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.

Pharmacist Involvement in Sepsis Response and Time to Antibiotics: A Systematic Review.

Introduction: Sepsis is a life-threatening medical emergency and a leading cause of morbidity and mortality worldwide. Reductions in time to antibiotics in patients presenting with sepsis or septic shock are associated with reduced mortality, and Surviving Sepsis Campaign guidelines recommend antibiotics within one hour of recognition. Pharmacists are well-equipped to help navigate the therapeutic and operational challenges associated with achieving this goal. Objectives: To assess the association of pharmacist involvement in sepsis response with time to antibiotics in hospitalized patients with sepsis and septic shock. Methods: A systematic review of the following databases was conducted: PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Studies must have included a designated role of an individual pharmacist in the management of sepsis or septic shock and not be considered an operational change. The primary outcome of interest was time to antibiotic administration, with secondary outcomes including intensive care unit (ICU) and hospital length of stay as well as in-hospital mortality. Results: We identified 10 studies including 1772 patients with sepsis or septic shock that evaluated a sepsis response in which a pharmacist was included. Studies included patients in the ICU, emergency department, and hospital ward setting. Seven studies demonstrated a significant reduction in time to antibiotics, with two other studies supporting this conclusion in extrapolation or sensitivity analysis. There was not a consistent reduction in ICU or hospital length of stay nor in-hospital mortality between those interventions involving a pharmacist compared with their defined control groups. Conclusion: Pharmacist involvement in sepsis response, often as part of a multi-professional team-based approach to sepsis care, is associated with a reduced time to antibiotic administration for hospitalized patients with sepsis or septic shock.

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.

Artificial intelligence to evaluate postoperative pain based on facial expression recognition.

BACKGROUND: Pain intensity evaluation by self-report is difficult and biased in non-communicating people, which may contribute to inappropriate pain management. The use of artificial intelligence (AI) to evaluate pain intensity based on automated facial expression analysis has not been evaluated in clinical conditions. METHODS: We trained and externally validated a deep-learning system (ResNet-18 convolutional neural network) to identify and classify 2810 facial expressions of 1189 patients, captured before and after surgery, according to their self-reported pain intensity using numeric rating scale (NRS, 0-10). AI performances were evaluated by accuracy (concordance between AI prediction and patient-reported pain intensity), sensitivity and specificity to diagnose pain ≥4/10 and ≥7/10. We then confronted AI performances with those of 33 nurses to evaluate pain intensity from facial expression in the same situation. RESULTS: In the external testing set (120 face images), the deep learning system was able to predict exactly the pain intensity among the 11 possible scores (0-10) in 53% of the cases with a mean error of 2.4 points. Its sensitivities to detect pain ≥4/10 and ≥7/10 were 89.7% and 77.5%, respectively. Nurses estimated the right NRS pain intensity with a mean accuracy of 14.9% and identified pain ≥4/10 and ≥7/10 with sensitivities of 44.9% and 17.0%. CONCLUSIONS: Subject to further improvement of AI performances through further training, these results suggest that AI using facial expression analysis could be used to assist physicians to evaluate pain and detect severe pain, especially in people not able to report appropriately their pain by themselves. SIGNIFICANCE: These original findings represent a major step in the development of a fully automated, rapid, standardized and objective method based on facial expression analysis to measure pain and detect severe pain.

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.

Impact of protocolized diuresis for de-resuscitation in the intensive care unit.

OBJECTIVE: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill. METHODS: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria. RESULTS: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated. CONCLUSIONS: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study.

OBJECTIVES: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients. DESIGN: Prospective, open-label, sequential period pilot study. SETTING: Medical ICU of a large academic medical center. PATIENTS: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded. INTERVENTIONS: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months. MEASUREMENTS AND MAIN RESULTS: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed. CONCLUSIONS: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

Impact of Pharmacist Intervention on Selection and Timing of Appropriate Antimicrobial Therapy in Septic Shock.

BACKGROUND: Current guidelines for septic shock management recommend administration of appropriate, broad-spectrum antimicrobials within 1 hour of recognition. OBJECTIVE: To evaluate the interventions pharmacists make as part of a sepsis response team and to determine if these interventions increase the proportion of patients with appropriate empiric antimicrobial therapy. METHODS: A retrospective cohort study was undertaken reviewing adult patients in a large, academic medical center with confirmed septic shock who had an order for a "sepsis bundle," which includes notification of a pharmacist to assess adequacy of empiric therapy. Pharmacist interventions with regard to selection of empiric antimicrobials were documented. The proportion of patients with initial successful selection of antimicrobial therapy (SSAT) before and after pharmacist intervention was assessed as well as the time to first antimicrobial administration and time to appropriate antimicrobial administration. RESULTS: A total of 76 patients were included. Pharmacist intervention increased the proportion of patients with SSAT from 66% to 80% ( P = .04). Median time to first antimicrobial administration was 43 minutes, and time to appropriate antimicrobial therapy was 1 hour, 34 minutes for the entire cohort, with pharmacist intervention decreasing the latter time significantly in patients without SSAT on initiation of the "sepsis bundle" ( P < .001). CONCLUSION: Pharmacist assessment of patients in septic shock offers the opportunity to improve SSAT. Systems designed to use a pharmacist responder for the care of patients with septic shock maximize the selection of antimicrobials, facilitate rapid administration, and improve surrogate outcomes for mortality in septic shock.

Managing the Rising Costs and High Drug Expenditures in Critical Care Pharmacy Practice.

Pharmaceutical costs for patients in the intensive care unit (ICU) constitute a large portion of hospital drug budgets. Unfortunately, prices for medications commonly used in the ICU are on the rise for a variety of reasons. In particular, the U.S. Food and Drug Administration's Unapproved Drugs Initiative, generic manufacturers cornering the marketplace, drug shortages, and regulatory device changes are major drivers of pharmaceutical price escalation affecting costs in the ICU. Furthermore, traditional high acquisition cost items still pose challenges to controlling costs. To offer strategies to mitigate the rising costs of pharmaceuticals in the ICU setting, we searched the PubMed/Medline and International Pharmaceutical Abstracts databases and other related sources to identify published cost-saving protocols concerning specific medications that are affected by rising prices or have traditional high acquisition costs. In the absence of specific protocols, we offer possible cost-saving initiatives based on published literature regarding specific agents or based on our own diverse set of experiences. Finally, we review suggested clinical and operational activities at an institutional level to address these rising drug costs in the ICU setting.