Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Asystole Following Concomitant Intravenous Administration of Neostigmine and Dexmedetomidine in a Patient With Acute Colonic Pseudo-Obstruction.

Acute colonic pseudo-obstruction (ACPO) is a condition characterized by acute dilation of the large bowel without evidence of mechanical obstruction that occurs in a variety of hospitalized patients with many predisposing factors. Management includes supportive care and limitation of offending medications with mainstays of treatment of neostigmine administration and colonic decompression. We report the case of a critically ill patient with ACPO who experienced bradycardia and a brief episode of asystole when receiving concomitant dexmedetomidine and neostigmine infusions but who later remained hemodynamically stable when receiving propofol and neostigmine infusions. The bradycardia and associated hemodynamic instability experienced while on dexmedetomidine and neostigmine infusions were rapidly corrected with atropine and cessation of offending agents. Because ACPO is encountered frequently and the use of dexmedetomidine as a sedative agent in the ICU is increasing, practitioners should be aware of the additive risk of bradycardia and potential for asystole with the combination of neostigmine and dexmedetomidine. Electronic drug interaction databases should be updated and drug information sources should include a drug-drug interaction between dexmedetomidine and neostigmine to reduce the likelihood of concomitant administration.

Effectiveness and Safety of Twice- Versus Thrice-Daily Subcutaneous Heparin for Venous Thromboembolism Prophylaxis at a Large Academic Medical Center.

BACKGROUND: Dosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP). OBJECTIVE: The purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP. METHODS: A single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310). CONCLUSION AND RELEVANCE: There was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.

Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Weighing ≥ 120 Kilograms versus 60-120 Kilograms.

BACKGROUND: Direct oral anticoagulants (DOACs) have become favorable choices for anticoagulation due to their fixed-dose schedule, limited need for monitoring, and non-inferiority or superiority to warfarin. DOACs are currently not recommended in patients with a body weight ≥ 120 kg or body mass index ≥ 40 kg/m2 due to limited data regarding safety and efficacy. OBJECTIVE: The aim of this study was to compare the safety and efficacy of DOACs in patients with nonvalvular atrial fibrillation (NVAF) and weighing ≥ 120 kg with those weighing < 120 kg. METHODS: A single-center, retrospective study was conducted in patients weighing ≥ 120 kg who received either apixaban, dabigatran, or rivaroxaban for stroke risk reduction in NVAF, and matched to patients who weighed < 120 kg. The primary outcome was the incidence of stroke, deep vein thrombosis, pulmonary embolism, or myocardial infarction, while the safety outcome was the incidence of major or clinically relevant non-major bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 318 patients weighing ≥ 120 kg with NVAF and meeting the inclusion criteria were evaluated and matched with 318 patients weighing < 120 kg. The primary outcome occurred in 2.5% of patients in the ≥ 120 kg group and in 3.1% of patients in the < 120 kg group (p = 0.632). The safety outcome occurred in 5.3% and 6.6% of patients in these respective groups (p = 0.503). CONCLUSION: Apixaban, dabigatran, or rivaroxaban may be well-tolerated and effective anticoagulant options in patients with NVAF weighing ≥ 120 kg.

Major publications in the critical care pharmacotherapy literature: 2019.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2019. MATERIALS AND METHODS: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 36 journals monthly for impactful articles and reviewed 113 articles during 2019 according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. RESULTS: Articles with a 1A grade, including three clinical practice guidelines, six meta-analyses, and five original research trials are reviewed here from those included in the monthly CCPLU. Clinical practice guidelines on the use of polymyxins and antiarrhythmic drugs in cardiac arrest as well as meta-analyses on antipsychotic use in delirium, stress ulcer prophylaxis (SUP), and vasoactive medications in septic shock and cardiac arrest were summarized. Original research trials evaluated delirium, sedation, neuromuscular blockade, SUP, anticoagulation reversal, and hemostasis. CONCLUSION: This clinical review and expert opinion provides summary and perspectives of clinical practice impact on influential critical care pharmacotherapy publications in 2019.