The Prevalence of Drug-Drug Interactions with Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Patients in the Intensive Care Unit.

Background: Persons living with human immunodeficiency virus (HIV) (PWH) on antiretroviral therapy (ART) are frequently admitted to the intensive care unit (ICU). Persons living with HIV on ART may be at higher risk for potential drug-drug interactions (pDDIs) due to polypharmacy in the ICU. We determined the prevalence of pDDI with ART in critically ill PWH. Objectives: The primary outcome was prevalence of pDDI between ART and ICU medications. Secondary outcomes included pDDI per ICU admission, pDDI severity, ICU, and hospital length of stay (LOS). Methods: A single-center, retrospective cohort evaluating PWH ≥ 18 years old admitted to the ICU for > 24 hours who received ART during ICU admission, between January 2013 and 2015 at a tertiary care hospital in the United States. Each ICU admission was counted as a separate encounter. Medication databases and chart review were used to identify pDDI. Results: We included 77 PWH encounters; mean age was 55 ± 9 years and 65% were male. We identified 208 pDDIs among 53/77 (68.8%), with a mean 4 ± 2 pDDI per ICU admission. Antipsychotics (20%), analgesics (20%), and anti-lipemics (11%) were the most common ICU medications with ART-related pDDI. Of the pDDI, 64% were major, 24% moderate, and 12% contraindicated. Median ICU and hospital LOS were 4 days (IQR: 3-5) and 11 days (IQR: 7-31), respectively. Conclusion: Most PWH had at least one pDDI during ICU admission. Collaborations among pharmacists, intensivists, and infectious disease/HIV specialists to develop effective, actionable strategies, such as electronic health record alerts, could reduce pDDIs for PWH on ART in the ICU.

Opioid Prescribing at Discharge in Opioid-Naïve Trauma Patients.

BACKGROUND: Opioid analgesics remain mainstay of treatment for trauma-related pain despite growing concerns for opioid dependency or misuse. The purpose of this study was to evaluate opioid prescribing at hospital discharge after traumatic injury. METHODS: This is a single-center, retrospective analysis of patients ≥18 years of age admitted for ≥24 hours with a primary diagnosis of traumatic injury. Those with alcohol use disorder, polysubstance abuse, chronic opioid use, or in-hospital mortality were excluded. The primary outcome was the incidence of patients prescribed opioids at discharge. Secondary outcomes included percent of patients who received nonopioids, intensive care unit (ICU) admission, and hospital length of stay (LOS). RESULTS: Of the 927 encounters, 471 were included. The mean age was 60 ± 23 years, and 62.0% were male. The majority were blunt trauma, and 49.9% were falls. Mean initial injury severity score (ISS) was 9 ± 7.2. Of the 70.4% of patients prescribed opioids, 39.4% were discharged on opioids. Age ≥30 years, ICU admission, ISS <9, or Charlson Comorbidity Index >1 was less likely to have opioids prescribed at discharge. Most received nonopioids (93.6%) and multimodal analgesia (84.3%). The median hospital and ICU LOS were 5 (3-9) and 2 (0-4) days, respectively. DISCUSSION: Only 39.4% had opioids prescribed at discharge. Opioid-reductive strategies may decrease in-hospital and discharge opioid prescribing. While opioid analgesics remain a mainstay of trauma-associated pain management, institution-wide opioid-sparing strategies can further reduce discharge opioid prescribing after trauma.

Evaluation of levetiracetam for early post-traumatic seizure prophylaxis: A level II trauma center experience.

INTRODUCTION: Traumatic brain injury (TBI) can induce early or late post-traumatic seizures (PTS). While PTS incidence is low, prophylaxis is used despite a lack of consensus on agent or duration. Levetiracetam (LEV) for early PTS prophylaxis is preferred due to its safety and efficacy. The purpose of this study was to evaluate LEV for early PTS prophylaxis. METHODS AND MATERIALS: A single-center, retrospective chart review of TBI patients ≥18 years who received LEV for early PTS prophylaxis between August 2018-July 2019. The primary outcome was LEV duration. Secondary outcomes were incidence of seizure, intensive care unit (ICU) and hospital length of stay (LOS). RESULTS: Of the 137 included, mean age was 59 ± 20 years and 69.3% were male. The mean admission GCS was 13 ± 4 and 77.4% had mild TBI. Median LEV duration was 7 (IQR 4-10) days and 13.9% met recommended 7-day duration. Those prescribed LEV >7 days had more than twice the median LEV duration than those prescribed ≤7 days [10.25 (8.5-15.5) vs 4 (1.5-4.5) days, p < 0.0001]. Electroencephalography-confirmed PTS occurred in 2.2%, with an early PTS incidence of 0.73%. Median ICU and hospital LOS were 2 (IQR 1-7) and 7 (IQR 3-16) days, respectively. CONCLUSIONS: The incidence of PTS was low as most patients in our study had mild or moderate TBI. Early PTS prophylaxis with LEV for 7 days is appropriate, although the majority of patients did not meet the recommended duration. Efforts to standardize and implement PTS prophylaxis protocols are needed.

Septic shock due to candida and disseminated herpes simplex virus-1 (HSV1) after elective spinal surgery in an immunocompromised patient with chronic HSV1 infection.

Herpes simplex virus is an infection that can result in a variety of symptoms ranging from blistering or ulcers to severe, systemic manifestations. We report a case of patient who underwent elective spinal surgery and developed invasive herpes as well as candidiasis postoperatively without any direct evidence of immunosuppression.

Impact of Low-Dose Fluconazole on Tacrolimus Dosing in Renal Transplant.

BACKGROUND: The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use. OBJECTIVE: This study quantified the drug interaction between low-dose fluconazole (LDF) and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients. METHODS: We conducted a single-center retrospective chart review of renal transplant patients >18 years who received LDF or nystatin (NYS), and TAC. The primary outcome was the difference in tacrolimus total daily dose (TAC TDD) for LDF versus NYS groups. Secondary outcomes included days with supratherapeutic, therapeutic and subtherapeutic tacrolimus levels, time to therapeutic level, incidence of adverse drug reactions and graft rejection. RESULTS: We evaluated 94 patients and included 81. Low-dose fluconazole received a greater TAC TDD prior to post-operative day (POD) 10 (10.5 ± 4.7 mg vs. 7.1 ± 4.5 mg, p < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 ± 2.2 mg vs. 9.8 ± 0.8 mg, p < 0.001) and following LDF discontinuation (6.9 ± 0.1 mg vs. 9.0 ± 0.4 mg, p < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 ± 7.0 vs. 13.9 ± 8.5; p = 0.02) but fewer with subtherapeutic (6.7 ± 5.7 vs. 12.9 ± 7.2; p < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 ± 5.8 vs. 14.4 ± 6.6, p = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 ± 2.7 vs. 11.5 ± 7.7; p < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection. CONCLUSION: A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels.

Evaluation of Serum Sodium Correction Rates for Management of Hyponatremia in Hospitalized Patients.

BACKGROUND: Appropriate correction of hyponatremia can reduce complications such as osmotic demyelination syndrome (ODS). OBJECTIVE: To evaluate rates of serum sodium correction in hyponatremic hospitalized patients and identify factors associated with higher rates of overcorrection. METHODS: This is an institutional review board-approved single-center, retrospective chart review of patients ≥18 years of age with at least 1 serum sodium <130 mEq/L during hospitalization. The primary end point was percentage of patients appropriately corrected for hyponatremia. Appropriate correction was defined as a sodium change ≤12 mEq/L over 24 hours and 18 mEq/L over 48 hours, and overcorrection was defined as an increase in serum sodium exceeding these cutoffs. Secondary end points included incidence of ODS, poor neurological outcome, intensive care unit (ICU) and hospital lengths of stay (LOSs), and in-hospital mortality. RESULTS: Of 234 patients evaluated, 100 were included. Mean age was 72 ± 16 years, and 47% were male. Overcorrection occurred in 14 patients. There was no incidence of ODS. Rates of poor neurological outcome (P = 0.77), ICU (P = 0.09) and hospital LOS (P = 0.13), and in-hospital mortality (P = 0.20) were similar between appropriately corrected and overcorrected patients. Using a logistic regression analysis, severe hyponatremia (serum sodium < 120 mEq/L; P = 0.0122) and history of alcohol use disorder (P < 0.001) were risk factors found to be associated with overcorrection. CONCLUSION AND RELEVANCE: Overcorrection of hyponatremia occurred in 14% of patients in this study. To minimize this risk, further caution should be taken when managing patients presenting with identified risk factors.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Implementation and evaluation of a virtual learning advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 restricted student involvement in direct patient care. Virtual learning is an effective education strategy in pharmacy curriculums. This study aimed to evaluate student perceptions of virtual learning advanced pharmacy practice experiences (APPE) utilizing an electronic 12-question survey. EDUCATIONAL ACTIVITY AND SETTING: Virtual learning was developed and implemented, and students were surveyed at the end of the APPE. The survey was comprised of one open-ended and 11 Likert scale questions. It assessed implementation and use of virtual learning in place of a standard on-site APPE. FINDINGS: Responses were attained from 19 students. Questions regarding resources provided and virtual learning enabling autonomous, independent learning had the highest percent of strong agreement. No responses indicated strong disagreement. Three questions solicited >10% response rate of somewhat disagree, 16% associated with virtual learning helping the student become a better member of the healthcare team after graduation. Open-ended responses acknowledged appreciation of the virtual APPE and presented material. One in six students commented on the ability to apply the learned information to direct patient care. Feedback was delivered on consideration for increased utility of patient care-orientated applications to facilitate simulation of real-life patient cases. SUMMARY: Students who completed the virtual APPE were satisfied overall. Virtual teaching modalities may be incorporated into APPEs, particularly when direct patient care access is limited, but should not be used to completely replace the experience gained during direct patient care.

Valproic Acid-Induced Thrombocytopenia-Related Spontaneous Systemic Bleeding.

BACKGROUND Valproic acid is utilized for the management of various disease states, but coagulation changes, such as thrombocytopenia, can limit use. Valproic acid is a highly protein-bound drug. Serum levels of 50-100 mcg/mL are considered therapeutic, with minimal risk of toxicity when maintained within the recommended therapeutic index. We present a case of valproic acid-induced thrombocytopenia associated with spontaneous systemic bleeding. CASE REPORT A 57-year-old woman with history of generalized anxiety disorder and choreiform movements presented to the Emergency Department with 1 day of oral and vaginal bleeding. The patient had been started on valproic acid for choreiform movements 3 weeks prior. On physical exam, the patient was noted to have atraumatic contusions and ecchymosis. A CT head revealed left temporal frontal subdural hematoma (4.5 mm), acute subdural hematoma along the posterior aspect of the interhemispheric falx (5 mm), mass effect on the right lateral ventricle, and an approximately 3 mm right-to-left midline shift. Laboratory testing was notable for platelets 4000/µL, hemoglobin 7.3 g/dL, hematocrit 23.1%, fibrinogen 467 mg/dL, and valproic acid random level 26.3 µg/mL. Thromboelastography releveled normal values except for a decreased maximum amplitude of 33.4 mm. CONCLUSIONS Although the clinical relevance is still debated, few case reports of significant bleeding related to valproic acid-induced thrombocytopenia exist. To the best of our knowledge, this is the first case report of spontaneous systemic bleeding due to valproic acid-induced thrombocytopenia in the setting of normal fibrinogen levels. Furthermore, this report demonstrates the potential risk of thrombocytopenia with subtherapeutic VPA levels.

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.