Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

International Survey of Thrombolytic Use for Treatment of Cardiac Arrest Due to Massive Pulmonary Embolism.

OBJECTIVES: This survey sought to characterize the national prescribing patterns and barriers to the use of thrombolytic agents in the treatment of pulmonary embolism, with a specific focus on treatment during actual or imminent cardiac arrest. DESIGN: A 19-question international, cross-sectional survey on thrombolytic use in pulmonary embolism was developed, validated, and administered. A multivariable logistic regression was conducted to determine factors predictive of utilization of thrombolytics in the setting of cardiac arrest secondary to pulmonary embolism. SETTING: International survey study. SUBJECTS: Physicians, pharmacists, nurses, and other healthcare professionals who were members of the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thrombolytic users were compared with nonusers. Respondents (n = 272) predominately were physicians (62.1%) or pharmacists (30.5%) practicing in an academic medical center (54.8%) or community teaching setting (24.6%). Thrombolytic users (n = 177; 66.8%) were compared with nonusers (n = 88; 33.2%) Thrombolytic users were more likely to work in pulmonary/critical care (80.2% thrombolytic use vs 59.8%; p < 0.01) and emergency medicine (6.8% vs 3.5%; p < 0.01). Users were more likely to have an institutional guideline or policy in place pertaining to the use of thrombolytics in cardiac arrest (27.8% vs 13.6%; p < 0.01) or have a pulmonary embolism response team (38.6% vs 19.3%; p < 0.01). Lack of evidence supporting use and the risk of adverse outcomes were barriers to thrombolytic use. Working in a pulmonary/critical care environment (odds ratio, 2.36; 95% CI, 1.24-4.52) and comfort level (odds ratio, 2.77; 95% CI, 1.7-4.53) were predictive of thrombolytic use in the multivariable analysis. CONCLUSIONS: Most survey respondents used thrombolytics in the setting of cardiac arrest secondary to known or suspected pulmonary embolism. This survey study adds important data to the literature surrounding thrombolytics for pulmonary embolism as it describes thrombolytic user characteristic, barriers to use, and common prescribing practices internationally.

Medication-Induced Hyperlactatemia and Lactic Acidosis: A Systematic Review of the Literature.

Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations.

Using lean methodology to optimize time to antibiotic administration in patients with sepsis.

PURPOSE: Results of a study to apply lean methodology to an inpatient pharmacy workflow to optimize timely administration of Centers for Medicare and Medicaid Services (CMS)-approved antibiotics for patients with severe sepsis or septic shock are presented. METHODS: This quasi-experimental study was conducted at an 802-bed institution using lean methodology to assess the inpatient pharmacy workflow for dispensing antibiotics to adult patients. The preintervention and postintervention phases occurred from February to September, 2015, and from October 2015 to May 2016, respectively. Patients were included if they were hospitalized with an intensive care department 9 or 10 code for severe sepsis or septic shock, had an order for a CMS-approved antibiotic, and met clinical criteria for severe sepsis or septic shock. Patients were excluded if they received first-dose antibiotics in the emergency department. The primary outcome was time from CMS-approved antibiotic order entry to medication administration. Secondary outcomes included timeliness of individual workflow dispensing parameters, patient outcomes, and compliance with the newly implemented workflow. RESULTS: A total of 102 patients were included, 54 in the preintervention and 48 in the postintervention group. Baseline demographics between the groups were similar. There was a significant reduction in the median time from order entry to antibiotic administration by 40 minutes (preintervention phase 120 minutes versus postintervention phase 80 minutes, p = 0.014). Time from order verification to administration was significantly reduced. There was no difference in other secondary outcomes. CONCLUSION: Lean methodology was successfully used to reduce time to antibiotic administration, which led to improved compliance with the newly implemented sepsis CMS core measure.

Major publications in the critical care pharmacotherapy literature in 2015.

PURPOSE: Recently published practice guidelines and research reports on pharmacotherapy in critical care patient populations are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group is composed of over 50 experienced critical care pharmacists who evaluate 31 peer-reviewed journals monthly to identify literature pertaining to pharmacotherapy in critical care populations. Articles are chosen for summarization in a monthly CCPLU Group publication on the basis of applicability and relevance to clinical practice and strength of study design. From January to December 2015, a total of 121 articles were summarized; of these, 3 articles presenting clinical practice guidelines and 12 articles presenting original research findings were objectively selected for inclusion in this review based on their potential to change or reinforce current evidence-based practice. The reviewed guidelines address the management of intracranial hemorrhage (ICH), adult advanced cardiac life support (ACLS) and post-cardiac arrest care, and the management of supraventricular tachycardia (SVT). The reviewed research reports address topics such as nutrition in critically ill adults, administration of ß-lactams for severe sepsis, anticoagulant selection in the context of continuous renal replacement therapy, early goal-directed therapy in septic shock, magnesium use for neuroprotection in acute stroke, and progesterone use in patients with traumatic brain injury. CONCLUSION: Important recent additions to the critical care pharmacy literature include updated joint clinical practice guidelines on the management of spontaneous ICH, ACLS, and SVT.

Inhaled Iloprost for Chronic Thromboembolic Pulmonary Hypertension (CTEPH) During Pregnancy: A Case Report.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subset of pulmonary hypertension caused by acute and recurrent pulmonary emboli. Pulmonary thromboendarterectomy is the treatment of choice, but 10-50% of patients are ineligible for this procedure. We describe the case of a 25-year-old, morbidly obese (228-kg, body mass index 83.5 kg/m(2) ) pregnant woman (G3 P2 ) who presented at 24 weeks' gestation; bilateral pulmonary angiography revealed filling defects and confirmed the diagnosis of CTEPH. The patient was evaluated and deemed to present too high of a risk for pulmonary thromboendarterectomy, so a multidisciplinary team initiated medical therapy. Sildenafil 20 mg orally 3 times/day was started at week 24 of gestation, and inhaled iloprost was added at 26 weeks and titrated to 5 µg inhaled every 2 hrs in order to optimize hemodynamic status prior to a cesarean section delivery scheduled to be performed 6 weeks later. At 32 weeks of gestation, the patient's pulmonary arterial systolic pressure was 77 mm Hg, right atrial pressure was 15 mm Hg, and pulmonary capillary wedge pressure of 16 mm Hg, and a healthy 1741-g male infant was delivered by cesarean section. The patient was transferred back to the medical intensive care unit in stable condition and discharged home 9 days following the procedure. Pharmacotherapeutic strategies for patients with CTEPH who become pregnant are limited to phosphodiesterase type 5 inhibitors and prostacyclin analog therapies due to the teratogenicity of the other drug classes used to treat the disorder (endothelin receptor antagonists and soluble guanylate cyclase stimulators). To our knowledge, this is the first case report of inhaled iloprost use in addition to oral sildenafil to improve patient symptomatology and hemodynamics during the peripartum period of a young pregnant patient with inoperable CTEPH. This drug therapy was used safely, with no noted adverse effects to the newborn or to the patient.

Application of a pull on a disk method to measure surface tension of liquids.

The intrinsic property of liquids is a vital indicator of formulation performance and stability. Therefore, investigation of the interfacial phenomenon of surface tension is a routine procedure in the development of products in a wide variety of areas including foods, pharmaceuticals, cosmetics, and painting technologies. We hypothesize that studies related to the maximum pull on a rod can be extrapolated to disk geometry and applied to measure surface tension using a texture analyzer. A glass disk probe was attached to the arm of a texture analyzer and pulled from the liquid surface. The maximum force of detachment was used to calculate surface tension extrapolating from the theory of maximum pull on a rod. The surface tension of water, ethanol, and a hydroalcoholic solution was measured and compared with literature values to validate this hypothesis. The calculated values of surface tension for the liquids studied were within 5% of the reported values. Probe diameter appears to have an important role on surface tension accuracy compared with literature values. Slight discrepancies can be attributed to temperature control and leveling of liquid surface, although still in accordance with the reported values of surface tension measured using different methods. This study presents a simple, precise, and quick method to determine the surface tension of liquids from the maximum pull on a disk. Further studies are warranted to determine the optimum glass disk probe diameter for better accuracy.