Narrative Review: Addressing Covid-19 Vaccine Concerns in Special and Vulnerable Populations.

Public health advocates and healthcare professionals (HCPs) have been challenged with vaccine hesitancy and addressing misinformation. In order for HCPs and pharmacists, in particular, to serve as effective stewards of COVID-19 vaccine science in the interest of the public good, it is imperative for HCPs to appreciate the various factors contributing to vaccine hesitancy and vaccine distrust. A PubMed search was performed and relevant articles on COVID-19 vaccine in populations of interest were included. Information from health agencies, such as the Centers for Disease Control and Prevention (CDC) as well as established professional health societies was incorporated for guidance. This review focuses on COVID-19 vaccine concerns in the populations of children, pregnancy and lactation, immunocompromised, and religious and ethnic disparities. We also discuss post emergency use authorization experience with respect to vaccine safety including annotations on Guillain-Barré Syndrome, myocarditis and pericarditis, and thrombosis with thrombocytopenia syndrome.

Surviving Sepsis Campaign: Research Opportunities for Infection and Blood Purification Therapies.

Patients with infection can develop sepsis, and their mortality can be high. An important aspect in the treatment of sepsis is adequate management of the infection. DATA SOURCES: Using a modified Delphi approach, the Surviving Sepsis Campaign research committee recently published a series of 26 priorities for sepsis and septic shock. STUDY SELECTION: Task force members with specific expertise were tasked with generating expanded reviews for all infection questions and a subset of adjunctive therapy questions from the larger list of sepsis priorities. Each question was addressed by one of the six task force members. DATA EXTRACTION: In-depth reviews were then edited by the group as a whole, with added input from the committee cochairs. DATA SYNTHESIS: Six questions were addressed: 1) should empiric antibiotic combination therapy be used in sepsis or septic shock? 2) does optimization of antimicrobial pharmacokinetics and pharmacodynamics impact patient outcomes in sepsis? 3) should viral reactivation resulting from sepsis-induced immunosuppression be treated with antiviral therapy in critically ill septic patients? 4) should rapid diagnostic tests be implemented in clinical practice? 5) what is the role of lung-protective ventilation in sepsis patients without acute respiratory distress syndrome? and 6) how do we determine the efficacy of "blood purification" therapies such as endotoxin absorbers, cytokine absorbers, and plasmapheresis. CONCLUSIONS: The research committee members for the Surviving Sepsis Campaign aimed to explore research questions in order to provide existing evidence and highlight areas of uncertainty and future directions.

The Surviving Sepsis Campaign: Fluid Resuscitation and Vasopressor Therapy Research Priorities in Adult Patients.

OBJECTIVE: Expand upon the priorities of fluid resuscitation and vasopressor therapy research priorities identified by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Original article, literature search. STUDY SELECTION: Several members of the original task force with expertise specific to the area of fluid resuscitation and vasopressor therapy. DATA EXTRACTION: None. DATA SYNTHESIS: None. CONCLUSION: In the second of a series of manuscripts subsequent to the original article, members with expertise in the subjects expound upon the three identified priorities related to fluid resuscitation and vasopressor therapies. This analysis summarizes what is known and what were identified as ongoing and future research.

The surviving sepsis campaign: fluid resuscitation and vasopressor therapy research priorities in adult patients.

OBJECTIVE: To expand upon the priorities of fluid resuscitation and vasopressor therapy research priorities identified by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Original paper and literature search. STUDY SELECTION: Several members of the original task force with expertise specific to the area of fluid resuscitation and vasopressor therapy. DATA EXTRACTION: None. DATA SYNTHESIS: None. CONCLUSION: In the second of a series of manuscripts subsequent to the original paper, members with expertise in the subjects expound upon the three identified priorities related to fluid resuscitation and vasopressor therapies. This analysis summarizes what is known and what were identified as ongoing and future research.

Characterizing Critical Care Pharmacy Services Across the United States.

Involvement of clinical pharmacists in the ICU attenuates costs, avoids adverse drug events, and reduces morbidity and mortality. This survey assessed services and activities of ICU pharmacists. DESIGN: A 27-question, pretested survey. SETTING: 1,220 U.S. institutions. SUBJECTS: Critical care pharmacists. INTERVENTIONS: Electronic questionnaire of pharmacy services and activities across clinical practice, education, scholarship, and administration. MEASUREMENTS AND MAIN RESULTS: A total of 401 (response rate of 35.4%) surveys representing 493 ICUs were completed. Median daily ICU census was 12 (interquartile range, 6-20) beds with 1 (interquartile range, 1-1.5) pharmacist full-time equivalent per ICU. Direct clinical ICU pharmacy services were available in 70.8% of ICUs. Pharmacists attended rounds 5 days (interquartile range, 4-5 d) per week with a median patient-to-pharmacist ratio of 17 (interquartile range, 12-26). The typical workweek consisted of 50% (interquartile range, 40-60%) direct ICU patient care, 10% (interquartile range, 8-16%) teaching, 8% (interquartile range, 5-18%) order processing, 5% (interquartile range, 0-20%) direct non-ICU patient care, 5% (interquartile range, 2-10%) administration, 5% (interquartile range, 0-10%) scholarship, and 0% (interquartile range, 0-5%) drug distribution. Common clinical activities as a percentage of the workweek were reviewing drug histories (28.5%); assessing adverse events (27.6%); and evaluating (26.1%), monitoring (23.8%), and managing (21.4%) drug therapies. Services were less likely to occur overnight or on weekends. Telemedicine was rarely employed. Dependent prescriptive authority (per protocol or via practice agreements) was available to 51.1% of pharmacists and independent prescriptive authority was provided by 13.4% of pharmacists. Educational services most frequently provided were inservices (97.6%) and experiential training of students or residents (89%). Education of ICU healthcare members was provided at a median of 5 times/mo (interquartile range, 3-15 times/mo). Most respondents were involved with ICU or departmental policies/guidelines (84-86.8%) and 65.7% conducted some form of scholarship. CONCLUSIONS: ICU pharmacists have diverse and versatile responsibilities and provide several key clinical and nonclinical services. Initiatives to increase the availability of services are warranted.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and makes recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services: 2020 Update.

OBJECTIVES: To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and make recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-System Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (>66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Vasoactive Agent Use in Septic Shock: Beyond First-Line Recommendations.

Septic shock is a life-threatening disorder associated with high mortality rates requiring rapid identification and intervention. Vasoactive agents are often required to maintain goal hemodynamics and preserve tissue perfusion. However, guidance regarding the proper administration of adjunct agents for the management of septic shock is limited in patients who are refractory to norepinephrine. This review summarizes vasopressor agents and describes the nuanced application of these agents in patients with septic shock, specifically focusing on clinical scenarios with limited guidance including patients who are nonresponsive to first-line agents and individuals with mixed shock states, tachyarrhythmias, obesity, valvular abnormalities, or other comorbid conditions.

Scoping Review of Interventions Associated with Cost Avoidance Able to Be Performed in the Intensive Care Unit and Emergency Department.

A framework for evaluating pharmacists' impact on cost avoidance in the intensive care unit (ICU) and emergency department (ED) has not been established. This scoping review was registered (CRD42018091217) and conducted to identify, aggregate, and qualitatively describe the highest quality evidence for cost avoidance generated by clinical pharmacists on interventions performed in an ICU or ED. Searches were conducted in PubMed, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until April 2018. The level of evidence (LOE) for each specific category of intervention was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation evidence-to-decision framework. The risks of bias for articles were evaluated using Newcastle Ottawa and Cochrane Collaboration tools. The values from all interventions were inflated to 2018 U.S. dollars using the consumer price index for medical care. Of the 464 articles initially identified, 371 were excluded and 93 were included. After reviewing references from the articles included, an additional 71 articles were also reviewed. The 38 cost intervention categories were supported by varying LOEs: IA (0 categories), IB (1 category), IIA (4 categories), IIB (0 categories), III (27 categories), and IV (6 categories), and articles mostly displayed low to moderate risks of bias. Pharmacists generate cost avoidance through a variety of interventions in critically and emergently ill patients. The quality of evidence supporting specific cost avoidance values is generally low. Quantification of and factors associated with the cost avoidance generated from pharmacists caring for these patients are of paramount importance.

A Multicenter, Prospective, Observational Study to Determine Predictive Factors for Multidrug-Resistant Pneumonia in Critically Ill Adults: The DEFINE Study.

OBJECTIVE: This study was conducted to describe the prevalence, epidemiology, and clinical outcomes of multidrug-resistant (MDR) organism (MDRO) pneumonia in critically ill patients. METHODS: A multicenter, prospective, observational study of patients admitted to 60 intensive care units (ICUs), from 34 hospitals, in the United States from November to December 2016. Adults (> 18 yrs) receiving antimicrobial therapy at least 5 days for pneumonia were included. Patients were classified into two categories, with or without MDRO, and subcategorized by pneumonia type. MEASUREMENTS AND MAIN RESULTS: Demographics, medication histories, and health care exposure were collected during ICU admission and compared using t test and chi-square tests. Multivariate logistic regression was used to determine predictive factors for MDRO pneumonia and hospital mortality. Of 652 patients, 92 patients (14.1%) developed MDR pneumonia. Predictors of MDRO pneumonia were acid suppression therapy within the previous 90 days (odds ratio [OR] 1.88 [1.14-3.09]; p=0.013), mechanical ventilation (OR 1.96 [1.14-3.35]; p<0.001), and history of MDRO infection (OR 4.74 [2.21-10.18]; p<0.001). Appropriate initial antimicrobial selection occurred in 58 patients (63%) with MDRO pneumonia compared to 464 patients (82.7%) in patients without MDRO pneumonia (p<0.001). MDRO pneumonia was not associated with hospital mortality (18.5% vs 17.6%, p=0.087). CONCLUSIONS: In a broad cohort of critically ill patients, MDRO pneumonia is infrequent, and associated with factors describing the intensity of health care provided. Presence of MDRO pneumonia is not associated with hospital mortality. Further study is needed to clarify risk factors for multidrug-resistant pneumonia in critically ill patients.

Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies.

Background: Clinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published. Objective: To assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use. Methods: A scenario-based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi-square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups. Results: Among 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045). Conclusion: Since vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.

Surviving sepsis campaign: research priorities for sepsis and septic shock.

OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock.

OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: 1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; 2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; 3) should rapid diagnostic tests be implemented in clinical practice?; 4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; 5) what are the predictors of sepsis long-term morbidity and mortality?; and 6) what information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Effects of Chronic Antihypertensives on Vasopressor Dosing in Septic Shock.

BACKGROUND: In septic shock, chronic antihypertensive medications are held acutely. Vasopressors are often required to maintain blood pressure. The effect of chronic exposure to antihypertensive therapies on vasopressor dosing in septic shock is not known. OBJECTIVE: To determine the effects of chronic exposure to antihypertensive therapies, specifically ß-blockers and angiotensin-converting enzyme (ACE) inhibitors, on cumulative vasopressor dosing in septic shock. METHODS: This was a retrospective cohort review, with data collected from routine care. Patients admitted to the medical intensive care unit with septic shock and vasopressor use were included and divided into 4 groups based on chronic medication use: (1) no ß-blocker or ACE inhibitor, (2) ß-blocker only, (3) ACE inhibitor only, and (4) ß-blocker and ACE inhibitor. Cumulative vasopressor dose at 48 hours was assessed. Demographics, comorbid conditions, suspected site of infection, disease severity, mortality, and concomitant therapies were evaluated between groups. RESULTS: A total of 133 patients with septic shock treated with vasopressors were included. No difference in cumulative vasopressor dose at 48 hours was detected between the 4 groups, respectively (median norepinephrine milligram equivalents [interquartile range (IQR)]: no ß-blocker or ACE inhibitor, 13.7 mg [6.0-35.7]; ß-blocker only, 13.1 mg [5.4-23.9]; ACE inhibitor only, 13.2 mg [1.2-36.7]; ß-blocker and ACE inhibitor, 11.3 mg [4.7-42.9]; P = 0.669). Total time on vasopressors differed between groups (median hours [IQR]: no ß-blocker or ACE inhibitor, 30h [17-60]; ß-blocker only, 24h [10-69]; ACE inhibitor only, 19h [6-25]; ß-blocker and ACE inhibitor, 30h [15-58]; P = 0.031). Comorbid conditions, suspected infection sites, disease severity, mortality, and concomitant therapies were similar. CONCLUSIONS: Chronic ß-blocker, ACE inhibitor use, or the combination of both did not affect cumulative vasopressor dose at 48 hours in septic shock. However, prior-to-admission medications may affect total time of vasopressor use.

Characterization of Guideline Evidence for Off-label Medication Use in the Intensive Care Unit.

BACKGROUND: Non-Food and Drug Administration (FDA) or off-label medication prescribing occurs commonly in the intensive care unit (ICU). Off-label medication use creates a concern for untoward adverse effects; however, this worry may be alleviated by supportive literature. OBJECTIVE: To evaluate the evidence behind off-label medication use by determining the presence of guideline support and compare graded recommendations to an online tertiary resource, DRUGDEX. METHODS: Off-label medication use was identified prospectively over 3 months in medical ICUs in 3 academic medical centers. Literature searches were conducted in PubMed and the national guideline clearinghouse website to determine the presence of guideline support. DRUGDEX was also searched for strength-of-evidence ratings to serve as a comparator. RESULTS: A total of 287 off-label medication indication searches resulted in 44% (126/287) without identified evidence; 253 guidelines were identified for 56% (161/287) of indications. Of the published guidelines, 89% (226/253) supported the off-label indication. In the DRUGDEX comparison, 67% (97/144) of guideline gradings disagree with DRUGDEX, whereas 33% (47/144) of the gradings matched the online database. CONCLUSION: Because more than half of off-label medication use has the benefit of supportive guidelines recommendations and a majority of gradings are inconsistent with DRUGDEX, clinicians should consider utilizing guidelines to inform off-label medication use in the ICU. Still, there is a considerable amount of off-label medication use in the ICU that lacks supporting evidence, and use remains concerning because it may lead to inappropriate treatment and adverse events.