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Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function. We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups. The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2. Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.

To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. Retrospective cohort study. A large multi-site health system with hospitals across the United States. Patients: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. None. Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71–2.20) or multivariable analysis (OR 1.34, 95% CI 0.68–2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37–16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74–12.18, p < 0.001). There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.

The new ultra-short-acting benzodiazepine, remimazolam, offers a pharmacokinetic and pharmacodynamic advantage over commonly used procedural sedation medication. This retrospective study explored the real-world utilization of remimazolam during procedural sedation to support the development of a nurse sedation protocol. The primary outcome was to identify associations between recovery time, adverse reactions, and dose-response in expanded patient populations. This study reviewed charts of 292 adult patients from 3 hospitals within one institution who received remimazolam during procedural sedation between June 1, 2021 and December 31, 2021. Data were analyzed using logistic and linear regression. The median time to alert in patients receiving remimazolam alone was 12 minutes (interquartile range 10, 17) and increased when additional sedation medications were utilized. Receiving additional sedative medication significantly increased the odds of hypoxia (OR 2.77, 95% CI 1.30–5.91, P = 0.008) after adjusting for body mass index (BMI), American Society of Anesthesiologists physical status (ASA-PS), and total remimazolam dose. There was a 25% increase in odds of experiencing hypoxia for every 5 kg/m2 increase in BMI (95% CI 1.01–1.54, P = 0.037). Remimazolam presents as a promising option for nurse procedural sedation, offering minimal impact on hemodynamics and respirations, quick recovery, and no residual sedative effects.

Acute pain accounts for over 70% of Emergency Department (ED) visits. Sub-dissociative dose ketamine (0.1–0.6 mg/kg) is safe and effective for the management of acute pain in the ED. However, the optimal dose of intravenous ketamine that provides effective analgesia and minimizes the risk of adverse effects has yet to be identified. The objective of this study was to describe an effective analgesia dose range of IV ketamine for acute pain in the ED. This multi-center, retrospective cohort study evaluated adult patients who received analgesic and sub-dissociative dose ketamine for the management of acute pain between May 5, 2018, and August 30, 2021, in 21 emergency departments at academic, community, and critical access hospitals across four states. Patients were excluded if they received ketamine for an indication other than pain, such as procedural sedation or intubation, or for whom there was incomplete documentation for the primary outcome. Patients who received a ketamine dose <0.3 mg/kg were stratified into the low-dose group, and those who received a dose of 0.3 mg/kg or higher to the high-dose group. The primary outcome was change in pain scores within 60 min using a standard 11-point numeric rating scale (NRS). Secondary outcomes included incidence of adverse effects and use of rescue analgesics. Continuous variables were compared between dose groups using student t-test or Wilcoxon Rank-Sum test. Linear regression was used to assess the association between the change in NRS pain scores within 60 min and dose after adjusting for baseline pain, requiring an additional dose of ketamine, and receiving an opioid. From 3796 patient encounters screened for receipt of ketamine, 384 patients met inclusion criteria including 258 in the low-dose group, and 126 in the high-dose group. The primary reason for exclusion was incomplete documentation of pain scores, or ketamine used for sedation. Median baseline pain scores were 8.2 in the low-dose group and 7.8 in the high-dose group (difference 0.5; 95% CI 0 to 1, p = 0.04). Both groups demonstrated significant reductions in their mean NRS pain scores within 60 min following the first administration of IV ketamine. There were no differences in the change in pain scores between both groups (−2.2 vs −2.6, mean difference 0.4, 95% CI -0.4 to 1.1, p = 0.34). Use of rescue analgesics (40.7% vs 36.5%, p = 0.43) and adverse effects were similar between groups, including early discontinuation of the ketamine infusion (37.2% vs. 37.3%, p = 0.99). Overall, the most common adverse effects were agitation (7.3%) and nausea (7.0%). The analgesic efficacy and safety of high-dose sub-dissociative ketamine (≥0.3 mg/kg) was not superior to low-dose (< 0.3 mg/kg) for the management of acute pain in the ED. Low-dose ketamine <0.3 mg/kg is an effective and safe pain management strategy in this population. •Ketamine is an opioid-sparing alternative for acute pain management.•The optimal dose of sub-dissociative ketamine for acute pain management has yet been identified.•The analgesic efficacy and safety of high-dose IV ketamine was not superior to low-dose IV ketamine.•IV ketamine doses >0.45 mg/kg further reduced pain, but also increased the risk of adverse effects.

Advances in surgical techniques have improved clinical outcomes and decreased complications. At the same time, heightened attention to care quality has resulted in increased identification of hospital-acquired adverse events. We evaluated these divergent effects on the reported safety of lung cancer resection. We analyzed hospital-acquired adverse events in patients undergoing lung cancer resection using the National Hospital Discharge Survey (NHDS) database from 2001-2010. Demographics, diagnoses, and procedures data were abstracted using ICD-9 codes. We used the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSI) to identify hospital-acquired adverse events. Weighted analyses were performed using t-tests and chi-square. A total of 302,444 hospitalizations for lung cancer resection and were included in the analysis. Incidence of PSI increased over time (28% in 2001-2002 vs 34% in 2009-2010; P<0.001). Those with one or more PSI had increased in-hospital mortality (aOR = 11.1; 95% CI, 4.7-26.1; P<0.001) and prolonged hospitalization (12.5 vs 7.8 days; P<0.001). However, among those with PSI, in-hospital mortality decreased over time, from 17% in 2001-2002 to 2% in 2009-2010. In a recent ten-year period, documented rates of adverse events associated with lung cancer resection increased. Despite this increase in safety events, we observed that mortality decreased. Because such metrics may be incorporated into hospital rankings and reimbursement considerations, adverse event coding consistency and content merit further evaluation.

Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability. •Patients commonly experience peri-intubation hypotension.•There are various vasopressor strategies to obtain mean arterial pressure.•Vasopressor selection should be patient specific.•No difference in cardiovascular instability with various vasopressor strategies.

To define outpatient parenteral antimicrobial therapy (OPAT) clinical pharmacy practice across the United States, specifically pharmacist functions, design of pharmacist involvement, and to compare pharmacist training of those who practice in OPAT to infectious diseases pharmacists who do not. A survey of a possible 32 questions was emailed to the American College of Clinical Pharmacists (ACCP) Infectious Diseases Practice and Research Network (PRN) e-mail list. Results were focused on US-based respondents. In total, 87 pharmacists responded; 27 of these pharmacists (31%) practiced in OPAT. Training background did not differ between groups. Programs with an OPAT pharmacist were more likely to have a formal OPAT team compared to those without an OPAT pharmacist ( < .001). OPAT pharmacists were early in their careers with 66.7% practicing <5 years in OPAT. Most OPAT pharmacists (66.7%) practiced at an academic medical center with a median full-time equivalent (FTE) of 0.6. Moreover, 63% utilized a collaborative practice agreement and 81.5% shared job functions with other pharmacist roles, most commonly antimicrobial stewardship. Few OPAT programs involved a dispensing component (28%). The median daily census was 43 patients followed by an OPAT pharmacist. Pharmacists performed a variety of tasks in OPAT. Pharmacist nondispensing involvement in OPAT is an emerging trend in the United States with wide variability in program structure and pharmacist tasks. A ratio of 1 OPAT pharmacist for every 45-70 OPAT patients is proposed to facilitate expansion of pharmacist clinical practice in OPAT.

Background It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T‐cell (CAR‐T) recipients present with a constellation of signs and symptoms that may represent both complications. Objective The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR‐T recipients. Study design This single‐center, retrospective, medical record review evaluated patients prescribed CAR‐T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR‐T toxicity rates, and broad‐spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC). Results The 98 included patients were a median age of 63 (IQR: 55–69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02–7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48–0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad‐spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075). Conclusion Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR‐T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR‐T therapy. A serum procalcitonin concentration >0.4 ng/mL was significantly associated with confirmed bacterial infection in patients after receiving chimeric antigen T‐cell therapy. Procalcitonin may be a useful marker for differentiating bacterial infection from cytokine release syndrome in chimeric antigen T‐cell therapy recipients.

To assess the safety of a single dose of parenteral ketorolac for analgesia management in geriatric emergency department (ED) patients. This was a retrospective study of all administrations of parenteral ketorolac to adults ≥65 years of age and matched controls. The primary outcome was the occurrence of any of the following adverse events within 30 days of the ED visit: gastrointestinal bleeding, intracranial bleeding, acute decompensated heart failure, acute coronary syndrome, dialysis, transfusion, and death. The secondary outcome was the occurrence of an increase in serum creatinine of ≥1.5 times baseline within 7 and 30 days of the ED visit. There were 480 patients included in the final analysis, of which 120 received ketorolac (3: 1 matching). The primary outcome occurred in 14 of 360 patients who did not receive ketorolac and 2 of 120 ketorolac patients (3.9% vs 1.7%, p = 0.38; OR 2.39, 95% CI 0.54–10.66). There was no occurrence of dialysis or death in either group. The secondary outcome occurred in 1 of 13 and 1 of 23 ketorolac patients with both a baseline serum creatinine and a measure within 7 and 30 days, respectively, but did not occur in patients who did not receive ketorolac (7 days: 7.7% vs 0.0%, p = 0.29; 30 days: 4.4% vs 0.0%, p = 0.22). The use of single doses of parenteral ketorolac for analgesia management was not associated with an increased incidence of adverse cardiovascular, gastrointestinal, or renal adverse outcomes in a select group of older adults.

The optimal antithrombotic therapy following combined coronary artery bypass graft (CABG) and surgical valve replacement (SVR) surgery remains unclear. The aim of this single-center, retrospective cohort study was to assess the safety and effectiveness of a vitamin K antagonist (VKA) plus either aspirin or clopidogrel in patients following combined CABG and SVR. The primary endpoint was the occurrence of bleeding within six months. The secondary endpoint was the occurrence of CV death, stroke, acute coronary syndrome (ACS), or valve dysfunction. Outcomes were identified by pre-specified ICD codes. A total of 629 patients were included in the analysis, with 583 patients receiving aspirin and 46 patients receiving clopidogrel. Bleeding occurred in 1.7% of patients receiving aspirin and in 0% of patients receiving clopidogrel (p  =  0.99). CV death, stroke, ACS, or valve dysfunction occurred in 3.1% of patients receiving aspirin and 4.3% of patients receiving clopidogrel (p  =  0.65). In this study, there were no differences in the safety or effectiveness of a VKA plus either aspirin or clopidogrel following combined CABG and SVR.