Evaluation of an Association Between Enoxaparin Dose per Estimated Blood Volume and Clinically Relevant Bleeding in Low-Weight Trauma Patients.

BACKGROUND: The optimal dosing for enoxaparin venous thromboembolism (VTE) prophylaxis in low-weight trauma patients is unknown. Estimated blood volume (EBV) has shown promise as a dose modifier. OBJECTIVE: To characterize the association of enoxaparin dose per EBV with the prevalence of VTE and bleeding in low-weight trauma patients. METHODS: This was a retrospective study of trauma patients admitted over a 4-year period. Included patients were adults weighing <60 kg who received a minimum of 3 consecutive doses of enoxaparin. The primary endpoint was a comparison of enoxaparin dose per EBV in patients experiencing bleeding and VTE. Secondary endpoints included comparisons of dose per body mass index (BMI) and total body weight (TBW) and the ability of dose per EBV to predict clinical endpoints. Subgroup analyses for patients weighing <50 kg were performed for all endpoints. RESULTS: A total of 189 patients were included. Statistical comparisons for VTE were not performed because of low prevalence. The dose of enoxaparin per EBV was not statistically different between patients who did and did not bleed in all analyses. Doses per BMI and TBW were also not statistically different between the groups. In patients weighing <50 kg, numerically higher doses per EBV, BMI, and TBW were noted in patients that bled versus those that did not. Enoxaparin dose per EBV was not a statistically significant predictor of bleeding in logistic regression models. CONCLUSION AND RELEVANCE: No significant associations between enoxaparin dose per EBV, BMI, or TBW and bleeding were noted in the study. Future analyses of EBV and other dose modifiers should consider inclusion of patients weighing <50 kg.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Effectiveness of Body Mass Index-Based Prophylactic Enoxaparin Dosing in Bariatric Surgery Patients.

INTRODUCTION: Enoxaparin is administered for venous thromboembolic (VTE) prophylaxis in bariatric surgery patients. There is concern whether body mass index (BMI)-based enoxaparin dosing consistently achieves prophylactic targets in patients with severe obesity. METHODS: This retrospective study included patients who underwent bariatric surgery at an academic medical center from Jan 2015-May 2021 and had an anti-Xa level drawn 2.5-6 h after ≥3 doses of BMI-based prophylactic enoxaparin. The primary outcome was the percentage of patients who achieved a target anti-Xa level. Secondary outcomes were prevalence of venous thromboembolic and bleeding events within 30 d post-operatively. RESULTS: Overall, 137 patients were included. Mean BMI was 59.1 ± 10.4 kg/m2, mean age was 43.9 ± 13.3 y and 110 patients (80.3%) were female. Target anti-Xa levels were achieved in 116 patients (84.7%); 14 (10.2%) were above target and 7 (5.1%) were below target. Patients with above target anti-Xa levels were significantly shorter in height than those within target range (167.1 versus 159.8 cm, P = 0.003). Five patients (3.6%) had a bleeding event; no thromboembolisms occurred. Anti-Xa levels correlated more strongly with enoxaparin dose per unit estimated blood volume (EBV) than dose per unit BMI (Rho = 0.54 versus Rho = 0.33). CONCLUSIONS: Target range anti-Xa levels were achieved in 85% of patients using BMI-based enoxaparin dosing. Patients with above target anti-Xa levels were significantly shorter by nearly 3 inches, suggesting an increased risk of overdosing enoxaparin in shorter, obese patients. An EBV-based dosing regimen may better account for patient height and is supported by a greater correlation with anti-Xa levels with dosing based on EBV than BMI.

Inpatient Perioperative Formulary Restriction of Intravenous Acetaminophen at Vizient Partner Hospitals: A National Survey of Pharmacists.

Purpose: Despite potential benefits of intravenous (i.v.) administration of acetaminophen (APAP), consistent outcome data are lacking. This, combined with the higher acquisition cost of the drug, has led to variation in i.v. APAP management strategies. This project evaluated the contemporary formulary status and restrictions of i.v. APAP in the perioperative setting. Methods: A survey focusing on i.v. APAP formulary restriction in the perioperative setting was developed by the Vizient Pharmacy Research Committee and distributed to Vizient Pharmacy Program participant listservs for Pharmacy Directors or Drug Information Pharmacists. The four survey domains included hospital characteristics, perioperative i.v. APAP formulary status and prescribing restrictions, perioperative i.v. APAP use, and perioperative i.v. APAP medication use evaluation (MUE) results. Responses were collected and summarized, and primary outcomes were evaluated using Fisher's exact test. Results: A total of 1195 surveys were distributed with a response rate of 19%. Respondents were equally distributed between academic medical centers (AMC) and non-academic medical centers (non-AMC). Two cohorts were examined: those with i.v. APAP on formulary and those without. The non-AMCs showed a larger proportion of hospitals with the medication on formulary (P = .041). Regarding formulary decision-making, the AMCs were more considerate of value. Several different practices were employed to limit or restrict i.v. APAP. Conclusion: A survey of directors of pharmacy and drug information specialists revealed that the majority of hospitals have i.v. APAP on formulary for perioperative use, but use is restricted. Differences in i.v. APAP formulary practices between AMCs and non-AMCs warrant further consideration.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN: The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING: The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS: We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS: Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Antibiotic Duration and Outcome Complications for Surgical Site Infection Prevention in Traumatic Mandible Fracture.

BACKGROUND: The appropriate duration of antibiotic therapy for surgical site infection (SSI) prevention in traumatic mandibular fracture repair is unknown, and practices vary significantly. The objective of this study was to characterize antibiotic duration and outcomes after surgical repair of traumatic mandibular fracture. METHODS: A single-center, retrospective analysis of all adult patients who underwent surgical fixation of a mandible fracture between January 2014 and December 2016 was performed. Operative service was categorized between otolaryngology (ear, nose, and throat surgery), plastic and reconstructive surgery, and oral and maxillofacial services. Primary outcomes were SSI and operative complications (including osteomyelitis, nonunion, malocclusion, and hardware infections). Differences in antibiotic prescription pattern were analyzed using analysis of variance test and Pearson chi-squared test. RESULTS: A total of 75 patients were included in the study with 33 (44.0%), 26 (34.7%), and 16 (21.3%) managed by plastic and reconstructive surgery, ear, nose, and throat surgery, and oral and maxillofacial services, respectively. Median age was 30.0 y. Median injury severity score was 4.0. There was no significant difference in hospital length of stay (P = 0.44), intensive care unit length of stay (P = 0.53), or postoperative complications (P = 0.15). None of our patients developed an SSI or postantibiotics complications. Although the total inpatient duration of antibiotics was not significantly different among services (P = 0.37), there were significant differences in outpatient duration of antibiotics (P = 0.007) and total duration of antibiotics (P = 0.003). CONCLUSIONS: Duration of antibiotics is not associated with postoperative SSI or antibiotics-related complications. The wide variation in prescribing practices and lack of any clear benefit for prolonged antibiotics provides an opportunity to explore the benefits of a standardized short course of antibiotics. LEVEL OF EVIDENCE: Therapeutic study, III.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Implementation of Polymerase Chain Reaction to Rule Out Clostridium difficile Infection Is Associated With Reduced Empiric Antibiotic Duration of Therapy.

PURPOSE: The polymerase chain reaction (PCR) test has higher sensitivity and a faster turnaround time than the enzyme immunoassay (EIA) for identification of Clostridium difficile, although the clinical implications of these variables are not well described. METHODS: Inpatients with a negative EIA (n = 79) or PCR (n = 87) test were retrospectively evaluated. Patients were excluded if they had a positive EIA or PCR test during the same hospitalization or if they were currently receiving treatment for C. difficile infection (CDI) prior to admission. The primary outcome was empiric CDI antibiotic duration of therapy associated with each test method. RESULTS: Empiric CDI antibiotic duration of therapy was 2.31 (95% confidence interval [CI], 1.48-3.15) days for the EIA group and 0.88 (0.45-1.33) days for the PCR group (P = .007). Number of diagnostic laboratory tests performed per patient were 2.73 (2.64-2.83) and 1.16 (1.04-1.28) tests, respectively (P < .001). CONCLUSION: Use of the PCR test to rule out CDI was associated with reduced duration of empiric CDI antibiotic therapy and fewer diagnostic laboratory tests performed per patient. When combined with fewer diagnostic laboratory tests performed per patient and shorter duration of contact isolation, the higher acquisition cost of the PCR test was offset, resulting in cost neutrality. These findings provide additional data to support the routine use of the PCR test.

Multicenter study evaluating target attainment of anti-Factor Xa levels using various enoxaparin prophylactic dosing practices in adult trauma patients.

STUDY OBJECTIVE: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients. DESIGN: Multicenter, retrospective review. DATA SOURCE: Electronic health records from participating institutions. PATIENTS: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement. INTERVENTION: Dosing strategy used to determine initial prophylactic dose of enoxaparin. MEASUREMENTS: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL). MAIN RESULTS: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant. CONCLUSIONS: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients.

Phenytoin removal by continuous venovenous hemofiltration.

OBJECTIVE: To describe 2 cases of clinically significant phenytoin removal during continuous venovenous hemofiltration (CVVH) and review the relevant literature regarding phenytoin removal by renal replacement modalities. CASE SUMMARY: A 64-year-old female with chronic kidney disease and cirrhosis was admitted to the intensive care unit (ICU) with a traumatic subdural hematoma and seizures. The patient received a loading dose of intravenous phenytoin 1000 mg, followed by maintenance intravenous administration of phenytoin 100 mg and levetiracetam 250 mg every 12 hours. CVVH was initiated for acidosis. A 63-year-old male was admitted to the ICU after cardiac surgery complicated by hypotension. CVVH was initiated for fluid overload, and phenytoin was initiated 3 days later for seizures. A loading dose of intravenous phenytoin 2700 mg was administered, followed by maintenance dosing of intravenous phenytoin 150 mg every 8 hours. Concentrations of unbound phenytoin in serum and CVVH effluent samples were measured during concomitant treatment in each patient. In both patients, serum and effluent concentrations of unbound phenytoin fell steadily while they were on CVVH. Clearance of phenytoin by CVVH was calculated, as was the daily removal of phenytoin, as a percentage of total daily phenytoin dosage during each sampling period. Phenytoin clearance by CVVH ranged from 11 to 13 mL/min in these patients. DISCUSSION: The clearance of phenytoin with CVVH in these 2 patients was much higher than the renal clearance of phenytoin reported in healthy volunteers with normal renal function. Previous case reports have demonstrated that only small, clinically insignificant amounts of phenytoin are removed by hemodialysis, and the only published report of phenytoin removal by continuous renal replacement therapy used hemofiltration rates much lower than those used in the 2 cases described here. CONCLUSIONS: These cases demonstrate that a substantial amount-approximately 30%-of total daily phenytoin dose may be removed by CVVH, and patients may require higher than expected empiric doses. Phenytoin concentrations should be closely monitored in critically ill patients receiving CVVH.

Optimizing discharge opioid prescribing in trauma patients: A quasi-experimental study.

BACKGROUND: Patients prescribed higher opioid dosages are at increased risk of overdose and death without added pain reduction. Increases in opioid prescribing continue to fuel the epidemic. We hypothesized a comprehensive guideline to standardize opioid prescribing would decrease postdischarge dosages for patients experiencing trauma without requiring additional refills. METHODS: This quasiexperimental study compared opioid prescribing by trauma providers before and after the implementation of a departmental guideline on April 1, 2019, aimed at aligning opioid prescription patterns with Centers for Disease Control and Prevention recommendations. Patients prescribed opioids before implementation were the control group, whereas patients prescribed opioids after were the intervention group. The primary outcome was the proportion of patients receiving ≥50 morphine milligram equivalents per day. RESULTS: We identified 293 and 280 patients experiencing trauma in the control and intervention groups, respectively. There were no differences between the groups' Injury Severity Score (P = .69) or the frequency of having a procedure performed (P = .80). Total morphine milligram equivalents and maximum morphine milligram equivalents per day were 16% and 25% lower, respectively, in the intervention group compared with the control group (P < .001). The proportion of trauma patients prescribed ≥50 morphine milligram equivalents per day at discharge decreased from 57% to 18% after implementation (P < .001). The proportion of trauma patients prescribed ≥90 morphine milligram equivalents per day also decreased, from 37% to 14% (P < .001). There was no significant increase in the frequency of refill requests (P = .105) or refill prescriptions (P = .099) after discharge. CONCLUSION: A departmental guideline aimed at optimizing opioid prescription patterns successfully lowers the amount of morphine milligram equivalents prescribed to trauma patients and improves compliance with Centers for Disease Control and Prevention recommendations.

Evaluation of a novel blood volume-based enoxaparin dosing guideline for venous thromboembolism prophylaxis in trauma patients.

PURPOSE: Fixed-dose and body mass index (BMI)-based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)-based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients. METHODS: This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti-factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL). RESULTS: A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups. CONCLUSION: Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels.

Prospective Observational Evaluation of Predatory Journals in Critical Care Pharmacy Practice: Defining Characteristics Associated With Receiving Unsolicited Invitations to Publish.

Open-access publishing promotes accessibility to scholarly research at no cost to the reader. The emergence of predatory publishers, which exploit the author-pay model by charging substantial publication fees for publication in journals with questionable publishing processes, is on the rise. Authors are solicited through aggressive marketing tactics, though who is targeted is not well described. The purpose of this study was to identify characteristics associated with critical care pharmacists that make them targets of unsolicited invitations to publish. A prospective, observational study of critical care pharmacists was performed. Participants archived emails received by their professional email that were unsolicited invitations to submit their original work for publication in a journal (unsolicited journals). Variables were evaluated to determine which were associated with unsolicited invitations; these were compared to legitimate journals, defined as all PubMed-indexed journals in which the participants were previously published. Twenty-three pharmacist participants were included, all of whom were residency and/or fellowship trained and practicing in an academic medical center. Participants had a median of 7 years of experience since their post-graduate training, 6 years since their last change in professional email address, and 2 years since their first PubMed-indexed publication. From these participants, 136 unsolicited and 59 legitimate journals were included. The average number of invitations increased 1.04 (95% CI, 1.02-1.05) times for every additional PubMed-indexed publication (P < .001). Most unsolicited journals were considered predatory. Legitimate and unsolicited journals differed significantly. The number of previous PubMed-indexed publications strongly correlates with the likelihood of critical care pharmacists receiving unsolicited publication invitations, often from predatory journal.

Evaluation of anti-factor Xa concentrations using a body mass index-based enoxaparin dosing protocol for venous thromboembolism prophylaxis in trauma patients.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a body mass index (BMI)-based enoxaparin prophylaxis dosing protocol at achieving target anti-factor Xa (anti-Xa) concentrations in the trauma population. METHODS: This retrospective chart review evaluated anti-Xa concentrations in adult trauma patients who received prophylactic enoxaparin over a three-month period. The primary outcome was the percentage of patients that achieved target anti-Xa concentrations after ≥3 doses of enoxaparin. Secondary outcomes included correlations of anti-Xa concentrations with enoxaparin dose per BMI, total body weight (TBW), and estimated blood volume (EBV). The prevalence of clinically relevant bleeding and venous thromboembolism was also recorded. Multivariable logistic regression was used to identify associated variables for target anti-Xa concentration attainment. RESULTS: Ninety-nine consecutive patients were included in the study. Included patients were predominately male (69.7%) and Black (50.5%) with a mean age of 44.1 years. Target anti-Xa concentrations were achieved in 62.6% of patients. Anti-Xa concentrations were moderately correlated with enoxaparin dose per EBV (ρ = 0.57), followed by dose per TBW (ρ = 0.46), and dose per BMI (ρ = 0.20). Multivariable logistic regression demonstrated that categorization of enoxaparin dose per EBV and per TBW were the only statistically significant predictors of reaching target anti-Xa concentrations (p = <0.001). CONCLUSIONS: In adult trauma patients, the rate of achieving target anti-Xa concentrations remains suboptimal and provides room for further improvement. Enoxaparin dose per EBV was more closely correlated with anti-Xa concentrations when compared to TBW and BMI. Dosing per EBV and TBW was the only variables associated with reaching target anti-Xa concentrations within the study. Further investigation is warranted to elucidate optimal EBV- and TBW-based dosing regimens.

Multicenter Retrospective Review of Ketamine Use in the ICU.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study. CONCLUSIONS AND RELEVANCE: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.

PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study.

To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community hospitals and academic medical centers in the United States. PARTICIPANTS: ICU clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions; $5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions; $9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions; $1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was $418 per intervention, $845 per patient day, and $7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between $3.3:1 and $9.6:1. CONCLUSIONS: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between $3.3:1 and $9.6:1.

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study.

To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community and academic hospitals in the United States. PARTICIPANTS: Emergency medicine clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1. CONCLUSIONS: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.