnicity, payer type, malnutrition, and clinical outcomes using multivariable logistic regression models. Analyses were performed from August 2022 to January 2023. Exposures: Race, ethnicity, and payer type for primary outcome, and perioperative malnutrition status, race, ethnicity, and payer type for secondary outcomes. Main Outcomes and Measures: Perioperative malnutrition status. Secondary outcomes were discharge to home after surgery, hospital length of stay (LOS), total cost, and postoperative pulmonary complications (PPCs). Results: The study population comprised 13 895 adult patients who had undergone HNC surgery during the study period; they had a mean (SD) age of 63.4 (12.1) years; 9425 male (67.8%) patients; 968 Black (7.0%), 10 698 White (77.0%), and 2229 (16.0%) individuals of other races; and 887 Hispanic (6.4%) and 13 008 non-Hispanic (93.6%) individuals. Among the total sample, there were 3136 patients (22.6%) diagnosed with perioperative malnutrition. Compared with White patients and patients with private health insurance, the odds of malnutrition were higher for non-Hispanic Black patients (adjusted odds ratio [aOR], 1.31; 95% CI, 1.11-1.56), Medicaid-insured patients (aOR, 1.68; 95% CI, 1.46-1.95), and Medicare-insured patients (aOR, 1.24; 95% CI, 1.10-1.73). Black patients and patients insured by Medicaid had increased LOS, costs, and PPCs, and lower rates of discharge to home. Malnutrition was independently associated with increased LOS (ß, 5.20 additional days; 95% CI, 4.83-5.64), higher costs (ß, $15 722 more cost; 95% CI, $14 301-$17 143), increased odds of PPCs (aOR, 2.04; 95% CI, 1.83-2.23), and lower odds of discharge to home (aOR, 0.34; 95% CI, 0.31-0.38). No independent association between malnutrition and mortality was observed. Conclusions and Relevance: This retrospective cohort study found that 1 in 5 patients undergoing HNC surgery were malnourished. Malnourishment disproportionately affected Black patients and patients with Medicaid, and contributed to longer hospital stays, higher costs, and more postoperative complications.

Change to Mixed-Lipid Emulsion From Soybean Oil-Based Lipid Emulsion in Pediatric Patients.

Importance: Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. Objective: To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes. Design, Setting, and Participants: Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023. Exposure: In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil-based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group). Main Outcomes and Measures: Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin). Results: A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant. Conclusions and Relevance: In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy-LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.

The Quality Improvement Fellow: Educating on Making the Difference.

The critical care medicine (CCM) fellowship is an opportunity for advanced anesthesiology trainees to refine their quality improvement (QI) skills. However, the short training period and inconsistent curricula make this challenging. The QI fellow (QIF) is described as an education program to provide consistent QI training during the CCM fellowship. The QIF is a mentored position to help manage data review, QI conferences, and improvement efforts within the CCM Division. The curriculum is focused on a QI education framework and mentored experiential learning. The QIF program is an opportunity for education and mentorship in the role of a CCM operational leader.

Early enteral nutrition is associated with improved outcomes in critically ill mechanically ventilated medical and surgical patients.

BACKGROUND AND AIMS: Data suggest that guidelines for enteral nutrition (EN) initiation are not closely followed in clinical practice. In addition, critically ill mechanically ventilated (MV) patients have varying metabolic needs, which often increase and persist over time, requiring personalized nutrition intervention. While both over- and under-nutrition can impact patient outcomes, recent data suggest that targeted early EN delivery may reduce mortality and improve clinical outcomes. This study examined if early EN improves clinical outcomes and decreases costs in critically ill patients on MV. METHODS: Data from a nationwide administrative-financial database between 2018 and 2020 was utilized to identify eligible adult critical care patients. Patients who received EN within 3 days after intubation (early EN) were compared to patients who started EN after 3 days of intubation (late EN). Outcomes of interest included hospital mortality, discharge disposition, hospital and intensive care unit (ICU) length of stay (LOS), MV days, and total cost. After inverse-probability-of-treatment weighting, outcomes were modeled using a nominal logistic regression model for hospital mortality and discharge disposition, a linear regression model for cost, and Cox proportional-hazards model for MV days, hospital and ICU LOS. RESULTS: A total of 27,887 adult patients with early MV were identified, of which 16,772 (60.1%) received early EN. Regression analyses showed that the early EN group had lower hospital mortality (OR = 0.88, 95% CI, 0.82 to 0.94), were more likely to be discharged home (OR = 1.47, 95% CI 1.38 to 1.56), had fewer MV days (HR = 1.23, 95% CI, 1.11 to 1.37), shorter hospital LOS (HR = 1.43, 95% CI, 1.33 to 1.54) and ICU LOS (HR = 1.36, 95% CI, 1.27 to 1.46), and lower cost (-$21,226; 95% CI, -$23,605 to -$18,848) compared to the late EN group. CONCLUSIONS: Early EN within 3 days of MV initiation in real-world practice demonstrated improved clinical and economic outcomes. These data suggest that early EN is associated with decreased hospital mortality, increased discharge to home, and decreased hospital and ICU LOS, time on MV, and cost compared to delayed initiation of EN; highlighting the importance of early EN to optimize utcomes ando support the recovery of critically ill patients on MV.

Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. INTERVENTIONS: None. MEASUREMENTS: Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. MAIN RESULTS: Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes. CONCLUSIONS: About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.

Epidemiology, Resistance Profiles, and Outcomes of Bloodstream Infections in Community-Onset Sepsis in the United States.

OBJECTIVES: To describe frequency of positive blood cultures, patterns of pathogens' characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. DESIGN: Retrospective cohort study. SETTING: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. SUBJECTS: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales /extended-spectrum ß-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85-0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78-0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa , methicillin-sensitive Staphylococcus aureus , and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli , Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. CONCLUSIONS: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

Opioid-Sparing Multimodal Analgesia Use After Cesarean Delivery Under General Anesthesia: A Retrospective Cohort Study in 729 US Hospitals.

BACKGROUND: Optimizing analgesia after cesarean delivery is essential to quality of patient recovery. The American Society of Anesthesiologists and the Society for Obstetric Anesthesia and Perinatology recommend multimodal analgesia (MMA). However, little is known about clinical implementation of these guidelines after cesarean delivery under general anesthesia (GA). We performed this study to describe the use of MMA after cesarean delivery under GA in the United States and determine factors associated with use of MMA, variation in analgesia practice across hospitals, and trends in MMA use over time. METHODS: A retrospective cohort study of women over 18 years who had a cesarean delivery under GA between 2008 and 2018 was conducted using the Premier Healthcare database (Premier Inc). The primary outcome was utilization of opioid-sparing MMA (osMMA), defined as receipt of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen with or without opioids and without the use of an opioid-combination drug. Any use of either agent within a combination preparation was not considered osMMA. The secondary outcome was use of optimal opioid-sparing MMA (OosMMA), defined as use of a local anesthetic technique such as truncal block or local anesthetic infiltration in addition to osMMA. Mixed-effects logistic regression models were used to examine factors associated with use of osMMA, as well as variation across hospitals. RESULTS: A total of 130,946 patients were included in analysis. osMMA regimens were used in 11,133 patients (8.5%). Use of osMMA increased from 2.0% in 2008 to 18.8% in 2018. Black race (7.9% vs 9.3%; odds ratio [OR] [95% confidence interval {CI}] 0.87 [0.81-0.94]) and Hispanic ethnicity (8.6% vs 10.0%; OR, 0.86 [0.79-0.950]) were associated with less receipt of osMMA compared to White and non-Hispanic counterparts. Medical comorbidities were generally not associated with receipt of osMMA, although patients with preeclampsia were less likely to receive osMMA (9.0%; OR, 0.91 [0.85-0.98]), while those with a history of drug abuse (12.5%; OR, 1.42 [1.27-1.58]) were more likely to receive osMMA. There was moderate interhospital variability in the use of osMMA (intraclass correlation coefficient = 38%). OosMMA was used in 2122 (1.6%) patients, and utilization increased from 0.8% in 2008 to 4.1% in 2018. CONCLUSIONS: Variation in osMMA utilization was observed after cesarean delivery under GA in this cohort of US hospitals. While increasing trends in utilization of osMMA and OosMMA are encouraging, there is need for increased attention to postoperative analgesia practices after GA for cesarean delivery given low percentage of patients receiving osMMA and OosMMA.

Maternal Cardiovascular Morbidity Events Following Preeclampsia: A Retrospective Cohort Study.

BACKGROUND: Patients with preeclampsia are at high risk for long-term cardiovascular events, yet the short-term, acute cardiovascular complications that follow preeclampsia are understudied. The objective of this study was to compare the short-term, acute maternal cardiovascular morbidity events after delivery among patients with a diagnosis of preeclampsia versus those without this diagnosis. METHODS: In this retrospective cohort study, the Premier inpatient database was used to examine a cohort of obstetric patients older than 18 years, who delivered from January 1, 2016, to September 30, 2020. A diagnosis of preeclampsia and preeclampsia with severe features during delivery hospitalization were the exposures of interest. The primary outcome was a composite of maternal cardiovascular morbidity events during delivery hospital admission. The secondary outcome was the occurrence of maternal cardiovascular morbidity events during a readmission within 90 days of delivery hospitalization. RESULTS: In total, 4,488,759 patients met inclusion criteria, of which 158,114 (3.5%) were diagnosed with preeclampsia without severe features, and 117,940 (2.6%) with preeclampsia with severe features. Adjusted odds of maternal cardiovascular morbidity events were higher in patients with preeclampsia and in those with preeclampsia with severe features compared with those without preeclampsia during delivery hospitalization (adjusted odds ratio [OR] [95% confidence interval {CI}] 1.87 [1.78-1.97] and 4.74 [4.44-5.05], respectively) and within 90 days (adjusted OR [95% CI] 2.01 [1.83-2.21] and 2.32 [2.10-2.57], respectively). CONCLUSIONS: Patients with both preeclampsia and preeclampsia with severe features have higher rates of maternal cardiovascular morbidity events than those without preeclampsia. Future studies are necessary to examine which patients with preeclampsia are at highest risk for cardiovascular complications.

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US.

Importance: Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. Objective: To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. Design, Setting, and Participants: This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Exposures: Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Main Outcomes and Measures: Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Results: Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). Conclusions and Relevance: In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Association of Brain Injury Biomarkers and Circulatory Shock Following Moderate-Severe Traumatic Brain Injury: A TRACK-TBI Study.

INTRODUCTION: Early circulatory shock following traumatic brain injury (TBI) is a multifactorial process; however, the impact of brain injury biomarkers on the risk of shock has not been evaluated. We examined the association between neuronal injury biomarker levels and the development of circulatory shock following moderate-severe TBI. METHODS: In this retrospective cohort study, we examined adults with moderate-severe TBI (Glasgow Coma Scale score <13) enrolled in the TRACK-TBI study, an 18-center prospective TBI cohort study. The exposures were day-1 levels of neuronal injury biomarkers (glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1 [UCH-L1], S100 calcium-binding protein B [S100B], neuron-specific enolase), and of an inflammatory biomarker (high-sensitivity C-reactive protein). The primary outcome was the development of circulatory shock, defined as cardiovascular Sequential Organ Failure Assessment Score ≥2 within 72 hours of admission. Association between day-1 biomarker levels and the development of circulatory shock was assessed with regression analysis. RESULTS: The study included 392 subjects, with a mean age of 40 years; 314 (80%) were male and 165 (42%) developed circulatory shock. Median (interquartile range) day-1 levels of UCH-L1 (994.8 [518.7 to 1988.2] pg/mL vs. 548.1 [280.2 to 1151.9] pg/mL; P <0.0001) and S100B (0.47 µg/mL [0.25 to 0.88] vs. 0.27 [0.16 to 0.46] µg/mL; P <0.0001) were elevated in those who developed early circulatory shock compared with those who did not. In multivariable regression, there were associations between levels of both UCH-L1 (odds ratio, 1.63 [95% confidence interval, 1.25-2.12]; P <0.0005) and S100B (odds ratio, 1.73 [95% confidence interval 1.27-2.36]; P <0.0005) with the development of circulatory shock. CONCLUSION: Neuronal injury biomarkers may provide the improved mechanistic understanding and possibly early identification of patients at risk for early circulatory shock following moderate-severe TBI.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.