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.

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.

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.

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.

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.

Determining the Clinical Utility of an Absolute Procalcitonin Value for Predicting a Positive Culture Result.

Various procalcitonin ranges have been established to guide antimicrobial therapy; however, there are no data that establish whether the initial procalcitonin value can determine the likelihood of a positive culture result. This study aimed to establish if the initial procalcitonin value, on clinical presentation, has a positive predictive value for any positive culture result. This was a retrospective study of 813 medical intensive care unit patients. Data collected included patient demographics, procalcitonin assay results, sources of infection, culture results, and lengths of stay. Patients were excluded if they were immunocompromised. The primary outcome of this study was to determine a procalcitonin value that would predict any positive culture. Secondary outcomes included the sensitivity, specificity, positive predictive value, and negative predictive value for procalcitonin. After exclusions, a total of 519 patient charts were reviewed to determine the impact of the initial procalcitonin value on culture positivity. In our analyses, the receiver operating characteristic values were 0.62 for all cultures, 0.49 for pulmonary infections, 0.43 for urinary tract infections, and 0.78 for bacteremia. A procalcitonin value of 3.61 ng/ml was determined to be the threshold value for a positive blood culture result (prevalence, 4%). For bacteremia, the sensitivity of procalcitonin was 75%, the specificity was 72%, the positive predictive value was 20%, and the negative predictive value was 97%. Procalcitonin was a poor predictor of culture positivity. An initial procalcitonin value of less than 3.61 ng/ml may be useful in predicting whether bacteremia is absent. Procalcitonin should not be used as the only predictor for determining initiation of antibiotic therapy.

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.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

OBJECTIVE: Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. DESIGN: Multicenter, observational study SETTING: : Medical ICUs at three academic medical centers. PATIENTS: Adult patients (age ≥ 18 yr old) receiving medication therapy. INTERVENTIONS: All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). CONCLUSION: Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

New-onset atrial fibrillation is an independent predictor of mortality in medical intensive care unit patients.

BACKGROUND: Atrial fibrillation (AF) has been extensively studied in postoperative critically ill surgical patients, but little literature exists to describe the outcomes of patients in the medical intensive care unit (ICU). OBJECTIVES: To determine the incidence of new-onset AF in patients admitted to a medical ICU and if new-onset AF was associated with adverse clinical outcomes. METHODS: This was a single-center, retrospective study of all adult patients admitted to the medical ICU at an academic medical center for >24 hours between December 2008 and April 2010. Collected data included past medical history, incidence of new-onset AF, Acute Physiology and Chronic Health Evaluation II scores, organ failure, length of stay in the ICU and hospital, and in-hospital and 60-day survival. RESULTS: A total of 741 patients were included. New-onset AF occurred in 53 patients (7.2%). In-hospital mortality was significantly greater for patients with new-onset AF (45% vs 16%; adjusted odds ratio [OR] = 2.21, 95% CI 1.07-4.54, P = 0.032), as was 60-day mortality (51% vs 23%; adjusted OR = 1.99, 95% CI = 1.01-3.91, P = 0.047). Patients with new-onset AF experienced greater ICU (6 ± 10.2 days vs 3 ± 3.6 days, P < 0.01) and hospital (15 ± 19 days vs 7 ± 9 days, P < 0.01) lengths of stay. CONCLUSIONS: Medical ICU patients who developed new-onset AF experienced a 2-fold increase in the odds of in-hospital mortality and death at 60 days. Further research investigating contributing factors to new-onset AF and potential treatments is warranted.

Off-label use of gastrointestinal medications in the intensive care unit.

PURPOSE: Determine the level of evidence supporting off-label gastrointestinal (GI) medication use and identify the medication class and indication whereby off-label use was most common. MATERIALS AND METHODS: This prospective, multicentered observational study evaluated all medication orders written in 37 intensive care units (ICUs) in the United States, over a 24-hour period. All medications classified as "GI" according to a national reference were identified. The class and indication whereby off-label use was most prominent were determined and the level of evidence was described. RESULTS: There were 774 orders from 363 patients and 63% (489 of 774) were considered off-label. Proton pump inhibitors (PPIs) accounted for most of the off-label usage (55% [271 of 489]), followed by laxatives (16% [77 of 489]) and histamine-2-receptor antagonists (H2RAs; 15% [71 of 489]). When prescribed, 99% (271 of 274) of PPIs, 99% (71 of 72) of H2RAs, and 79% (30 of 38) of promotility agents were off-label. Stress ulcer prophylaxis (100% [309 of 309]), GI bleeding (100% [18 of 18]), and gastric motility (88% [30 of 34]) were the most common off-label indications. The most common strength of recommendation and level of evidence for off-label use was indeterminate (58% [282 of 489]) and none (57% [280 of 489]), respectively. CONCLUSION: The PPIs are the most widely used off-label medications in the ICU. Stress ulcer prophylaxis is the most common indication. The level of evidence supporting off-label GI medication use is poor.

A comparison of initial monotherapy with norepinephrine versus vasopressin for resuscitation in septic shock.

BACKGROUND: Early goal-directed therapy is a time-sensitive therapeutic algorithm with a tiered approach to target hypoperfusion and cardiovascular collapse within the first 6 hours of septic shock. The Surviving Sepsis Campaign guidelines recommend norepinephrine or dopamine as the initial vasoactive agent for resuscitation in septic shock, reserving the administration of vasopressin as adjunctive therapy. OBJECTIVE: To determine whether vasopressin was noninferior to norepinephrine as the initial vasopressor to achieve a mean arterial pressure (MAP) goal in the first 6 hours of shock onset. METHODS: This retrospective cohort study evaluated adults who received monotherapy with either norepinephrine or vasopressin as initial vasoactive therapy for the management of septic shock. Patients were excluded if the treatment arm was not monotherapy, if they were admitted to a cardiology or cardiothoracic surgery service, or if they lacked a comparator-based 1:1 frequency matching. RESULTS: A total of 130 patients were included, 65 in each treatment arm. The proportion of patients who achieved a goal MAP in the vasopressin group was 63% (95% CI 51%-75%) and was 67.7% (95% CI 56%-79%) in the norepinephrine group. This observed difference between goal MAP attainment did not exceed the predefined noninferiority margin of -25% (CI for 4.7% difference -21.2% to 12%), suggesting noninferiority of vasopressin. No significant difference was identified between vasopressin and norepinephrine for final mean (SD) MAP achieved (75 [9.6] and 76.0 [8.2] mm Hg, respectively; p = 0.06) or the mean total change from baseline MAP to goal (14.1 [8.4] and 15.1 [9.1] mm Hg, respectively; p = 0.6). CONCLUSIONS: Vasopressin was noninferior to norepinephrine for the achievement of a MAP goal in the first 6 hours from onset of septic shock. Further prospective analysis is warranted; however, the results are useful for consideration of alternative vasopressors in the setting of drug shortages.

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.

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.

Drug-induced acute liver failure and gastrointestinal complications.

The objective of this article is to describe adverse drug events related to the liver and gastrointestinal tract in critically ill patients. PubMed and other resources were used to identify information related to drug-induced acute liver failure, gastrointestinal hypomotility, constipation, diarrhea, gastrointestinal bleeding, and pancreatitis in critically ill patients. This information was reviewed, and data regarding pathophysiology, common drug causes, and guidelines for prevention and management were collected and summarized. In cases in which data in critically ill patients were unavailable, data were extrapolated from other patient populations. Drug-induced acute liver failure can be caused by many drugs routinely used in the intensive care unit and may be associated with significant morbidity and mortality. Drug-related hypomotility and constipation and drug-related diarrhea are reported with many drugs, and these are common adverse drug events in critically ill patients that can substantially complicate the care of these patients. Drug-induced gastrointestinal bleeding and drug-induced pancreatitis occur less frequently, can range in disease severity, and can be associated with morbidity and mortality. Many drugs used in critically ill patients are associated with adverse drug events related to the liver and gastrointestinal tract. Critical care clinicians should be aware of common drug causes of drug-induced acute liver failure, gastrointestinal hypomotility, constipation, diarrhea, gastrointestinal bleeding, and pancreatitis, and should be familiar with the prevention and management of these diverse conditions.