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Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality utilized in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most utilized anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on co-factors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of co-factors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. Additionally, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification., Competing Interests: Disclosure and funding: The authors report no conflicts of interest relevant to this manuscript and no funding was received., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There has been an evolution in the disease severity and complexity of patients presenting to the cardiac intensive care unit (CICU). There are limited data evaluating the role of palliative care in contemporary CICU practice., Methods: PubMed Central, CINAHL, EMBASE, Medline, Cochrane Library, Scopus, and Web of Science databases were evaluated for studies on palliative care in adults (≥18 years) admitted with acute cardiovascular conditions - acute myocardial infarction, cardiogenic shock, cardiac arrest, advanced heart failure, post-cardiac surgery, spontaneous coronary artery dissection, Takotsubo cardiomyopathy, and pulmonary embolism - admitted to the CICU, coronary care unit or cardiovascular intensive care unit from 1/1/2000 to 8/8/2022. The primary outcome of interest was the utilization of palliative care services. Secondary outcomes of included studies were also addressed. Meta-analysis was not performed due to heterogeneity., Results: Of 5711 citations, 30 studies were included. All studies were published in the last seven years and 90 % originated in the United States. Twenty-seven studies (90 %) were retrospective analyses, with a majority from the National Inpatient Sample database. Heart failure was the most frequent diagnosis (47 %), and in-hospital mortality was reported in 67 % of studies. There was heterogeneity in the timing, frequency, and background of the care team that determined palliative care consultation. In two randomized trials, there appeared to be improvement in quality of life without an impact on mortality., Conclusions: Despite the growing recognition of the role of palliative care, there are limited data on palliative care consultation in the CICU., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Regardless of the type, extracorporeal membrane oxygenation (ECMO) requires the use of large intravascular cannulas and results in multiple abnormalities including non-physiologic blood flow, hemodynamic perturbation, rapid changes in blood oxygen and carbon dioxide levels, coagulation abnormalities, and a significant systemic inflammatory response. Among other sequelae, neurologic complications are an important source of mortality and long-term morbidity. The frequency of neurologic complications varies and is likely underreported due to the high mortality rate. Neurologic complications in patients supported by ECMO include ischemic and hemorrhagic stroke, hypoxic brain injury, intracranial hemorrhage, and brain death. In addition to the disease process that necessitates ECMO, cannulation strategies and physiologic disturbances influence neurologic outcomes in this high-risk population. For example, the overall documented rate of neurologic complications in the venovenous ECMO population is lower, but a higher rate of intracranial hemorrhage exists. Meanwhile, in the venoarterial ECMO population, ischemia and global hypoperfusion seem to compose a higher percentage of neurologic complications. In what follows, the literature is reviewed to discuss the pathophysiology, incidence, risk factors, and outcomes related to short-term neurologic complications in patients supported by ECMO., (© 2024. The Author(s).)

Interest in remimazolam has surged in recent years, thanks to its advantageous pharmacologic profile. This ultra-short-acting benzodiazepine is noted for its rapid onset and termination of action, organ-independent elimination, availability of a reversal agent, and excellent hemodynamic stability. Although the use of remimazolam has been explored in various anesthesia settings and procedures, data on its application in cardiovascular anesthesia and catheterization laboratory procedures remain limited. This review evaluates the latest literature to assess remimazolam's role in cardiovascular anesthesia across different settings and procedures. The analysis shows that remimazolam offers anesthesia without significant hemodynamic instability and a reduced need for vasopressors, with an incidence of perioperative adverse events comparable to that of other agents. These findings are relevant for both the induction and maintenance of general anesthesia in catheterization laboratory procedures and general anesthesia in elective cardiac surgery. Although further research is needed to fully understand remimazolam's role in cardiovascular anesthesia, its favorable hemodynamic and safety profile suggests that it is a promising option for cardiac anesthesiologists in both the catheterization laboratory and the operating room., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85-13.20) seconds compared to only a 3.81 (95% CI = 1.55-6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) ( pinteraction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38-5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05-1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63-0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25-0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82-0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin's hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Epinephrine is recommended without an apparent ceiling dosage during cardiac arrest. However, excessive alpha- and beta-adrenergic stimulation may contribute to unnecessarily high aortic afterload, promote post-arrest myocardial dysfunction, and result in cerebral microvascular insufficiency in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR)., Methods: This was a retrospective cohort study of adults (≥ 18 years) who received ECPR at large academic ECMO center from 2018 to 2022. Patients were grouped based on the amount of epinephrine given during cardiac arrest into low (≤ 3 mg) and high (> 3 mg) groups. The primary endpoint was neurologic outcome at hospital discharge, defined by cerebral performance category (CPC). Multivariable logistic regression was used to assess the relationship between cumulative epinephrine dosage during arrest and neurologic outcome., Results: Among 51 included ECPR cases, the median age of patients was 60 years, and 55% were male. The mean cumulative epinephrine dose administered during arrest was 6.2 mg but ranged from 0 to 24 mg. There were 18 patients in the low-dose (≤ 3 mg) and 25 patients in the high-dose (> 3 mg) epinephrine groups. Favorable neurologic outcome at discharge was significantly greater in the low-dose (55%) compared to the high-dose (24%) group (p = 0.025). After adjusting for age, those who received higher doses of epinephrine during the arrest were more likely to have unfavorable neurologic outcomes at hospital discharge (odds ratio 4.6, 95% CI 1.3, 18.0, p = 0.017)., Conclusion: After adjusting for age, cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurologic outcomes after ECPR and require further investigation., Competing Interests: Declaration of competing interest The authors of the manuscript titled “Cumulative Epinephrine Dose during Cardiac Arrest and Neurologic Outcome after Extracorporeal Cardiopulmonary Resuscitation” submitted to “The American Journal of Emergency Medicine,” affirm that we have no conflicts of interest to declare. There are no financial interests or personal/professional relationships that could reasonably be perceived as influencing the integrity or objectivity of the research presented in this manuscript. We understand the importance of transparency in maintaining the credibility of scientific publications and commit to promptly notify the editorial board of “The American Journal of Emergency Medicine” should any conflicts of interest arise post-submission., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice., Design: Review and task force position statements with necessary guidance., Setting: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem., Subjects: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine., Interventions: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided., Measurements and Main Results: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences., Conclusions: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders., Competing Interests: Dr. Wieruszewski received funding from La Jolla Pharmaceutical Company. Dr. De Waele’s institution received funding from Menarini, MSD, Pfizer, Thermofisher, and Viatris. Dr. Leone received funding from LFB, Viatris, and Shionigi. Dr. Messina received funding from Vygon, Edwards, and Philips. Dr. McKenzie’s institution received funding from the National Institute of Health and Social Care Research, Wessex Applied Research Collaborative, and Pharmaceutical Press; she received funding from Sedana Medical and Southampton Research Leaders Programme. Ashish K. Khanna’s institution received funding from La Jolla Pharmaceuticals, Trevena Pharmaceuticals, and Edwards LifeSciences. He receives consulting fees from Medtronic, Edwards LifeSciences, Philips Research North America, GE Healthcare, Potrero Medical, Retia Medical, Pharmazz Inc. and Caretaker Medical. He receives grant funding from Hypertension and Vascular Research Center at the Wake Forest University School of Medicine (AG073581) to study mechanisms of renin dysregulation in shock. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Competing Interests: Declaration of Competing Interest None.

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century. Recently, a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres, finding diverse applications in intensive care settings. In the dynamic landscape of intensive care, volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements, managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus, conditions of high sedative requirements including burns, high opioid or alcohol use and neurological conditions such as status epilepticus. Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry, providing intensivists with multiple options to tailor therapy. Furthermore, their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy, mitigating risks associated with conventional sedation modalities. Despite the amounting enthusiasm for the use of these therapies, barriers to widespread utilization include expanding equipment availability, staff familiarity and training of safe use. This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology, administration considerations in intensive care settings, complication considerations, and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vasoplegic shock after cardiac surgery is characterized by hypotension, a high cardiac output, and vasodilation. Much of the understanding of this pathologic state is informed by the understanding of septic shock. Adverse outcomes and mortality are increased with vasoplegic shock. Early recognition and a systematic approach to its management are critical. The need for vasopressors to sustain an adequate blood pressure as well as pharmacologic adjuncts to mitigate the inflammatory inciting process are necessary. The rationale behind vasopressor escalation and consideration of adjuncts are discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study described the outcomes of patients receiving topical, nebulized, endobronchial, or systemic tranexamic acid (TXA) for bleeding events while on extracorporeal membrane oxygenation (ECMO). We performed a single-center case series including adult patients >18 years old supported on either venovenous (VV) or venoarterial (VA) ECMO from January 1, 2014, to April 21, 2021. The primary outcome was hemostatic control defined as a composite of initial cessation of therapeutic interventions to mitigate bleeding or resumption of anticoagulation if previously held. Secondary outcomes included changes in transfusion requirements and lysis at 30-minute (LY30) values, venous thromboembolism (VTE) events, and seizures. In total, 47 patients were included for full analysis. There were 19 patients with surgical bleeds, 18 patients with medical bleeds, and 10 patients with multiple bleeds. Overall, initial hemostatic control was achieved in 79%, 67%, and 90% of patients, respectively. Pre- and post-TXA transfusion requirements were not significantly different ( p = 0.2), although the intraindividual change in median LY30 was -5.1% compared with baseline (95% confidence interval [CI], -12.4% to -1.5%, p = 0.005). The occurrence of VTE and seizures was relatively low and similar among patient bleeding groups. Tranexamic acid provided initial hemostatic control in roughly three quarters of patients with bleeding events on ECMO and side effects were infrequent., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Objectives: Hydroxocobalamin inhibits nitric oxide pathways contributing to vasoplegic shock in patients undergoing cardiopulmonary bypass (CPB). The objective of this study was to evaluate the effect of intraoperative versus postoperative application of hydroxocobalamin for vasoplegic shock in patients undergoing CPB., Design: This was a historic cohort study., Setting: The study was conducted at a quaternary academic cardiovascular surgery program., Participants: Adults undergoing cardiac surgery using CPB were participants in the study., Interventions: Hydroxocobalamin (5 g) intravenously over 15 minutes., Measurements and Main Results: The treatment groups were assigned based on the receipt location of hydroxocobalamin (ie, intensive care unit [ICU] versus operating room [OR]). The primary outcome was vasopressor-free days in the first 14 days after CPB. Of the 112 patients included, 37 patients received hydroxocobalamin in the OR and 75 in the ICU. Patients in the OR group were younger than those in the ICU group (57.5 v 63.9 years, p = 0.007), with statistically similar American Society of Anesthesiologists scores. The mean CPB duration was 3.4 hours in the OR group and 2.9 hours in the ICU group (p = 0.09). In both groups, the norepinephrine-equivalent dose of vasopressors at hydroxocobalamin was 0.27 µg/kg/min. Days alive and free of vasopressors were not different between the OR and ICU groups (estimated difference 0.48 [95% CI -1.76-2.72], p = 0.67). The odds of postoperative renal failure, mesenteric ischemia, ICU, hospital length of stay, and in-hospital mortality were also similar between groups., Conclusions: A difference in vasopressor-free days after CPB was not found between patients who received hydroxocobalamin intraoperatively versus postoperatively for vasoplegic shock., Competing Interests: Declaration of Competing Interest E.D.W. serves as a consultant for Pacira Biosciences, Inc. P.M.W. has previously served as a consultant for La Jolla Pharmaceutical Company. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tris-hydroxymethyl aminomethane (THAM) is an amino alcohol used clinically to buffer acid loads and raise pH in acidotic conditions. Unlike sodium bicarbonate, which increases plasma sodium levels with use and produces carbon dioxide (CO 2 ) as part of the buffering process, THAM does neither. Although not widely used in modern critical care and unavailable for clinical use in 2016, THAM has been available in the United States since 2020. Clinical experience and existing literature suggest that THAM may have clinical utility in acid-base management in conditions such as liver transplantation where rising sodium levels during perioperative care may be dangerous, and in managing acid-base derangements during care of patients with acute respiratory distress syndrome (ARDS). To clarify the evidence base supporting the clinical use of THAM, we conducted a systematic review to assess the efficacy and safety of THAM as a buffering agent in critically ill adults using Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection. Randomized-, crossover-, retrospective cohort-, parallel-designed clinical trials, case series, and case reports of adult patients who received THAM in the operative or critical care setting were included. Conference abstracts of qualifying study designs were also included. Two independent reviewers extracted the data regarding the study details, demographics, treatment, and outcomes data. A third reviewer adjudicated discrepancies. A total of 21 studies including 3 randomized controlled trials, 5 observational studies, 4 case series, and 9 case reports met inclusion criteria. Eight studies (38%) were abstracts published in conference proceedings. In total, 417 critically ill patients received THAM to treat acidosis in critically ill surgical and nonsurgical patients, during liver transplantation, and in ARDS. In general, THAM corrected acidosis with an efficacy equivalent to sodium bicarbonate and did so with less hypercarbia and hypernatremia. Adverse effects of THAM included hyperkalemia, hypoglycemia, ventilator depression, and tissue damage with extravasation. We conclude that THAM may have potential advantages in some critical care settings, but that clinical evidence is limited, and high-quality evaluations are necessary., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Introduction: High-dose catecholamines can impair hypoxic pulmonary vasoconstriction and increase shunt fraction. We aimed to determine if Angiotensin II (Ang-2) is associated with improved PaO 2 /FiO 2 and SpO 2 /FiO 2 in patients in shock., Methods: Adult patients at four tertiary care centers and one community hospital in the United States who received Ang-2 from July 2018-September 2020 were included in this retrospective, observational cohort study. PaO 2 , SpO 2 , and FiO 2 were measured at 13 timepoints during the 48-h before and after Ang-2 initiation. Piecewise linear mixed models of PaO 2 /FiO 2 and SpO 2 /FiO 2 were created to evaluate hourly changes in oxygenation after Ang-2 initiation. The difference in the proportion of patients with PaO 2 /FiO 2  ≤ 300 mm Hg at the time of Ang-2 initiation and 48 h after was also examined., Results: The study included 254 patients. In the 48 h prior to Ang-2 initiation, oxygenation was significantly declining (hourly PaO 2 /FiO 2 change -4.7 mm Hg/hr, 95% CI - 6.0 to -3.5, p  < .001; hourly SpO 2 /FiO 2 change -3.1/hr, 95% CI-3.7 to -2.4, p  < .001). Ang-2 treatment was associated with significant improvements in PaO 2 /FiO 2 and SpO 2 /FiO 2 in the 48-h after initiation (hourly PaO 2 /FiO 2 change +1.5 mm Hg/hr, 95% CI 0.5-2.5, p   =  .003; hourly SpO 2 /FiO 2 change +0.9/hr, 95% CI 0.5-1.2, p  < .001). The difference in the hourly change in oxygenation before and after Ang-2 initiation was also significant ( p interaction  < 0.001 for both PaO 2 /FiO 2 and SpO 2 /FiO 2 ). This improvement was associated with significantly fewer patients having a PaO 2 /FiO 2  ≤ 300 mm Hg at 48 h compared to baseline (mean difference -14.9%, 95% CI -25.3% to -4.6%, p   =  .011). Subgroup analysis found that patients with either a baseline PaO 2 /FiO 2  ≤ 300 mm Hg or a norepinephrine-equivalent dose requirement >0.2 µg/kg/min had the greatest associations with oxygenation improvement., Conclusions: Ang-2 is associated with improved PaO 2 /FiO 2 and SpO 2 /FiO 2 . The mechanisms for this improvement are not entirely clear but may be due to catecholamine-sparing effect or may also be related to improved ventilation-perfusion matching, intrapulmonary shunt, or oxygen delivery.

Objectives: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022., Data Sources: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update., Study Selection: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article., Data Extraction: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature., Data Synthesis: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia., Conclusions: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue., Competing Interests: Conflict of Interest EDW serves as a consultant for Pacira Biosciences, Inc. PMW has previously served as a consultant for La Jolla Pharmaceutical Company. All other authors declare no conflict of interest or sources of funding related to the content of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Beta-lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta-lactam TDM program. This single-center experience forms the basis of the manuscript which outlines practical considerations involved with implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist-led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of 'individual internalization' seems to be uniquely important to beta-lactam TDM implementation compared with implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist led beta-lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program., Competing Interests: Competing interests: PMW has previously served as a consultant for La Jolla Pharmaceutical Company. EFB consults for Wolters Kluwer. All other authors declare that they have no competing interests or relevant conflicts of interest to disclose.

Purpose: To describe the use of mechanical circulatory support in the setting of cardiac arrest and summarize pharmacists' role in extracorporeal cardiopulmonary resuscitation (ECPR)., Summary: ECPR is increasingly used to reduce morbidity and improve mortality after cardiac arrest. ECPR employs venoarterial ECMO, which provides full circulatory perfusion and gas exchange in both adult and pediatric patients in cardiac arrest. After the emergency medicine team identifies potential candidates for ECPR, the ECMO team is consulted. If deemed a candidate for ECPR by the ECMO team, the patient is cannulated during ongoing standard cardiopulmonary resuscitation. A multidisciplinary team of physicians, nurses, perfusionists, pharmacists, and support staff is needed for successful ECPR. Pharmacists play a vital role in advanced cardiac life support (ACLS) prior to cannulation. Pharmacists intervene to make pharmacotherapy recommendations during ACLS, prepare medications, and administer medications as allowed by institutional and state regulations. Pharmacists also provide pharmacotherapy support in the selection of anticoagulation agents, ongoing vasopressor administration during ECMO cannulation, and the optimization of medication selection in the peri-ECPR period., Conclusion: With the growing use of ECPR, pharmacists should be aware of their role in medication optimization during ECPR., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Early initiation of a multimodal treatment strategy in the management of vasopressors during septic shock has been advocated to reduce delays in restoring adequate organ perfusion and to mitigate side effects associated with the administration of high-dose catecholamines. We provide a review that summarises the pathophysiology of vasodilation, the physiologic response to the vascular response, and the different drugs used in this situation, focusing on the need to combine early different vasopressors. Fluid loading being insufficient for counteracting vasoplegia, norepinephrine is usually the first-line vasopressor used to restore hemodynamics. Norepinephrine sparing is discussed in further detail through the concomitant use of adrenergic, vasopressinergic, and renin-angiotensin systems and the optimisation of endothelial reactivity with methylene blue. A blueprint for the construction of new studies is outlined to address the question of vasopressor selection and timing in septic shock., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II)., Methods: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation., Results: Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups., Conclusions: This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial., Trial Registration: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015., (© 2023. The Author(s).)

Background: Patients supported on mechanical circulatory support devices experience vasodilatory hypotension due to high surface area exposure to nonbiological and non-endothelialized surfaces. Angiotensin II has been studied in general settings of vasodilatory shock, however concerns exist regarding the use of this vasopressor in patients with pre-existing cardiac failure. The objective of this study was to assess the systemic and central hemodynamic effects of angiotensin II in patients with primary cardiac or respiratory failure requiring treatment with mechanical circulatory support devices. Methods: Multicenter retrospective observational study of adults supported on a mechanical circulatory support device who received angiotensin II for vasodilatory shock. The primary outcome was the intraindividual change from baseline in mean arterial pressure (MAP) and vasopressor dosage after angiotensin II. Results: Fifty patients were included with mechanical circulatory devices that were primarily used for cardiac failure (n = 41) or respiratory failure (n = 9). At angiotensin II initiation, the norepinephrine equivalent vasopressor dosage was 0.44 (0.34, 0.64) and 0.47 (0.33, 0.73) mcg/kg/min in the cardiac and respiratory groups, respectively. In the cardiac group, MAP increased from 60 to 70 mmHg (intraindividual P  < .001) in the 1 h after angiotensin II initiation and the vasopressor dosage declined by 0.04 mcg/kg/min (intraindividual P  < .001). By 12 h, the vasopressor dosage declined by 0.16 mcg/kg/min ( P  = .001). There were no significant changes in cardiac index or mean pulmonary artery pressure throughout the 12 h following angiotensin II. In the respiratory group, similar but nonsignificant effects at 1 h on MAP (61-81 mmHg, P  = .26) and vasopressor dosage (decline by 0.13 mcg/kg/min, P  = .06) were observed. Conclusions: In patients requiring mechanical circulatory support for cardiac failure, angiotensin II produced beneficial systemic hemodynamic effects without negatively impacting cardiac function or pulmonary pressures. The systemic hemodynamic effects in those with respiratory failure were nonsignificant due to limited sample size.

Objectives: To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO)., Design: Single-center retrospective cohort study., Setting: Large academic ECMO center., Patients: Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation., Interventions: None., Measurements and Main Results: Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48-$13.09] vs $1.03 [IQR, $0-$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0-$312.82] vs $0 [IQR, $0-$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286)., Conclusions: Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19., Methods: We performed a retrospective multicenter case-control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020., Results: A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30)  =  0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC]  =  0.55, 95% CI: 0.44-0.65, P value  =  .32; alpha angle [α] AUC  =  0.58, 95% CI: 0.47-0.69, P value  =  .17; K time AUC  =  0.58, 95% CI: 0.46-0.69, P value  =  .67; maximum amplitude (MA) AUC  =  0.54, 95% CI: 0.44-0.64, P value  =  .47; reaction time [R time] AUC  =  0.53, 95% CI: 0.42-0.65, P value  =  .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC  =  0.51, 95% CI: 0.42-0.60, P value  =  .84; R time AUC  =  0.57, 95%CI: 0.48-0.67, P value .07; α AUC  =  0.59, 95%CI: 0.51-0.68, P value  =  .02; K time AUC  =  0.62, 95% CI: 0.53-0.70, P value  =  .07; MA AUC  =  0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events., Conclusions: In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.

Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. In recent times, there is increasing interest in the role of angiotensin II in CS. We sought to systematically review the current literature on the use of angiotensin II in CS., Methods: PubMed, EMBASE, Medline, Web of Science, PubMed Central, and CINAHL databases were systematically searched for studies that evaluated the efficacy of angiotensin II in patients with CS during 01/01/2010-07/07/2022. Outcomes of interest included change in mean arterial pressure (MAP), vasoactive medication requirements (percent change in norepinephrine equivalent [NEE] dose), all-cause mortality, and adverse events., Results: Of the total 2,402 search results, 15 studies comprising 195 patients were included of which 156 (80%) received angiotensin II. Eleven patients (84.6%) in case reports and case series with reported MAP data at hour 12 noted an increase in MAP. Two studies noted a positive hemodynamic response (defined a priori) in eight (88.9%) and five (35.7%) patients. Eight studies reported a reduction in NEE dose at hour 12 after angiotensin II administration and one study noted a 100% reduction in NEE dose. Out of 47 patients with documented information, 13 patients had adverse outcomes which included hepatic injury (2), digital ischemia (1), ischemic optic neuropathy (1), ischemic colitis (2), agitated delirium (1), and thrombotic events (2)., Conclusions: In this first systematic review of angiotensin II in CS, we note the early clinical experience. Angiotensin II was associated with improvements in MAP, decrease in vasopressor requirements, and minimal reported adverse events., Competing Interests: Declaration of Competing Interest PMW previously served as a consultant for La Jolla Pharmaceutical Company., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Disclosure: The authors have no conflicts of interest to report.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is a form of mechanical life support that provides full respiratory bypass in patients with severe respiratory failure as a bridge to recovery or lung transplantation. The use of ECMO for respiratory failure and capable centers offering ECMO has expanded over the years, increasing its availability. As VV-ECMO provides an artificial mechanism for oxygenation and decarboxylation of native blood, it allows for an environment in which safer mechanical ventilatory care may be provided, allowing for treatment and resolution of underlying respiratory pathologies. Landmark clinical trials have provided a framework for better understanding patient selection criteria, resource utilization, and outcomes associated with ECMO when applied in settings of refractory respiratory failure. Maintaining close vigilance and management of complications during ECMO as well as identifying strategies post-ECMO (e.g., recovery, transplantation, etc.), are critical to successful ECMO support. In this review, we examine considerations for candidate selection for VV-ECMO, review the evidence of utilizing VV-ECMO in respiratory failure, and provide practical considerations for managing respiratory ECMO patients, including complication identification and management, as well as assessing for the ability to separate from ECMO support and the procedures for decannulation., (© 2023. The Author(s).)

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25-3.37, p = 0.005, I2 = 0%) and die (OR 1.62, 95% CI 1.19-2.21, p = 0.002, I2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55-6.09, p = 0.33, I2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Objective: To describe the current prescribing practices of direct oral anticoagulants (DOACs) in intensive care unit (ICU) patients and the associated clinical outcomes, including the incidence of major bleeding episodes and the need for intervention (endoscopic, surgical, or interventional radiology guided)., Design: Observational, retrospective chart review., Setting and Participants: Single large academic center study. Participants included patients with critical illness who were admitted to the intensive care units (ICU) at Mayo Clinic from January 1st, 2012, until May 4th, 2018. Adult ICU patients with a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) listed as one of the active medications at the time of hospital admission were included., Results: 37 249 patients in medical and surgical intensive care units were screened for the study period. After excluding patients who did not qualify, 558 unique encounters were included. The median age was 69 (IQR 59-78) years; most patients were male, white Caucasians, and had a median SOFA score of 4. After excluding the patients who had major bleeding episodes in the first 24 hours, 188 (39%) were continued on the same DOAC therapy, 204 (42%) were discontinued without transitioning to another agent, and 95 (20%) were transitioned to another agent. Finally, 410 (84%) were dismissed on DOAC therapy at the end of hospitalization. The difference in the continuation rate of the same DOAC agent beyond 24 hours, discontinuation without transition to an alternate agent, or discontinuation of DOAC with a transition to an alternate anticoagulation agent was not statistically significant ( P  = .60). A total of 52 major bleeding events were identified. Gastrointestinal bleeding was the most common bleeding complication [n (%): 34 (65)], followed by intra-abdominal and peri-procedural bleeding [7 (13.5) and 7 (13.5)]. Thirty-three (65%) patients had a major bleeding complication requiring intervention., Conclusions: Our single-center retrospective study describes the current prescribing practices and preliminary outcomes in ICU patients with prehospital use of DOACs. Up to 20% of the patients were transitioned to a different agent within 24 hours of ICU admission, whereas a significant proportion of patients (42%) had anticoagulation discontinued altogether. Most patients who suffered a major bleeding episode required either endoscopic or surgical intervention to control bleeding., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit (ICU), with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation. As clonidine is an enterally available alpha-2A adrenergic agonist, it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes. The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known. The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms., Aim: To systematically review the practice, dosing schema, and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults., Methods: This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults (≥ 18 years). Randomized controlled trials, prospective cohorts, and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included. The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal. Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use, re-initiation of dexmedetomidine, duration of mechanical ventilation, and ICU length of stay., Results: A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients. All three studies were observational, two being prospective and one retrospective. In all included studies, the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician. Weaning time ranged from 13 to 167 h on average. Enteral clonidine was started in the prospective studies in a similar protocolized method, with 0.3 mg every 6 h. After starting clonidine, patients remained on dexmedetomidine for a median of 1-28 h. Following the termination of dexmedetomidine, two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h, 12h, and 24 h, followed by clonidine discontinuation. For indicators of enteral clonidine withdrawal, the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol. The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation. The re-initiation of dexmedetomidine was not documented in any study. Only 17 (37%) patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies. ICU lengths of stay were similar., Conclusion: Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine. There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021., Data Source: PubMed/MEDLINE., Study Selection: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021., Data Extraction: Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature., Data Synthesis: The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding., Conclusions: This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Sedatives are frequently administered in an ICU and are often dependent on patient population and ICU type. These differences may affect patient-centered outcomes., Objective: Our primary objective was to identify differences in sedation practice among three different ICU types at an academic medical center., Methods: This was a retrospective cross-sectional study of adult patients (≥18 years) requiring a continuous sedative for ≥6 h and admitted to a medical ICU, surgical ICU, and medical/surgical ICU at a single academic medical center in Rochester Minnesota from June 1, 2018 to May 31, 2020. We extracted baseline characteristics; sedative type, dose, and duration; concomitant therapies; and patient outcomes. Summary statistics are presented., Results: A total of 2154 patients met our study criteria (1010 from medical ICU, 539 from surgical ICU, 605 from medical/surgical ICU). Propofol was the most frequently used sedative in all ICU settings (74.1% in medical ICU, 53.8% in surgical ICU, 68.9% in medical/surgical ICU, and 67.5% in all ICUs). The mortality rate was highest in the medical/surgical ICU (40.2% in medical ICU, 26.0% in surgical ICU, 40.7% in medical/surgical ICU, and 36.8% in all ICUs). 90.7% of all patients required mechanical ventilation (92.9% in medical ICU, 88.5% in surgical ICU, and 89.1% in medical/surgical ICU). Overall, patients spent more time in light sedation than deep sedation, 75% versus 10.3%, during their ICU admission. Patients in the medical ICU spent a greater proportion of time positive for delirium than the other ICU settings (35.7% in medical ICU, 9.8% in surgical ICU, and 20% in medical/surgical ICU). Similar amounts of opioids (morphine milligram equivalents) were used during the continuous sedative infusion between the three settings., Conclusions: We observed that patients in the medical ICU spent more time deeply sedated with multiple agents which was associated with a higher proportion of delirium.

Acute kidney injury (AKI) is a syndrome that entails a rapid decline in kidney function with or without injury. The consequences of AKI among acutely ill patients are dire and lead to higher mortality, morbidity, and healthcare cost. To prevent AKI and its short and long-term repercussions, understanding its pathophysiology is essential. Depending on the baseline kidney histology and function reserves, the number of kidney insults, and the intensity of each insult, the clinical presentation of AKI may differ. While many factors are capable of inducing renal injury, they can be categorized into a few processes. The three primary processes reported in the literature are hemodynamic changes, inflammatory reactions, and nephrotoxicity. The majority of patients with AKI will suffer from more than one during their development and/or progression of AKI. Moreover, the development of one usually leads to the instigation of another. Thus, the interactions and progression between these mechanisms may determine the severity and duration of the AKI. Other factors such as organ crosstalk and how our concurrent therapies interact with these mechanisms complicate the pathophysiology of the progression of the AKI even further. In this narrative review article, we describe these three main pathophysiological processes that lead to the development and progression of AKI. © 2022 American Physiological Society. Compr Physiol 12: 1-14, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

Objective: The primary aim of this study was to identify predictors of response to hydroxocobalamin., Design: A retrospective cohort study., Setting: A single large academic medical center within the cardiovascular surgery intensive care unit., Participants: Postoperative cardiovascular surgery patients within 96 hours of cardiopulmonary bypass separation between May 7, 2018, and August 1, 2020., Interventions: None., Measurements and Main Results: Of the 66 administrations, 43 administrations yielded hemodynamic improvements (65.2%). Comparing responders to nonresponders, nonresponders had a greater median cardiopulmonary bypass duration (223 v 131 minutes; p < 0.001) and a prolonged median cross-clamp time (153 v 77 minutes; p = 0.014). Multivariate modeling demonstrated a reduction in the odds of being a responder by 57% for every 60 minutes of cardiopulmonary bypass duration (odds ratio, 0.43; 95% confidence interval, 0.28-0.68; p < 0.001), but there was no significant difference based on time from intensive care unit admission to hydroxocobalamin administration (odds ratio, 0.95; 95% confidence interval, 0.88-1.03; p = 0.20)., Conclusion: Shorter total bypass duration and more rapid utilization after bypass of hydroxocobalamin were associated with a higher likelihood of response to refractory vasoplegic shock., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: PMW has previously served as a consultant for La Jolla Pharmaceutical Company. All other authors have no relevant disclosures.