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.

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.

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.

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.

Drug dosing in hospitalized obese patients with COVID-19.

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.

Identification of Risk Factors for Acute Kidney Injury from Intravenous Ketorolac in Geriatric Trauma Patients.

BACKGROUND: Ketorolac is an effective analgesic but the potential for acute kidney injury (AKI) is concerning, particularly in geriatric "G-60 trauma" patients. The objectives of this study are to report the incidence of AKI in patients who receive ketorolac, identify risk factors for AKI, and develop a risk factor-guided algorithm for safe utilization. METHODS: This retrospective cohort study included trauma patients age 60 years and older who received intravenous ketorolac. The primary endpoint was the incidence of AKI. RESULTS: Among 316 patients evaluated, the incidence of AKI was 2.5%. Patients with AKI received more nephrotoxins, had more comorbidities, and higher use of loop diuretics or vasopressors. Loop diuretic therapy and number of comorbidities were independent predictors of AKI. CONCLUSIONS: Risk for AKI with ketorolac was low, being more prevalent with comorbidities or receipt of loop diuretics.

Dosing Medications for Coagulopathy Reversal in Patients with Extreme Obesity.

BACKGROUND: The reversal of anticoagulant or antiplatelet medications is a priority in the management of patients with severe injury with the goal of minimizing further bleeding without thrombotic complications. There are few studies, however, evaluating the dosing of reversal agents in the setting of trauma specific to patients with extreme obesity. Nevertheless, clinicians must still make decisions, balancing concerns of ongoing bleeding with excessive thrombosis. OBJECTIVES: We describe the literature pertaining to dosing of medications used for the reversal of both drug-induced and trauma-related coagulopathy with the intent of providing a framework for clinicians to make dosing decisions in this challenging population. DISCUSSION: Obesity is known to impact both the volume of distribution and the clearance of medications, but these changes are not usually linear with size nor are they uniform across drugs. Current strategies for dosing reversal agents in obesity include a capped dose (e.g., prothrombin complex concentrates), fixed dosages (e.g., andexanet alfa, idarucizumab, and tranexamic acid), and weight-based dosing (e.g., desmopressin). Extreme obesity, however, was not highly prevalent in the studies that have validated these dosing strategies. In fact, many of the clinical studies fail to report the average weight of the patients included. CONCLUSION: Future studies should make efforts to increase reporting of patients with obesity included in clinical trials along with results stratified by weight class. In the meantime, doses listed in product labels should be used. Desmopressin should be dosed using either ideal body weight or a dose-capping strategy.

Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis.

Medications used for supportive care or prophylaxis constitute a significant portion of drug utilization in the intensive care unit. Evidence-based guidelines are available for many aspects of supportive care but drug doses listed are typically for patients with normal body habitus and not morbid obesity. Failure to account for the pharmacokinetic changes that occur with obesity can lead to an incorrect dose and treatment failure or toxicity. This paper is intended to help clinicians design initial dosing regimens in critically ill obese patients for medications commonly used for hemodynamic support or prophylaxis. A detailed literature search of medications used for supportive care or prophylaxis listed in practice guidelines was conducted with an emphasis on obesity, pharmacokinetics and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. For medications used for hemodynamic support, a similar strategy can be used as in non-obese patients. Similarly, medications for stress ulcer prophylaxis do not need to be adjusted. Anticoagulants for venous thromboembolism prophylaxis, on the other hand, require an individualized approach where higher doses are necessary.

Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium.

Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.

The Risk of Acute Kidney Injury in Critically Ill Patients Receiving Concomitant Vancomycin With Piperacillin-Tazobactam or Cefepime.

PURPOSE: The objective of this study was to compare the incidence of acute kidney injury (AKI) among critically ill patients receiving combination therapy with vancomycin plus piperacillin-tazobactam (VPT) against patients receiving vancomycin plus cefepime (VC). METHODS: A retrospective cohort study of adult patients admitted to an intensive care unit between September 2012 and December 2016 was conducted. Patients were included if they received combination therapy with VPT or VC for ≥48 hours. Patients were excluded if creatinine clearance was <60 mL/min or received renal replacement therapy prior to the initiation of therapy. The primary end point was AKI, as defined by the Acute Kidney Injury Network classification, during or within 48 hours of completion of therapy. The incidence of AKI was compared between groups and multivariate analysis was performed to control for relevant confounders. RESULTS: A total of 394 patients received either VPT (n = 258) or VC (n = 136). There were no differences in baseline serum creatinine (0.8 [0.3]mg/dL vs 0.7 [0.3] mg/dL, P = 0.207), use of vasopressors (44% vs 38%, P = 0.255), mechanical ventilation (45% vs 40%, P = 0.350), or initial vancomycin trough (11.2 [5] mg/L vs 11 [4.8] mg/L, P = 0.668) between VPT and VC groups, respectively. The incidence of AKI was 28.7% for VPT patients versus 21.3% for VC patients (P = 0.114). Multivariate analysis revealed vancomycin trough >20 mg/L (odds ratio, OR [95% confidence interval, CI] = 2.69 [1.62-4.47]), baseline SCr (OR [95% CI] = 3.34 [1.43-7.80]), vasopressors (OR [95% CI] = 1.77 [1.04-3.04]), and duration of combination therapy (OR [95% CI] = 1.009 [1.003-1.015]) as independent risk factors for AKI. CONCLUSION: The risk of AKI was similar between VPT and VC groups in critically ill patients. Risk factors for AKI were related to baseline renal function, duration of combination therapy, supratherapeutic vancomycin troughs, and severity of illness.

The Role of Desmopressin on Hematoma Expansion in Patients with Mild Traumatic Brain Injury Prescribed Pre-injury Antiplatelet Medications.

BACKGROUND/OBJECTIVE: Desmopressin (DDAVP) has been suggested for antiplatelet medication reversal in patients with traumatic brain injury (TBI) but there are limited data describing its effect on clinical outcomes. The purpose of this study was to evaluate the effect of DDAVP on hematoma expansion and thrombosis in patients with TBI who were prescribed pre-injury antiplatelet medications. METHODS: Consecutive adult patients who were admitted to our level I trauma center and prescribed pre-injury antiplatelet medications between July, 2012, and May, 2018, were retrospectively identified. Patients were excluded if their hospital length of stay was < 24 h, if DDAVP was administered by any route other than intravenous, if they received a DDAVP dose < 0.3 mcg/kg or there was no evidence of brain hemorrhage on computed tomography (CT) scan. Patients were stratified based on the use of DDAVP, and the incidence of hematoma expansion was compared between groups. Thrombotic events were reviewed as a secondary outcome. Multivariate analysis was utilized to control for confounding variables. RESULTS: Of 202 patients included in analysis, 158 (78%) received DDAVP. The mean age was 76 ± 12 years; the most common injury mechanism was falls (76%); 69% had acute subdural hematoma, and 49% had multi-compartmental hemorrhage. Initial Glasgow coma score was between 13 and 15 for 91% of patients. Aspirin was the most common antiplatelet regimen prescribed (N = 151, 75%), followed by dual antiplatelet regimens (N = 26, 13%) and adenosine diphosphate (ADP)-receptor inhibitors (N = 25, 12%). The incidence of hematoma expansion was 14% and 30% for patients who did and did not receive DDAVP, respectively (p = 0.015). After controlling for age, injury severity score, multi-compartmental hemorrhage, and receipt of pre-injury high-dose aspirin (> 81 mg), ADP-receptor inhibitors, oral anticoagulants, prothrombin complex concentrates or platelets in a multivariate analysis, the association between DDAVP and hematoma expansion remained significant (adjusted OR 0.259 [95% CI 0.103-0.646], p = 0.004). Thrombotic events were similar between the two groups (DDAVP, 2.5%, no DDAVP, 4.5%; p = 0.613). CONCLUSIONS: DDAVP was associated with a lower incidence of hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results justify a randomized controlled trial to further evaluate the role of DDAVP for this indication.

The SUP-ICU Trial: Does It Confirm or Condemn the Practice of Stress Ulcer Prophylaxis?

Purpose: Stress ulcer prophylaxis (SUP) is routinely administered to critically ill patients for the prevention of stress ulcer-induced, clinically important bleeding (CIB). Recently, the value of SUP has been questioned due to the perceived decline in CIB and the potential for infectious complications secondary to acid suppressive therapy. The SUP-ICU trial is a large, randomized controlled trial comparing intravenous pantoprazole with placebo for the indication of SUP. It is hoped that this trial would answer many of the questions pertaining to the overall value of SUP. This article will provide an in-depth assessment of the SUP-ICU trial in the context of the overall body of literature in this area. Furthermore, applications for clinical practice and recommendations on the provision of SUP are provided. Summary: The SUP-ICU trial revealed no difference in the primary outcome of 90-day mortality with pantoprazole but lower rates of CIB were noted (which was a secondary outcome). Overall, these data provide important insight into the value of SUP along with other questions related to the provision of SUP such as the relationship between CIB and mortality, infectious complications, and enteral nutrition. Conclusions: The SUP-ICU trial is a landmark trial describing the value of SUP in a modern-day setting of intensive care unit (ICU) practice. The provision of SUP should be continued in high-risk patients. Future studies are ongoing that will add further insight to this routine practice.

Stress Ulcer Prophylaxis in Neurocritical Care.

Stress ulcer prophylaxis (SUP) with acid-suppressive drug therapy is widely utilized in critically ill patients following neurologic injury for the prevention of clinically important stress-related gastrointestinal bleeding (CIB). Data supporting SUP, however, largely originates from studies conducted during an era where practices were vastly different than what is considered routine by today's standard. This is particularly true in neurocritical care patients. In fact, the routine provision of SUP has been challenged due to an increasing prevalence of adverse drug events with acid-suppressive therapy and the perception that CIB rates are sparse. This narrative review will discuss current controversies with SUP as they apply to neurocritical care patients. Specifically, the pathophysiology, prevalence, and risk factors for CIB along with the comparative efficacy, safety, and cost-effectiveness of acid-suppressive therapy will be described.

Stress Ulcer Prophylaxis.

OBJECTIVES: Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens. DATA SOURCES: A MEDLINE search was conducted from inception through August 2015. STUDY SELECTION: Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications. DATA EXTRACTION: Data from relevant publications were abstracted and summarized. DATA SYNTHESIS: The existing evidence is organized to describe the patients most likely to benefit from stress ulcer prophylaxis, review the comparative efficacy of proton pump inhibitors and histamine 2 receptor antagonists, the adverse effects of stress ulcer prophylaxis, and overall cost-effectiveness. CONCLUSIONS: Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues.