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.

Advances in remote and cloud-based simulation through web conferencing platforms.

INTRODUCTION: Simulation-based learning has become an essential element in entry-level perfusion education. While the use of simulation has been demonstrated to improve patient outcomes, few institutions possess the budgetary resources to build and maintain a high-fidelity simulation environment. This project aims to identify novel uses of web conferencing platforms to support in-person, remote, and virtual simulation exercises. METHODS: The Zoom Virtual Meeting platform (Zoom Video Communications, Inc.) was incorporated into the perfusion simulation curriculum at the Medical University of South Carolina CVP Program. Among the observed benefits of incorporating meeting platform software included high-definition audio/visual outputs and recording capabilities, 3-D remote simulation, remote simulation proctoring, and classroom-based learning. Additional Zoom features included remote controlled screen access and sharing, annotations, and break-out rooms and activities. CONCLUSION: The combination of high-fidelity simulation with virtual and remote features may enhance the learning experience in healthcare education. Future developments in technology and software, simulation education, and instructions through virtual/remote learning may provide a pathway for the future of cardiovascular perfusion education.

Opioid and Benzodiazepine Requirements in Obese Adult Patients Receiving Extracorporeal Membrane Oxygenation.

Background: The use of extracorporeal membrane oxygenation (ECMO) sometimes requires deep levels of sedation (Richmond Agitation Sedation Scale [RASS] -5) in patients with acute respiratory distress syndrome (ARDS). The role of obesity in opioid and sedative requirements remains unclear in patients receiving ECMO. Objective: This study sought to determine whether obesity increases midazolam and opioid requirements in patients receiving venovenous (vv)-ECMO up to the first 7 days after initiation. Methods: This was a retrospective cohort study of adult patients with ARDS managed with vv-ECMO. Results: The obese (n = 38) and nonobese (n = 43) groups had similar baseline characteristics. Fentanyl equivalents were significantly higher on day 3 in the obese group (P = 0.02) despite similar RASS scores with no differences in midazolam requirements. There were no differences in duration of ECMO, length of stay, or mortality. Conclusion and Relevance: Daily midazolam requirements were not significantly different, and opioid requirements were only significantly higher in the obese group on day 3 despite similar levels of sedation. The impact of obesity with the addition of ECMO and how to adapt doses of medications remains elusive.

Practices surrounding antimicrobial use in patients managed with extracorporeal membrane oxygenation: An international survey.

PURPOSE: This study aimed to survey critical care clinicians and characterize their perception of antimicrobial dosing strategies in patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: International, cross-sectional survey distributed to members of the Society of Critical Care Medicine in October 2022. RESULTS: Respondents were primarily physicians (45%), with 92% practicing in North America. Ninety-seven percent of respondents reported antimicrobial dosing in critically ill patients to be challenging, due to physiological derangements seen in the patient population. Eighty-seven percent reported consideration of physicochemical drug properties when dosing antimicrobials in ECMO-supported patients, with lipophilicity (83%) and degree of protein binding (74%) being the two most common. Respondents' approach to antimicrobial dosing strategies did not significantly differ in critically ill ECMO-supported patients, compared to patients with equal severity of illness not receiving ECMO support. CONCLUSION: Approaches to antimicrobial dosing strategies do not significantly differ among respondents between critically ill patients on ECMO support, compared to patients with equal severity of illness not receiving ECMO support. These findings were unexpected considering the added physiologic complexity of the ECMO circuit to critically ill adult patients and the need for well designed and adequately powered studies to inform empiric dosing guidance for ECMO-supported patients.

Use of N-Acetylcysteine for Clozapine-Induced Acute Liver Injury: A Case Report and Literature Review.

Purpose: To report a case of clozapine-induced hepatotoxicity managed with intravenous (IV) N-acetylcysteine (NAC) and summarize the available literature. Summary: A 46-year-old woman with history of bipolar disorder with psychotic features presented to the intensive care unit with asterixis and elevations in liver enzymes. The patient had been initiated on risperidone, clozapine, and lithium approximately 1 month prior to admission. After ruling out other possible non-drug etiologies, clozapine was suspected as the likeliest cause of the acute liver injury. Her acute liver injury was managed with the discontinuation of all antipsychotics, administration of IV NAC, and other standard of care supportive measures. Conclusion: Although clozapine has been associated with hepatitis and acute liver failure, there are no reports of NAC used in the management of clozapine-induced hepatotoxicity. NAC was used in our patient after considering the potential benefit and limited adverse effects. The role of NAC in non-acetaminophen-induced acute liver failure remains promising, but more research is warranted.

Procalcitonin in special patient populations: Guidance for antimicrobial therapy.

PURPOSE: Procalcitonin (PCT) is an endogenous hormone that increases reliably in response to bacterial infection, and measurement of serum PCT levels is recommended to help guide antimicrobial therapy. The utility of PCT assessment in special patient populations (eg, patients with renal dysfunction, cardiac compromise, or immunocompromised states and those undergoing acute care surgery) is less clear. The evidence for PCT-guided antimicrobial therapy in special populations is reviewed. SUMMARY: In the presence of bacterial infection, nonneuroendocrine PCT is produced in response to bacterial toxins and inflammatory cytokines, resulting in markedly elevated levels of serum PCT. Cytokine induction in nonbacterial inflammatory processes activated by acute care surgery may alter the interpretation of PCT levels. The reliability of PCT assessment has also been questioned in patients with renal dysfunction, cardiac compromise, or immunosuppression. In many special populations, serum PCT may be elevated at baseline and increase further in the presence of infection; thus, higher thresholds for diagnosing infection or de-escalating therapy should be considered, although the optimal threshold to use in a specific population is unclear. Procalcitonin-guided antimicrobial therapy may be recommended in certain clinical situations. CONCLUSION: Procalcitonin may be a reliable marker of infection even in special populations with baseline elevations in serum PCT. However, due to unclear threshold values and the limited inclusion of special populations in relevant clinical trials, PCT levels should be considered along with clinical criteria, and antibiotics should never be initiated or withheld based on PCT values alone. Procalcitonin measurement may have a role in guiding de-escalation of antibiotic therapy in special populations; however, the clinician should be aware of disease states and concomitant therapies that may affect interpretation of results.

Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID-19.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork-Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.

Ventilatory and Pharmacotherapeutic Strategies for Management of Adult Patients on Extracorporeal Life Support.

Extracorporeal life support (ECLS) can provide mechanical support for patients with severe life-threatening cardiac or respiratory failure. ECLS is a complex therapy that has increased in use over several decades owing to advances in technology. In concert with this growth, there is an increased need to understand the complexity of this technology to augment the effectiveness of ECLS and minimize complications such as ventilator-induced lung injury, bleeding, thrombosis, infections, and inadequate drug dosing. The purpose of this review was to discuss management strategies in adult patients receiving ECLS and provide recommendations on ventilator management, provision of adequate analgesia and sedation, treatment and prevention of infections, and anticoagulation.

Moderate to Severe Acute Respiratory Distress Syndrome Management Strategies: A Narrative Review.

Acute respiratory distress syndrome (ARDS) remains a common complication associated with significant negative outcomes in critically ill patients. Lung-protective mechanical ventilation strategies remain the cornerstone in the management of ARDS. Several therapeutic options are currently available including fluid management, neuromuscular blocking agents, prone positioning, extracorporeal membrane oxygenation, corticosteroids, and inhaled pulmonary vasodilating agents (prostacyclins and nitric oxide). Unfortunately, an evidence-based, standard-of-care approach in managing ARDS beyond lung-protective ventilation remains elusive, contributing to significant variability in clinical practice. Although the optimal therapeutic strategy for managing moderate to severe ARDS remains extremely controversial, therapies supported with more robust clinical evidence should be considered first. The purpose of this narrative review is to discuss the published clinical evidence for both pharmacologic and nonpharmacologic management strategies in adult patients with moderate to severe ARDS as well as to discuss practical considerations for implementation.

Current practice and perceptions regarding pain, agitation and delirium management in patients receiving venovenous extracorporeal membrane oxygenation.

PURPOSE: To characterize monitoring of pain, agitation, and delirium; investigate opioid and sedative choices; and describe prevention and treatment of delirium in adults receiving venovenous extracorporeal membrane oxygenation (vv-ECMO) for respiratory failure. MATERIALS AND METHODS: International, cross-sectional survey distributed January 2018 to members of the Society of Critical Care Medicine. RESULTS: Respondents were predominately physicians (58%) from North America (89%). Fentanyl (77%) and hydromorphone (48%) were the most common intravenous opioids used to manage pain. A deep level of sedation was targeted in the first 24-h after initiation of vv-ECMO 64% of the time. When deep sedation was targeted, propofol (70%) and benzodiazepines (41%) were the most common sedatives. The most common sedatives for light sedation were dexmedetomidine (45%) and propofol (39%). Delirium prevention included avoidance of benzodiazepines (73%), whereas the most common treatment strategy was scheduled atypical antipsychotics (83%). Centers that extubated patients during vv-ECMO used dexmedetomidine as the second preferred sedative as compared to benzodiazepines at non-extubating centers (p = 0.04). CONCLUSIONS: Most respondents use validated scales and protocols to assess and manage pain, agitation/sedation, and delirium. The majority of respondents reported targeting a deep level of sedation with propofol being used for both deep and light levels of sedation.

Severe Thrombocytopenia in Adults with Severe Acute Respiratory Distress Syndrome: Impact of Extracorporeal Membrane Oxygenation Use.

Extracorporeal membrane oxygenation (ECMO) use is perceived to cause thrombocytopenia (T), but the role of non-ECMO factors in the development of T remains unclear. We sought to evaluate the incidence and factors associated with severe T (platelet count ≤ 50,000/µl) in adults with severe acute respiratory distress syndrome (ARDS) managed with or without ECMO. The ECMO (n = 32) versus the non-ECMO (n = 53) groups had a similar baseline platelet count (214,000 vs. 179,000/µl), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.13), unfractionated heparin (UFH) exposure (p = 0.62), and severe T incidence (25 vs. 19%, p = 0.5). Although the APACHE II score (p = 0.01), presence of liver failure (p = 0.08), and platelet transfusion (p = 0.0009) were different between the severe T (18/85 [21%]) and non-severe T groups (67/85 [79%]), the incidence of septic shock (p = 0.64), heparin infusion use (p = 0.41), exposure to non-heparin T-causing medications (p = 0.77) and ECMO use (p = 0.5) were not. An adjusted multivariate linear regression model revealed that only the APACHE II score was independently associated with the development of severe T (p = 0.01) but use of ECMO was not (p = 0.32) ECMO use may not affect the incidence of severe T among adults with severe ARDS. Larger studies that are prospective in nature are required to confirm this finding.

Effect of Extracorporeal Membrane Oxygenation Use on Sedative Requirements in Patients with Severe Acute Respiratory Distress Syndrome.

STUDY OBJECTIVES: To compare sedative dose requirements during the 6-hour period when they are greatest in patients with severe acute respiratory distress syndrome (ARDS), as well as the time from severe ARDS onset to reach this maximum sedation exposure, between patients with severe ARDS who were managed either with or without extracorporeal membrane oxygenation (ECMO). Also, to explore factors other than ECMO use that may influence sedation requirements during this period of maximum sedation. DESIGN: Retrospective comparative cohort analysis. DATA SOURCES: Two academic centers, one with an adult ECMO program and one without. PATIENTS: Consecutive adults with severe ARDS who were receiving continuous-infusion sedative therapy for at least 48 hours from the time of severe ARDS diagnosis and who were managed with ECMO (34 patients) or without ECMO (60 patients) between 2009 and 2013. MEASUREMENTS AND MAIN RESULTS: Among patients managed with ECMO, the maximum median (interquartile range [IQR]) 6-hr sedative exposure (in midazolam equivalents) was nearly twice as high (118 [IQR 48-225] mg vs 60 [37-99] mg, p=0.004) and was reached, on average, 3 days later (4 [IQR 1-8] vs 1 [IQR 0.5-6] days, p=0.003) than patients not managed with ECMO. Patients managed with ECMO were younger, had a higher Sequential Organ Failure Assessment score, and, in the 24 hours prior to the period of maximum sedative exposure, had a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and were more likely to receive renal replacement and high-dose fentanyl (2000 µg or more/24 hrs) therapy. An adjusted multivariable linear regression model using the natural logarithmic value of the maximum sedative exposure in a 6-hour period revealed that patient age (p=0.04) and administration of high-dose fentanyl in the 24 hours prior to the 6-hour period of maximum sedative use (p<0.0001) were each independently associated with the maximum 6-hour sedative requirement reached, but the use of ECMO was not (p=0.52). CONCLUSION: Although the application of ECMO during severe ARDS resulted in a period of maximum sedation exposure that was both greater and took longer to reach, factors other than ECMO, particularly high-dose opioid administration, appeared more likely to account for this maximum sedation use. Further research surrounding sedative requirements, clearance, and patient response during ECMO is required.

Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.

PURPOSE: Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH). MATERIALS AND METHODS: We conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH. RESULTS: There were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin-platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69×10(9)/L (22-126×10(9)/L) vs 87.5×10(9)/L (63-149×10(9)/L); P=.04. The lowest platelet count on the day of HIT testing was 43×10(9)/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT. CONCLUSIONS: The evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin-platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure.