Impact of a Pharmacist-Driven Medication Diluent Volume Optimization Protocol on Fluid Balance and Outcomes in Critically Ill Patients.

Background: Volume overload (VO) is common in the intensive care unit (ICU) and associated with negative outcomes. Approaches have been investigated to curtail VO; however, none specifically focused on medication diluent volume optimization. Objective: Investigate the impact of a pharmacist-driven medication diluent volume optimization protocol on fluid balance in critically ill patients. Methods: A prospective, pilot study was conducted in a medical ICU during October 2021 to December 2021 (pre) and February 2022 to April 2022 (post). A pharmacist-driven medication diluent volume optimization protocol focusing on vasopressor and antimicrobial diluent volumes was implemented. Demographics and clinical data were collected during ICU admission up to 7 days. The primary outcome was net fluid balance on day 3. Secondary outcomes were medication volumes administered, net fluid balance, ICU length of stay, and mortality. Results: Supply chain shortages caused the study to stop at the end of February 2022. Overall, 152 patients were included (123 pre group, 29 post group). The most common admission diagnosis was acute respiratory failure (35%). Vasopressors and antimicrobials were utilized in 47% and 66% of patients, respectively. Net fluid balance on day 3 was greater but not significant in the post group (227.1 mL [-1840.3 to 3483.7] vs 2012.3 mL [-2686.0 to 4846.0]; P = .584). Antimicrobial diluent volumes were significantly less in the post group. No differences were seen in other secondary outcomes. Protocol group assignment was not associated with net fluid balance on day 3. Conclusion: Despite decreasing antimicrobial volume contributions, optimizing diluent volumes alone did not significantly impact overall volume status. Future studies should focus on comprehensive approaches to medication diluent optimization and fluid stewardship.

Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem.

Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.

A Case of an Intraoperative Iatrogenic Methanol Exposure.

BACKGROUND ThinPrep Cytolyt is a methanol-based cell preservation solution frequently used to fix tissue samples immediately following endobronchial ultrasound-guided fine-needle aspiration. Currently, no published reports describe an iatrogenic exposure to Cytolyt. We report the only known case of an accidental intraoperative administration of a methanol solution, with corresponding plasma concentrations, and successful treatment with fomepizole. CASE REPORT A 70-year-old woman with a history of stage IIIA rectal adenocarcinoma was referred for evaluation of a newly identified lung mass. During the procedure, a bronchoalveolar lavage (BAL) of the right upper lobe was performed. After BAL, the proceduralist was informed that the syringe used to instill fluid for the BAL contained Cytolyt rather than saline. The Department of Medical Toxicology was contacted immediately, and the patient received a 15 mg/kg dose of fomepizole. The first plasma methanol level, before fomepizole administration, was elevated to 21 mg/dL. The methanol level was 13 mg/dL 3 h after fomepizole treatment and even lower thereafter; therefore, no additional fomepizole was required. The patient did not develop signs of systemic toxicity and was discharged on hospital day 3. CONCLUSIONS Following methanol exposures, patients can exhibit metabolic acidosis, with potential for blindness, hemodynamic instability, and possibly death if untreated. Fomepizole (4-methylpyrazole) inhibits alcohol dehydrogenase and is a mainstay of treatment. Preventing medical errors is key in ensuring optimal patient care and decreasing adverse events. Providers using CytoLyt and any similar products should be aware of this potential error and approach the possibility of methanol toxicity as they would other routes of methanol exposure.

Niche Roles for Dexmedetomidine in the Intensive Care Unit.

OBJECTIVE: Review dexmedetomidine use in critically ill patients for niche indications including sleep, delirium, alcohol withdrawal, sepsis, and immunomodulation. DATA SOURCES: Literature was sought using PubMed (February 2012-November 2022). Search terms included dexmedetomidine AND (hypnotics OR sedatives OR sleep OR delirium OR immunomodulation OR sepsis OR alcohol withdrawal). STUDY SELECTION AND DATA EXTRACTION: Relevant studies conducted in humans ≥18 years published in English were included. Exclusion criteria included systematic reviews, meta-analyses, and studies evaluating oral dexmedetomidine or other alpha-2 agonists. DATA SYNTHESIS: A total of 231 articles were retrieved. After removal of duplicates, title and abstract screening, and application of inclusion criteria, 35 articles were included. Across the clinical conditions included in this review, varying clinical outcomes were seen. Dexmedetomidine may improve morbidity outcomes in delirium, sleep, and alcohol withdrawal syndrome. Due to limited human studies and poor quality of evidence, no conclusions can be drawn regarding the role of dexmedetomidine in immunomodulation or sepsis. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review presents data for potential niche roles of dexmedetomidine aside from sedation in critically ill patients. This may serve as a guide for sedation selection in critically ill patients who may also benefit from the pleiotropic effects of dexmedetomidine due to a clinical condition discussed in this review. CONCLUSION: While further studies are needed, dexmedetomidine may provide benefit in other indications in critically ill patients including delirium, sleep, and alcohol withdrawal. Given the poor quality of evidence of dexmedetomidine use in immunomodulation and sepsis, no conclusions can be drawn.

Contemporary targeted temperature management: Clinical evidence and controversies.

Advancements in cardiac arrest and post-cardiac arrest care have led to improved survival to hospital discharge. While survival to hospital discharge is an important clinical outcome, neurologic recovery is also a priority. With the advancement of targeted temperature management (TTM), the American Heart Association guidelines for post-cardiac arrest care recommend TTM in patients who remain comatose after return of spontaneous circulation (ROSC). Recently, the TTM2 randomized controlled trial found no significant difference in neurologic function and mortality at 6-months between traditional hypothermia to 33°C versus 37.5°C. While TTM has been evaluated for decades, current literature suggests that the use of TTM to 33° when compared to a protocol of targeted normothermia does not result in improved outcomes. Instead, perhaps active avoidance of fever may be most beneficial. Extracorporeal cardiopulmonary resuscitation and membrane oxygenation can provide a means of both hemodynamic support and TTM after ROSC. This review aims to describe the pathophysiology, physiologic aspects, clinical trial evidence, changes in post-cardiac arrest care, potential risks, as well as controversies of TTM.

Cefepime Induced Neurotoxicity Following A Regimen Dose-Adjusted for Renal Function: Case Report and Review of the Literature.

Introduction: Cefepime induced neurotoxicity (CIN) is commonly associated with renal dysfunction, however CIN can occur in patients with normal renal function or renally dose-adjusted regimens. Few reports of this kind have obtained cefepime concentrations to assist in diagnosis. Patient Case: A 42-year old female with a complex past medical history was transferred to our facility with chief complaint of worsening shock and respiratory failure, and the patient was also noted to be hypernatremic, experiencing diabetic ketoacidosis (DKA), and acute kidney injury (AKI). Her DKA resolved and hypernatremia and AKI began to improve. As a result, cefepime was dose-adjusted for renal function estimated by the Cockcroft-Gault (CG) equation. Her hospital course was complicated by persistent altered mental status (AMS), preventing extubation. Cefepime was discontinued due to concern for CIN, and a concentration was obtained 13-hours after the last dose which was elevated at 49 µg/mL. Two days following cefepime discontinuation, the patient's mental status improved allowing for successful extubation. The patient remained stable and was discharged to an acute care floor and then ultimately back to home. Conclusion: CIN should be part of a wider differential diagnosis for patients experiencing encephalopathy, and inaccurate renal function estimation may be a risk factor for developing CIN. Furthermore, therapeutic drug monitoring (TDM) may serve as an important clinical tool in diagnosing and managing CIN.

Pharmacotherapy in Coronavirus Disease 2019 and Risk of Secondary Infections: A Single-Center Case Series and Narrative Review.

Since the onset of the coronavirus disease 2019 pandemic, immune modulators have been considered front-line candidates for the management of patients presenting with clinical symptoms secondary to severe acute respiratory syndrome coronavirus 2 infection. Although heavy emphasis has been placed on early clinical efficacy, we sought to evaluate the impact of pharmacologic approach to coronavirus disease 2019 within the ICU on secondary infections and clinical outcomes. DATA SOURCES: PubMed (inception to March 2021) database search and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to coronavirus disease 2019, management of severe acute respiratory syndrome coronavirus 2-associated respiratory failure, and prevalence of secondary infections with pharmacotherapies were selected. The MeSH terms "COVID-19," "secondary infection," "SARS-CoV-2," "tocilizumab," and "corticosteroids" were used for article identification. Articles were narratively synthesized for this review. DATA SYNTHESIS: Current data surrounding the use of tocilizumab and/or corticosteroids for coronavirus disease 2019 management are limited given the short follow-up period and conflicting results between studies. Further complicating the understanding of immune modulator role is the lack of definitive understanding of clinical impact of the immune response in coronavirus disease 2019. CONCLUSIONS: Based on the current available literature, we suggest prolonged trials and follow-up intervals for those patients managed with immune modulating agents for the management of coronavirus disease 2019.

The immunomodulatory effects of opioids and implications for intensive care unit populations.

Analgesia within the intensive care unit (ICU) is often achieved via the utilization of opioids in alignment with current guidelines. Recent evidence has not only demonstrated the potential impact of opioids in suppression of immune function, but also the potential harm of immunosuppression of patients within the ICU. Despite the potential immunosuppression seen with opioids in this at-risk population, their use remains frequent. In this review, we highlight the potential immunomodulatory impact of opioids within the critically ill and considerations for their use.

To Block or Not: Updates in Neuromuscular Blockade in Acute Respiratory Distress Syndrome.

Objective: To review and evaluate neuromuscular blocking agents (NMBAs) in critically ill patients with acute respiratory distress syndrome (ARDS). Data Sources: A literature search utilizing PubMed was performed (January 1991 to January 2020) using the following search terms: (neuromuscular blocking agents OR neuromuscular blockade OR cisatracurium OR rocuronium OR vecuronium OR pancuronium OR atracurium) AND *acute respiratory distress syndrome OR acute lung injury). Publications in English were evaluated. Study Selection and Data Extraction: Relevant clinical studies in humans were considered. Data Synthesis: Although NMBAs have been used for decades in the setting of ARDS, questions regarding mortality benefit remain. Early NMBA, within 48 hours of lung injury, have been historically used in critically ill patients with ARDS to aid in increasing alveolar recruitment, improving patient-ventilator synchrony, and promoting oxygenation by the prevention of contraction of respiratory muscles. Until recently, the literature showed an improvement in 90-day adjusted mortality. However, recent literature has demonstrated the lack of a mortality benefit. The continued receipt of NMBAs, with no clear benefit, could potentially lead to increased costs, skin breakdown, corneal abrasions, venous thromboembolisms, intensive care unit acquired weakness, and awareness with inappropriate sedation. Relevance to Patient Care and Clinical Practice: This review aims at discussing the preferred NMBA based on mechanism of action and reviews specific clinical trial data for the use of NMBAs in ARDS, clinical implications of these trial data, complications for the use of NMBAs, and needed future directions. Conclusions: The mortality benefit of NMBAs in ARDS has contradicting evidence with potentially serious adverse effects and notable controversies.

Pathophysiology of Volume Administration in Septic Shock and the Role of the Clinical Pharmacist.

Objective: To review physiological rationale and evidence base surrounding fluid harm to prepare the clinical pharmacist for accountability regarding volume-related outcomes. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (fluid therapy) AND [(critical care) OR (sepsis)] from 1966 to August 2019 published in English. Study Selection and Data Extraction: A total of 3364 citations were reviewed with only relevant clinical data extracted. Data Synthesis: Although early fluid resuscitation may be a necessary component to decrease mortality in the majority of patients with septic shock admitted to the intensive care unit (ICU), the benefit of continued administration after the first 24 hours is uncertain. Paradoxically, a positive fluid balance secondary to intravenous fluid receipt has been associated with diverse and perpetuating detriment on a multitude of organ systems after the first 24 hours of ICU stay. Continued clinical harm has been demonstrated on patient outcomes such as rates of mortality and length of stay. Despite the growing body of evidence supporting the potential adverse aspects of positive fluid balance, fluid overload remains common during critical care admission. Conclusion: Physiological concerns to overly zealous fluid administration and subsequent volume overload are vast. Relevance to Patient Care and Clinical Practice: Optimization of fluid balance in critically ill patients with sepsis is primed for clinical pharmacy intervention. Critical care pharmacists have the potential to improve patient care by optimizing fluid pharmacotherapy while potentially reducing adverse events, days on mechanical ventilation, and length of ICU stay.