Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding - An Updated Meta-Analysis.

BACKGROUND: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. METHODS: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses. RESULTS: Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on Clostridioides difficile infection (low certainty). CONCLUSIONS: High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).

Consequences of anemia in geriatric hip fractures: how low is too low?

Background: The transfusion threshold for low hemoglobin (Hgb) in geriatric patients with hip fractures is widely debated. In certain populations, low Hgb is associated with poor outcomes. Our objective was to evaluate the relationship between lowest Hgb and outcome to identify the Hgb threshold where poor outcomes were more prevalent. Methods: This retrospective cohort study included consecutive patients with hip fractures, aged ≥60 years, evaluated at two level 1 trauma centers from 2018 to 2021. Patients who did not undergo operative fixation or had a length of stay <1 day were excluded. The primary endpoint was adverse outcome defined as the composite of myocardial infarction, stroke, new-onset arrhythmia or death. We compared lowest Hgb and possible confounders between patients with and without adverse outcomes. Classification and regression tree (CART) analysis was performed to identify the threshold for Hgb where adverse outcomes were more prevalent. Multivariate analysis was performed. Results: We evaluated 935 patients. Mean age was 80±10 years; admission Hgb was 12.5±1.7 g/dL. Diabetes was present in 20%, and 20% had coronary artery disease. Adverse outcomes were noted in 57 patients (6.1%). CART identified ≤7.1 g/dL as the Hgb threshold where adverse outcomes were more prevalent (15% vs. 4.1%, p<0.001). Additionally, a greater number of adverse outcomes were noted in the subgroup of patients having both a hemoglobin ≤7.1 g/dL and advanced age (age >79 years (22%)). After controlling for age, American Society of Anesthesiologist Physical Status Classification (ASA), antiplatelet medication, admission Hgb, time to operation and blood transfusions, lowest Hgb ≤7.1 g/dL remained a risk factor for adverse outcomes. Conclusions: In geriatric patients with isolated hip fractures, Hgb ≤7.1 g/dL is associated with a significantly higher rate of adverse outcomes. This risk was most pronounced in patients older than 79 years; particular care should be taken in this demographic. Level of evidence/study type: Level III/prognostic and epidemiological.

Management of Heat-Related Illness and Injury in the ICU: A Concise Definitive Review.

OBJECTIVES: The increasing frequency of extreme heat events has led to a growing number of heat-related injuries and illnesses in ICUs. The objective of this review was to summarize and critically appraise evidence for the management of heat-related illnesses and injuries for critical care multiprofessionals. DATA SOURCES: Ovid Medline, Embase, Cochrane Clinical Trials Register, Cumulative Index to Nursing and Allied Health Literature, and ClinicalTrials.gov databases were searched from inception through August 2023 for studies reporting on heat-related injury and illness in the setting of the ICU. STUDY SELECTION: English-language systematic reviews, narrative reviews, meta-analyses, randomized clinical trials, and observational studies were prioritized for review. Bibliographies from retrieved articles were scanned for articles that may have been missed. DATA EXTRACTION: Data regarding study methodology, patient population, management strategy, and clinical outcomes were qualitatively assessed. DATA SYNTHESIS: Several risk factors and prognostic indicators for patients diagnosed with heat-related illness and injury have been identified and reported in the literature. Effective management of these patients has included various cooling methods and fluid replenishment. Drug therapy is not effective. Multiple organ dysfunction, neurologic injury, and disseminated intravascular coagulation are common complications of heat stroke and must be managed accordingly. Burn injury from contact with hot surfaces or pavement can occur, requiring careful evaluation and possible excision and grafting in severe cases. CONCLUSIONS: The prevalence of heat-related illness and injury is increasing, and rapid initiation of appropriate therapies is necessary to optimize outcomes. Additional research is needed to identify effective methods and strategies to achieve rapid cooling, the role of immunomodulators and anticoagulant medications, the use of biomarkers to identify organ failure, and the role of artificial intelligence and precision medicine.

In-Hospital Violence and Its Impact on Critical Care Practitioners.

OBJECTIVES: To provide a narrative review of hospital violence (HV) and its impact on critical care clinicians. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing HV, risk factors, precipitating events, consequences, and mitigation strategies. STUDY SELECTION: Studies that specifically addressed HV involving critical care medicine clinicians or their practice settings were selected. The time frame was limited to the last 15 years to enhance relevance to current practice. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and abstracted data were parsed by setting, clinician type, location, social media events, impact, outcomes, and responses (agency, facility, health system, individual). DATA SYNTHESIS: HV is globally prevalent, especially in complex care environments, and correlates with a variety of factors including ICU stay duration, conflict, and has recently expanded to out-of-hospital occurrences; online violence as well as stalking is increasingly prevalent. An overlap with violent extremism and terrorism that impacts healthcare facilities and clinicians is similarly relevant. A number of approaches can reduce HV occurrence including, most notably, conflict management training, communication initiatives, and visitor flow and access management practices. Rescue training for HV occurrences seems prudent. CONCLUSIONS: HV is a global problem that impacts clinicians and imperils patient care. Specific initiatives to reduce HV drivers include individual training and system-wide adaptations. Future methods to identify potential perpetrators may leverage machine learning/augmented intelligence approaches.

A Systematic Approach to Understanding Acid-Base Disorders in the Critically Ill.

OBJECTIVE: The objective of this review is to discuss acid-base physiology, describe the essential steps for interpreting an arterial blood gas and relevant laboratory tests, and review the 4 distinct types of acid-base disorders. DATA SOURCES: A comprehensive literature search and resultant bibliography review of PubMed from inception through March 7, 2023. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language articles were extracted and evaluated. DATA SYNTHESIS: Critically ill patients are prone to significant acid-base disorders that can adversely affect clinical outcomes. Assessing these acid-base abnormalities can be complex because of dynamic aberrations in plasma proteins, electrolytes, extracellular volume, concomitant therapies, and use of mechanical ventilation. This article provides a systematic approach to acid-base abnormalities which is necessary to facilitate prompt identification of acid-base disturbances and prevent untoward morbidity and mortality. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Many acid-base disorders result from medication therapy or are treated with medications. Pharmacists are uniquely poised as the medication experts on the multidisciplinary team to assist with acid-base assessments in the context of pharmacotherapy. CONCLUSION: The use of a systematic approach to address acid-base disorders can be performed by all pharmacists to improve pharmacotherapy and optimize patient outcomes.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement From the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Critical Care Management of Patients After Cardiac Arrest: A Scientific Statement from the American Heart Association and Neurocritical Care Society.

The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

Reversal of pre-injury factor-Xa inhibitors with prothrombin complex concentrates in patients following traumatic brain injury.

INTRODUCTION: There is substantial debate on the best method to reverse factor Xa-inhibitors in patients following traumatic brain injury (TBI). Prothrombin complex concentrates (PCC) have been used for this indication but their role has been questioned. This study reported failure rates with PCC in patients following TBI and as a secondary objective, compared 4-factor (4 F-PCC) and activated PCC (APCC). MATERIAL AND METHODS: Consecutive patients with TBI on factor Xa-inhibitors admitted to one of two trauma centers were retrospectively identified. Patients with penetrating TBI, delays in PCC administration (>6 h), receipt of tranexamic acid, factor VIIa or no follow up CT-scan were excluded. The primary outcome was treatment failure defined as hematoma expansion > 20% from baseline for SDH, EDH or IPH, a new hematoma not present on the initial CT scan or any expansion of a SAH or IVH. Hematoma expansion was further categorized as symptomatic or asymptomatic, designated by a change in the motor GCS score, neurologic exam or change ≥ 3 in NIH Stroke Scale. Multi-variate analysis was performed. RESULTS: There were 43 patients with a mean age of 77 ± 13 years with primarily mild TBI (95%) after a ground level fall (79%). The mean dose was 41 ± 12 units/kg. Sixty percent received 4 F-PCC and 40% APCC. The incidence of treatment failure was 28% (12/43). Of the 12 patients with hematoma expansion, only 3 were symptomatic (9.3%). Hematoma expansion with 4 F-PCC and APCC were similar (27% vs. 29%,p = .859). Only sex was associated with hematoma expansion on multivariate analysis [OR (95% CI) = 6.7 (1.1 - 40.9)]. CONCLUSION: PCC was an effective option for factor Xa inhibitor reversal following TBI. The relationship between radiographic expansion and clinical expansion was poor.

Prophylactic acid suppression and enteral nutrition.

PURPOSE OF REVIEW: Stress ulcer prophylaxis (SUP) is routinely administered to critically ill patients who are at high-risk for clinically important gastrointestinal bleeding. Recent evidence however has highlighted adverse effects with acid suppressive therapy, particularly proton pump inhibitors where associations with higher mortality have been reported. Enteral nutrition may provide benefits in reducing the incidence of stress ulceration and may mitigate the need for acid suppressive therapy. This manuscript will describe the most recent evidence evaluating enteral nutrition for the provision of SUP. RECENT FINDINGS: There are limited data evaluating enteral nutrition for SUP. The available studies compare enteral nutrition with or without acid suppressive therapy rather than enteral nutrition vs. placebo. Although data exist demonstrating similar clinically important bleeding rates in patients on enteral nutrition who receive SUP vs. no SUP, these studies are underpowered for this endpoint. In the largest placebo-controlled trial conducted to date, lower bleeding rates were observed with SUP and most patients were receiving enteral nutrition. Pooled analyses had also described benefit with SUP vs. placebo and enteral nutrition did not change the impact of these therapies. SUMMARY: Although enteral nutrition may provide some benefit as SUP, existing data are not strong enough to validate their use in place of acid suppressive therapy. Clinicians should continue to prescribe acid suppressive therapy for SUP in critically ill patients who are at high risk for clinically important bleeding even when enteral nutrition is being provided.

Dilemmas Related to Direct-Acting Oral Anticoagulant Administration in Patients With Extreme Obesity.

OBJECTIVE: The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. DATA SOURCES: A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. STUDY SELECTION AND DATA ABSTRACTION: English-language studies and those conducted in adults were selected. DATA SYNTHESIS: The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. CONCLUSIONS: Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2.

Pharmacologic venous thromboembolism prophylaxis in obese trauma patients.

PURPOSE: To review the evidence cited in recent consensus documents providing recommendations for drug dosing for venous thromboembolism (VTE) prophylaxis in obese trauma patients. SUMMARY: Recent publications from the American Association for the Surgery of Trauma and the American College of Surgeons provide recommendations for VTE prophylaxis in trauma. These documents address key aspects of pharmacologic prophylaxis, one of which is drug dosing in obesity. Both documents provide recommendations for obese patients, but they were not formulated using Grading of Recommendations Assessment, Development and Evaluation methodology, which has become the standard approach for guideline development. We reviewed and critiqued the literature cited in recently published consensus documents along with identifying additional studies retrieved from a PubMed search pertaining to drug dosing for VTE prophylaxis in obesity. The overall body of evidence was reviewed, and caveats for application in the clinical setting are provided. Dosing strategies for obese trauma patients are largely extrapolated from studies conducted in nonobese patients. Studies evaluating clinical outcomes are limited as most rely on anti-factor Xa concentrations versus VTE occurrence. CONCLUSION: The strength of the evidence surrounding dosing recommendations for VTE prophylaxis in obese trauma patients is low. Further research efforts should be directed towards this subset of trauma patients.

Challenges With Using a Weight-Based Approach to Bolus Fluid Dosing in Obese Critically Ill Patients.

At least 30 mL/kg of crystalloid fluid administration within the first 3 hours of resuscitation is suggested by the current Surviving Sepsis Campaign guidelines for management of sepsis and septic shock. This commentary discusses the challenges with using a weight-based approach to bolus fluid dosing during the early phase of resuscitation of adult, obese patients. Based on the available literature, arguments can be made for the use of either ideal or adjusted body weight for weight-based fluid dosing, but there are concerns with fluid overload if using actual body weight to dose patients with more severe forms of obesity.

The safety of continuous fascia iliaca block in patients with hip fracture taking pre-injury anticoagulant and/or antiplatelet medications.

BACKGROUND: Fascia iliaca compartment block (FICB) is an effective method to treat pain in adult trauma patients with hip fracture. Of importance is the high prevalence of preinjury anticoagulants and antiplatelet medications in this population. To date, we have not identified any literature that has specifically evaluated the safety of FICB with continuous catheter infusion in patients on antiplatelet and/or anticoagulant therapy. The purpose of this study is to quantify the complication rate associated with FICB in patients who are actively taking prescribed anticoagulant and/or antiplatelet medications prior to injury and identify factors that may predispose patients to an adverse event. METHODS: This retrospective study included consecutive adult trauma patients (age ≥18) with hip fracture who underwent placement of FICB within 24 h of admission and had been taking anticoagulant and/or antiplatelet medications pre-injury. Patients were excluded if their catheter was placed more than 24 h post-hospital admission. Patients were evaluated for demographics, injury severity, laboratory values, medication history, receipt of coagulation-related reversal medications, and complications related to FICB placement. Complications included bleeding at the insertion site requiring catheter removal and 30-day catheter site infection. The incidence of complications was reported and risk factors for complications were identified using univariate and multivariate statistics. RESULTS: There were 124 patients included. The mean age was 81 ± 10 years, and the most common mechanism was ground level fall (94%). Most patients were taking single antiplatelet therapy (65%), followed by anticoagulant alone (21%), combined antiplatelet and anticoagulant therapy (7.3%) and dual antiplatelet therapy (7.3%). The most common antiplatelet was aspirin (88%) and the most common anticoagulant was warfarin (60%). Of the patients taking warfarin, the average INR on admission was 2.3 ± 0.8. Only 1 bleeding complication (0.8%) was noted in a patient prescribed clopidogrel pre-injury which occurred 5 days post-catheter placement. This same patient was noted to have superficial surgical site bleeding most likely secondary to the use of enoxaparin for post-operative deep venous thrombosis prophylaxis. There were 4 orthopedic superficial surgical site infections (3.2%), all remote from the catheter site. The pre-injury medication prescribed in these patients was aspirin 81 mg, aspirin 325 mg, rivaroxaban and dabigatran, respectively. No factors were associated with a complication thus multivariate analysis was not performed. CONCLUSION: The incidence of complications associated with fascia iliaca compartment block (FICB) in adult trauma patients prescribed pre-injury anticoagulants or antiplatelet medications is low. In this retrospective review, we did not identify any complications that were directly associated with the FICB procedure. Fascia iliaca block with continuous infusion catheter placement can be safely performed on patients who are on therapeutic anticoagulant and/or antiplatelet agents.

Pitfalls and pearls with drug dosing in the critically ill obese patient: 10 statements to guide ICU practitioners.

Obesity is highly prevalent in ICU patients presenting a number of challenges, one of which is drug dosing. There are limited high-quality data describing drug dosing in obesity, which can lead to dosing strategies that are suboptimal. For example, inappropriately using the wrong weight for weight-based dosing can lead to supratherapeutic drug concentrations and an adverse drug event or subtherapeutic drug concentrations and treatment failure. A generalized framework for decision making specific for obese patients is available that describes a step-by-step approach for constructing dosing regimens. This manuscript will build on that framework by providing pitfalls and pearls for clinicians to consider when making dosing decisions in critically ill patients with severe obesity.