The impact of sugammadex dosing and administration practices on potential cost savings for pharmacy departments.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments. SUMMARY: We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices. CONCLUSION: Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings.

Association of systolic, diastolic, mean, and pulse pressure with morbidity and mortality in septic ICU patients: a nationwide observational study.

BACKGROUND: Intensivists target different blood pressure component values to manage intensive care unit (ICU) patients with sepsis. We aimed to evaluate the relationship between individual blood pressure components and organ dysfunction in critically ill septic patients. METHODS: In this retrospective observational study, we evaluated 77,328 septic patients in 364 ICUs in the eICU Research Institute database. Primary exposure was the lowest cumulative value of each component; mean, systolic, diastolic, and pulse pressure, sustained for at least 120 min during ICU stay. Primary outcome was ICU mortality and secondary outcomes were composite outcomes of acute kidney injury or death and myocardial injury or death during ICU stay. Multivariable logistic regression spline and threshold regression adjusting for potential confounders were conducted to evaluate associations between exposures and outcomes. Sensitivity analysis was conducted in 4211 patients with septic shock. RESULTS: Lower values of all blood pressures components were associated with a higher risk of ICU mortality. Estimated change-points for the risk of ICU mortality were 69 mmHg for mean, 100 mmHg for systolic, 60 mmHg for diastolic, and 57 mmHg for pulse pressure. The strength of association between blood pressure components and ICU mortality as determined by slopes of threshold regression were mean (- 0.13), systolic (- 0.11), diastolic (- 0.09), and pulse pressure (- 0.05). Equivalent non-linear associations between blood pressure components and ICU mortality were confirmed in septic shock patients. We observed a similar relationship between blood pressure components and secondary outcomes. CONCLUSION: Blood pressure component association with ICU mortality is the strongest for mean followed by systolic, diastolic, and weakest for pulse pressure. Critical care teams should continue to follow MAP-based resuscitation, though exploratory analysis focusing on blood pressure components in different sepsis phenotypes in critically ill ICU patients is needed.

A Delphi Process to Identify Relevant Outcomes That May Be Associated With a Predictive Analytic Tool to Detect Hemodynamic Deterioration in the Intensive Care Unit.

Background The critical care literature has seen an increase in the development and validation of tools using artificial intelligence for early detection of patient events or disease onset in the intensive care unit (ICU). The hemodynamic stability index (HSI) was found to have an AUC of 0.82 in predicting the need for hemodynamic intervention in the ICU. Future studies using this tool may benefit from targeting those outcomes that are more relevant to clinicians and most achievable. Methods A three-round Delphi study was conducted with a panel of 10 critical care physicians and three nurses in the United States to identify outcomes that may be most relevant and achievable with the HSI when evaluated for use in the ICU. To achieve criteria for relevance, at least 65% of panelists had to rate an outcome as a 4 or 5 on a 5-point scale. Results Nineteen of 24 outcomes that may be associated with the HSI achieved consensus for relevance. The Kemeny-Young approach was used to develop a matrix depicting the distribution of outcomes considering both relevance and achievability. "Reduces time spent in hemodynamic instability" and "reduces times to recognition of hemodynamic instability" were the highest-ranking outcomes considering both relevance and achievability. Conclusion This Delphi study was a feasible method to identify relevant outcomes that may be associated with an appropriate predictive analytic tool in the ICU. These findings can provide insight to researchers looking to study such tools to impact outcomes relevant to critical care practitioners. Future studies should test these tools in the ICU that target the most clinically relevant and achievable outcomes, such as time spent hemodynamically unstable or time until actionable nursing assessment or treatment.

Systematic review and meta-analysis of the correlation between bispectral index (BIS) and clinical sedation scales: Toward defining the role of BIS in critically ill patients.

INTRODUCTION: The bispectral index (BIS) is an attractive approach for monitoring level of consciousness in critically ill patients, particularly during paralysis, when commonly used sedation scales cannot be used. OBJECTIVES: As a first step toward establishing the utility of BIS during paralysis, this review examines the strength of correlation between BIS and clinical sedation scales in a broad population of non-paralyzed, critically ill adults. METHODS: We included studies evaluating the strength of correlation between concurrent assessments of BIS and Richmond Agitation Sedation Scale (RASS), Ramsay Sedation Scale (RSS), or Sedation Agitation Scale (SAS) in critically ill adult patients. Studies involving assessment of depth sedation periperative or procedural time periods, and those reporting BIS and sedation scale assessments conducted >5 min apart or while neuromuscular blocking agents (NMBA) were administered, were excluded. Data were abstracted on sedation scale, correlation coefficients, setting, patient characteristics, and BIS assessment characteristics that could impact the quality of the studies. RESULTS: Twenty-four studies which enrolled 1235 patients met inclusion criteria. The correlation between BIS and RASS, RSS, and SAS overall was 0.68 (95% confidence interval, 0.61-0.74, Ƭ2  = 0.06 I2  = 71.26%). Subgroup analysis by sedation scale indicated that the correlation between BIS and RASS, RSS, and SAS were 0.66 (95% confidence interval 0.58-0.73, Ƭ2  = 0.01 I2  = 30.20%), 0.76 (95% confidence interval 0.69-0.82, Ƭ2  = 0.04 I2  = 67.15%), and 0.53 (95% confidence interval 0.42-0.63, Ƭ2  = 0.01 I2  = 26.59%), respectively. Factors associated with significant heterogeneity included comparator clinical sedation scale, neurologic injury, and the type of intensive care unit (ICU) population. CONCLUSIONS: BIS demonstrated moderate to strong correlation with clinical sedation scales in adult ICU patients, providing preliminary evidence for the validity of BIS as a measure of sedation intensity when clinical scales cannot be used. Future studies should determine whether BIS monitoring is safe and effective in improving outcomes in patients receiving NMBA treatment.

Use of the AGREE II instrument to evaluate critical care practice guidelines addressing pharmacotherapy.

RATIONALE, AIMS AND OBJECTIVES: Clinical practice guidelines (CPGs) have been evaluated for reporting transparency and methodological quality in a number of studies in various disciplines, but few studies have focused on critical care and none on pharmacotherapy-related guidelines specifically. The objective of this study was to evaluate the quality of critical care CPGs with a focus on pharmacotherapy using the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. METHOD: A cross-sectional study of CPGs published from 2013 through August 2021 was conducted. Following establishment of interrater reliability, guidelines were independently evaluated by three reviewers to rate guidelines on criteria set forth by the AGREE II instrument. Domain scores and item scores were calculated using the AGREE II user manual, and results described with descriptive statistics. RESULTS: Out of 192 guidelines identified, 73 met inclusion criteria and were screened using the AGREE II instrument. Most guidelines were authored by a professional organization or government agency. Domain quality scores were calculated for each domain as recommended by the AGREE II instrument. Domain 4 (clarity of presentation) had the highest AGREE II domain score with a median score of 87.0% (interquartile range: 79.6%-92.6%). Domain 5 (applicability) received the lowest domain score with a mean score of 41.8 ± 21.1%. The majority of guidelines were recommended for use as published or with modifications, while only six guidelines (8.2%) were not recommended for use. CONCLUSIONS: The majority of critical care guidelines that include pharmacotherapy recommendations were recommended for use by study authors when the AGREE II instrument was applied. While guidelines generally scored highly in clarity of presentation, additional time and effort should focus on providing solutions to guideline implementation and inclusion of patient preferences.

Development of an evidence-based residency preparation checklist using a Delphi process.

PURPOSE: To develop an evidence-based tool that will provide concise guidance to pharmacy students who want to become competitive postgraduate year 1 (PGY1) residency applicants. METHODS: A systematic literature search was conducted to identify articles describing student or school factors and specific interventions or activities associated with improved or decreased residency match rates, as well as studies describing residency program directors' (RPDs') or preceptors' perceptions of qualified applicants. An initial checklist was developed, with an item for each relevant factor. A consensus on checklist items was built through a 2-round Delphi process with a panel of RPDs. Ultimately, items that received a median score of at least 5 on a 7-point scale with less than one-third of the ratings being a 1, 2, or 3 were included. RESULTS: The initial checklist of 34 items, primarily related to grade point average, professional involvement, work experience, or professional development, was evaluated by a panel of 25 RPD participants. Six of 34 items (18%) were reevaluated in round 2, along with 1 added item and 4 items substantively modified based on comments; 2 items were merged. Ultimately, 33 items met the criteria for consensus and were included in the final checklist. CONCLUSION: A checklist of items to guide prospective pharmacy residency applicants was developed through a systematic literature search and verified by program directors using a Delphi process.

Contemporary management of severe influenza disease in the intensive care unit.

Despite continued efforts to optimize vaccination composition, severe influenza disease requiring intensive care unit (ICU) admission remains a clinical issue. Influenza epidemics and pandemics worldwide continue to challenge clinicians with managing infected patients requiring ICU care. While routine use of antiviral therapy is deployed in ambulatory outpatients, their use in the ICU in patients with hypoxemic respiratory failure is less well established. Additionally, these therapies primarily target the neuraminidase protein, while contemporary research is increasingly demonstrating potential therapeutic benefits of targeting the hemagglutinin protein. These data have given rise to a growing interest in the use of immune modulating therapies for treatment of severe influenza. Additionally, pandemic outbreaks have revealed the growing need for salvage management, wherein lies the potential role for venovenous extracorporeal membrane oxygenation therapy in refractory respiratory failure. In this report, we review the contemporary ICU care of the severe influenza patient.

Dexmedetomidine for Alcohol Withdrawal Syndrome.

OBJECTIVE: To review available evidence evaluating dexmedetomidine in alcohol withdrawal syndrome (AWS) while identifying gaps in evidence for its use in this setting. DATA SOURCES: A MEDLINE search (1966-August 2015) to identify English-language articles evaluating the efficacy and safety of dexmedetomidine in alcohol withdrawal. Key words included alcohol, withdrawal, delirium tremens, and dexmedetomidine. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language observational studies, retrospective reviews, and clinical trials were included. Case reports and case series describing the use of dexmedetomidine in 10 or fewer patients were excluded. DATA SYNTHESIS: One randomized, controlled trial, 1 prospective observational study, and 6 retrospective reviews were identified. The only randomized, controlled trial identified showed that the addition of dexmedetomidine decreases benzodiazepine requirements more than placebo in the first 24 hours after initiation compared with the 24 hours prior to initiation (-56.8 mg vs -8 mg; P = 0.037). Overall, dexmedetomidine appears to lower benzodiazepine requirements in patients with AWS and decreases the sympathomimetic response seen in these patients. There was no convincing evidence that dexmedetomidine improves clinical endpoints in patients with AWS, such as need for mechanical ventilation or intensive care unit or hospital length of stay. CONCLUSIONS: Dexmedetomidine reduces hypertension and tachycardia in AWS and also reduces benzodiazepine requirements; however, the impact of these findings on important clinical endpoints is yet to be determined. Dexmedetomidine may be useful as adjunctive therapy; however, it cannot be recommended as a single agent in the management of AWS.

Administration of enteral nutrition to adult patients in the prone position.

OBJECTIVE: To examine the safety and efficacy of administering enteral nutrition (EN) to patients in the prone position. STUDY SELECTION AND DATA EXTRACTION: All English-language articles describing human studies identified from data sources were reviewed for inclusion. Included studies had to have at least two groups for comparison, one or all of which had to contain adult patients managed in the prone position. DATA SYNTHESIS: Four studies were identified that met our inclusion criteria. Only two of the included studies were specifically designed to compare outcomes associated with EN in the prone versus supine position. The remaining two studies did not specifically compare EN in the prone versus supine position, but did provide some insight on the tolerability of EN in the prone position. Overall, administration of EN to patients in the prone position results in gastric residual volumes similar to those seen in the supine position and does not appear to increase the risk of vomiting or ventilator associated pneumonia. CONCLUSIONS: There is limited evidence proving the safety and tolerability of EN administered to patients in the prone position; however, it does not substantially increase the rate of complications when compared to EN administered in the supine positioning.