Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin. DESIGN: A retrospective cohort study. SETTING: At a single-center, large academic medical center. PARTICIPANTS: One hundred thirty-six critically ill patients. INTERVENTIONS: The following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL. MEASUREMENTS AND MAIN RESULTS: Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001). CONCLUSION: Anticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

Impact of a Real-Time, Pharmacist-Led, Intensive Care Unit-Based Feedback Intervention on Analgesia and Sedation Quality Among Mechanically Ventilated Patients.

BACKGROUND: Consensus guidelines for pain, agitation, and delirium (PAD) in mechanically ventilated patients recommend maintaining a light level of sedation. LOCAL PROBLEM: Consistent attainment of target PAD assessments in mechanically ventilated ICU patients is often challenging. METHODS: This is a single-center, prospective study. INTERVENTIONS: In the intervention group, a pharmacist provided weekly feedback to nurses on their success in achieving target PAD assessments compared with a historical cohort without feedback. RESULTS: Overall, 478 patients and 205 nurses were included. The odds of having weekly Richmond Agitation-Sedation Scale (RASS) score, pain score goals, and Confusion Assessment Method for the ICU (CAM-ICU) negative assessments at goal between the intervention and control groups fluctuated over time without a discernible trend. CONCLUSION: The provision of weekly feedback to nurses on PAD nursing assessments by a pharmacist did not impact the achievement of PAD goals among critically ill mechanically ventilated patients.

Medication Histories in Critically Ill Patients Completed by Pharmacy Personnel.

BACKGROUND: Although critically ill adults often have extended hospital lengths of stay and are at high risk of having medication-related adverse events, the value of medication histories in these patients remains underreported. OBJECTIVE: To assess the feasibility of performing medication histories in critically ill adults and to establish the frequency of and characterize identified discrepancies. METHODS: This prospective study included patients admitted to 4 intensive care units (ICUs) in a large academic medical center and was conducted in 2 phases. In phase 1, medication histories were conducted over a 5-week period by clinical pharmacists to assess feasibility. In phase 2, medication histories were conducted over a 3-week period by a pharmacy technician. Medication discrepancies, defined as any difference between the documented and pharmacy personnel-identified home medication list, were aggregated in both phases and adjudicated for severity. RESULTS: In phase 1, 127 medication histories were completed (42.3% of admitted patients). Impaired cognition was the most common barrier encountered; however, 76% of patients were able to have a history completed if an attempt was made. In phase 2, a medication history was completed for 176 patients (58.9% of admitted patients). In aggregate, 1155 discrepancies were identified, with 78.2% of patients having a discrepancy. The median number of discrepancies per patient was 3 (interquartile range = 1-5); 11 life-threatening, 101 serious, and 326 significant discrepancies were identified. Conclusion and Relevance: A pharmacy personnel-based medication history program in the ICU is feasible and assists in the discovery of medication discrepancies with the potential for patient harm.

Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists?

Chemotherapy-induced nausea and vomiting is one of the most concerning adverse drug effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20-30 % of patients experience breakthrough nausea and vomiting secondary to chemotherapy. To assess the variability of 5-hydroxytryptamine type 3 receptor antagonist efficacy caused by genetic variation, a review of the available literature was conducted. From the literature, three sources of pharmacogenomic variability were identified: polymorphisms associated with 5-hydroxytryptamine type 3 receptor subunits, drug metabolism via cytochromes P450, and drug transport in the body. Testing for receptor subunit polymorphisms is not applicable to a clinical setting at this time; however, cytochrome P450 2D6 testing is FDA-approved and widely accessible. Cytochrome P450 2D6 ultrarapid metabolizers and poor metabolizers displayed altered antiemetic efficacy when compared with intermediate metabolizers and extensive metabolizers. We postulate that testing for cytochrome P450 2D6 phenotypes may be the most accessible way to provide individualized antiemetic therapy in the future.