Eli N. Deal

Implementation of a real-time computerized sepsis alert in nonintensive care unit patients*

Objective:Early therapy of sepsis involving fluid resuscitation and antibiotic administration has been shown to improve patient outcomes. A proactive tool to identify patients at risk for developing sepsis may decrease time to interventions and improve patient outcomes. The objective of this study was to evaluate whether the implementation of an automated sepsis screening and alert system facilitated early appropriate interventions. Design:Prospective, observational, pilot study. Setting:Six medicine wards in Barnes-Jewish Hospital, a 1250-bed academic medical center. Patients:Patients identified by the sepsis screen while admitted to a medicine ward were included in the study. A total of 300 consecutive patients were identified comprising the nonintervention group (n = 200) and the intervention group (n = 100). Interventions:A real-time sepsis alert was implemented for the intervention group, which notified the charge nurse on the patients hospital ward by text page. Measurements and Main Results:Within 12 hrs of the sepsis alert, interventions by the treating physicians were assessed, including new or escalated antibiotics, intravenous fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After exclusion of patients without commitment to aggressive management, 181 patients in the nonintervention group and 89 patients in the intervention group were analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the intervention group had received ≥1 intervention vs. 55.8% in the nonintervention group (p = .018). Antibiotic escalation, intravenous fluid administration, oxygen therapy, and diagnostic tests were all increased in the intervention group. This was a single-center, institution- and patient-specific algorithm. Conclusions:The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for sepsis.

Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients

Obesity increases the risk for venous thromboembolism (VTE), but whether high-dose thromboprophylaxis is safe and effective in morbidly obese inpatients is unknown. It was the objective of this study to quantify the efficacy and safety of high-dose thromboprophylaxis with heparin or enoxaparin in inpatients with weight > 100 kilograms (kg) within the BJC HealthCare system. Ina retrospective cohort study, we analysed 9,241 inpatients with weight > 100 kg discharged from three hospitals in the BJC HealthCare system from 2010 through 2012. We compared the incidence of VTE in patients who received high-dose thromboprophylaxis (heparin 7,500 units three times daily or enoxaparin 40 mg twice daily) to those who received standard doses (heparin 5,000 units two or three times daily or enoxaparin 40 mg once daily). The primary efficacy outcome was hospital-acquired VTE identified by International Classification of Diseases (ICD)-9 diagnosis codes. The primary safety outcome was bleeding events identified by ICD-9 codes. Among the 3,928 morbidly obese inpatients (weight > 100 kg and body mass index [BMI] ≥ 40 kg/m²), high-dose thromboprophylaxis approximately halved the odds of symptomatic VTE (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.27-1.00; p = 0.050). The rate of VTE was 1.48% (35/2,369) in these morbidly obese inpatients who received standard doses of thromboprophylaxis, compared to 0.77% (12/1,559) in those who received high doses. High-dose thromboprophylaxis did not increase bleeding (OR 0.84, 95% CI 0.66-1.07, p = 0.15). Independent predictors of VTE were surgery, male sex, cancer, and BMI. In conclusion, high-dose thromboprophylaxis nearly halves the rate of VTE in morbidly obese inpatients.

Comparison of Bivalirudin and Argatroban for the Management of Heparin-Induced Thrombocytopenia

Study Objectives. To compare the effectiveness of bivalirudin and argatroban in achieving anticoagulation goals and to compare clinical outcomes assessing the safety and efficacy in patients with known or suspected heparin‐induced thrombocytopenia (HIT).

Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients.

Background: Most literature available for unfractionated heparin (UFH) supports the use of actual body weight for dosing all patients, yet a small proportion of the patients in these studies were morbidly obese. The most appropriate dosing strategy for therapeutic UFH in this patient population is not clearly defined. Objective: To better define appropriate UFH dosing strategies in morbidly obese patients and to evaluate the safety of a weight-based heparin nomogram in this patient population. Methods: Patients with class III (morbid) obesity receiving therapeutic doses of a UFH infusion for greater than 24 hours were evaluated. Two comparator groups of overweight/class I–II obesity and normal/underweight patients were created by matching patients to the class III obesity group. Doses and times to therapeutic activated partial thromboplastin time (aPTT), bleeding rates, and mortality were assessed. Results: The mean infusion rate required to obtain a first therapeutic aPTT was 11.5 units/kg/h in the class III obesity group (n = 94) versus 12.5 units/kgm and 13.5 units/kg/h for the overweight/class I–II obesity (n = 92) and normal/underweight (n = 87) groups, respectively (p = 0.001). The mean times to a first therapeutic aPTT were 21.3, 22.1, and 29.9 hours, respectively (p = 0.421). There was a statistically significant difference in the infusion rate required to obtain 2 consecutive therapeutic aPTTs between groups (p = 0.016), with higher weight groups requiring smaller (per kilogram actual body weight) infusion rates, but there was no significant difference in the time to reach 2 consecutive therapeutic aPTTs (p = 0.776). There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups. Conclusions: Morbidly obese patients require smaller UFH infusion rates per kilogram actual body weight compared to patients with lower body mass indices. UFH dosing recommendations should be modified to reflect body mass index classification.

Role of corticosteroids in the management of acute respiratory distress syndrome

BACKGROUND Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. OBJECTIVE The aim of this review was to evaluate randomized, controlled trials describing the role of corticosteroids in preventing and treating ARDS. METHODS English-language randomized, controlled trials were identified using MEDLINE via PubMed and EMBASE searches (key terms: acute respiratory distress syndrome, acute lung injury, and corticosteroids; years: 1968-January 2008). RESULTS A total of 10 trials were found and included in this analysis. Trials describing the role of high-dose corticosteroids compared with controls in preventing ARDS found no benefit, with the range of occurrence of ARDS in at-risk populations from 14% to 64% and absolute increases in mortality from 4% to 31%. Conflicting evidence was found for treating late-phase ARDS with corticosteroids, with 13% hospital mortality among patients receiving corticosteroids versus 63% with controls (P = 0.03) in one small study, but no significant difference was found when evaluating 60-day mortality (corticosteroid group, 29.2% vs control, 28.6%) in another investigation. The use of high-dose corticosteroids for the treatment of early phase ARDS was not associated with significant differences in 45-day mortality (methylprednisolone, 60% vs control, 63%). However, one trial found that methylprednisolone taper for early ARDS was associated with significant improvement in lung function or extubation (69.8% vs 35.7%; P = 0.002), fewer days on mechanical ventilation (median, 5.0 vs 9.5; P = 0.002), higher intensive care unit survival (79.4% vs 57.4%; P = 0.03), but similar rates of hospital survival (methylprednisolone, 76.2% vs control, 57.1%; P = NS). CONCLUSIONS Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\2-14) ARDS, but this evidence is controversial.

Predictors of In‐Hospital Mortality for Bloodstream Infections Caused by Enterobacter Species or Citrobacter freundii

Study Objective. To identify predictors of in‐hospital mortality among patients with bacteremia caused by Enterobacter cloacae, Enterobacter aerogenes, or Citrobacter freundii.

Inpatient insulin orders: Are patients getting what is prescribed?†

BACKGROUND In-hospital insulin administration is associated with many medication errors, but the frequency and reasons for insulin administration errors are poorly described. To document types and frequency of errors related to insulin administration, an examination of 4 units was conducted. METHODS Using snapshot methodology, 4 non-intensive care unit (ICU) areas (medicine, cardiology, transplant, and surgery) were examined in an observational, prospective manner for 4 weeks. Each patient on insulin on the first day was followed for 7 days. Definitions and error categories were defined prior to data collection. Error types and numbers were collected and quantified on per-day or per-patient basis. RESULTS A total of 116 patient audit periods covering a total of 378 inpatient hospital days were examined. Inpatient insulin regimens on day 1 included correctional insulin only (51.7% of cases), neutral protamine Hagedorn ([NPH] 12%), and glargine (28.4%). A total of 199 administration errors occurred at a rate of 1.72 errors/patient-period and 0.53 errors/patient day. Missing documentation of doses (15.5% of all patients) and insulin being held without an order (25% of patients) were the most frequently occurring events. Other errors include transcription (7.5%), timing errors (22.7%), and lack of documentation of physician notification of hypoglycemia (12.6%). CONCLUSIONS Errors associated with insulin in the hospital are common and reveal a number of system errors that should be addressed. These data provide a foundation for future performance improvement.

Effects of an alternative cefepime dosing strategy in pulmonary and bloodstream infections caused by Enterobacter spp., Citrobacter freundii, and Pseudomonas aeruginosa: a single-center, open-label, prospective, observational study.

BACKGROUND Various dosing strategies for cefepime have been developed in an effort to maximize pharmacodynamic exposure of this agent against gram-negative infections. An assessment of cefepime dosing strategies is warranted given recent reports of poorer treatment outcomes associated with cefepime compared with other antibiotics, particularly in patients infected with gram-negative organisms with elevated MICs. OBJECTIVES The aims of this study were to compare the efficacy of cefepime IV at a dose of 1 g q8h (adjusted based on renal function) with those of other appropriate antimicrobials in the treatment of gramnegative pulmonary and bloodstream infections and to identify risk factors for treatment failure. METHODS This single-center, open-label, prospective, observational study was conducted at a tertiary care center (Barnes-Jewish Hospital, St. Louis, Missouri). Isolates from infections in adult patients with bacteremia or pulmonary infection caused by Pseudomonas aeruginosa, Enterobacter aerogenes, Enterobacter cloacae, or Citrobacter freundii were assessed in a noninterventional manner. Infections were identified using an electronic notification system. Patients receiving appropriate monotherapy against the studied isolate within 24 hours of culture attainment were stratified into 1 of 3 cohorts according to treatment outcome, as follows: treatment success (resolution of initial fever or elevated white blood cell count to normal values plus the presence of repeat negative cultures from the initial site or below the quantitative definition for infection), improvement (treatment success without repeat negative cultures), or treatment failure (persistent or repeat positive cultures for the original organism at the infected site despite appropriate and adequate antimicrobial therapy, lack of resolution in fever or leukocytosis, switch to an alternative antibiotic, or the addition of another antibiotic with gram-negative coverage after > or =3 days of the initial regimen, relapse of infection within 14 days, or mortality attributable to the index infection). Multivariate regression analysis was used to examine risk factors associated with treatment failure. RESULTS Data from 120 patients (56.7% male; mean age, 62.2 years) were analyzed. Treatment failure occurred in 48.6% (36/74) of patients who received cefepime versus 32.6% (15/46) of those who received other antibiotics; this difference was not statistically significant. The proportion of patients with markers of increased severity of illness (intensive care unit [P = 0.005] and mechanical ventilation [P = 0.002]) was significantly greater in the cefepime group compared with the group that received other antibiotics. Multivariate logistic regression identified infection with Pseudomonas aeruginosa (adjusted odds ratio [AOR], 1.40 [95% CI, 1.01-2.00]) and mechanical ventilation (AOR, 7.08 [95% CI, 1.80-31.3]) as being associated with treatment failure in patients who received cefepime. Mechanical ventilation (AOR, 3.97 [95% CI, 1.47-11.1]) and neutropenia (AOR, 5.26 [95% CI, 1.28-20.0]) were independent predictors of treatment failure among all patients studied. CONCLUSIONS Based on these results in this small cohort, the efficacy of this cefepime dosing strategy (1 g q8h) appeared to be similar to that of other antimicrobials.

Delayed-Onset Neutropenia with Divalproex Sodium

Objective: To report the development of neutropenia in a patient after almost 8 years of being stabilized on delayed-release divalproex sodium (DVPX). Case Summary: A 45-year-old man had been maintained on DVPX for nearly 8 years, with serum valproic acid concentrations of 85-120 mg/L and normal white blood cell (WBC) counts and absolute neutrophil counts (ANCs). Five months prior to the development of neutropenia (defined as ANC <1800 cells/μL), the patients DVPX dosage was decreased by 250 mg to 1250 mg every morning and 1500 mg every evening. After 2 months of that regimen, the DVPX dosage was increased back to 1500 mg twice daily. Three months alter that increase, the patients WBC count dropped to 3.7 × 103/μL and ANC was 1199 cells/μL Although the ANC was below 1800 cells/μL, he showed no physical manifestations consistent with neutropenia. DVPX was discontinued, and 2 weeks later the patients WBC count was 7.2 x 103/μL and ANC was 2290 cells/μL. Discussion: Although a complete blood cell count with differential is a commonly accepted form of therapeutic drug monitoring with DVPX, the monitoring is considered most necessary to identify dose-retated thrombocytopenia. However, neutropenia has been rarely associated with the use of DVPX and could contribute to the development of different types of infection, including those of a bacterial, viral, or fungal origin. Although neutropenia is generally mild in severity, potentially severe DVPX-associated neutropenia can occur any time during the course of therapy, although it is most common within the first few months of treatment. In this case, DVPX was the probable cause of the neutropenia, according to the Naranjo probability scale. However, this case of neutropenia is atypical with respect to the timeframe in which it developed and was identified. Although the documented laboratory findings suggest neutropenia, the patient did not experience any clinical complications as a result. The late onset of the patients neutropenia is unlike other cases that have been documented in the literature. Conclusions: Hematologic therapeutic drug monitoring continues to be clinically important regardless of whether the patient is early in therapy or even years later in the course. In this patient, continued regular therapeutic drug monitoring identified a suspected drug-related complication and the medication was able to be discontinued without the development of clinical complications.

Weight‐based insulin dosing for acute hyperkalemia results in less hypoglycemia

Hyperkalemia treatment with intravenous insulin has been associated with hypoglycemia. This single-center, retrospective study compared the effects on hypoglycemia between weight-based insulin dosing (0.1 U/kg of body weight up to a maximum of 10 U) compared to standard flat doses of 10 U among patients weighing less than 95 kg. Of the 132 charts randomly selected for review, hypoglycemic events (blood glucose <70 mg/dL) were reduced from 27.3% in the 10-U group to 12.1% in the weight-based group (P = 0.05). The number of affected patients was reduced with 19.7% in the 10-U group and 10.6% in the weight-based group (P = 0.22). The potassium-lowering effects of these 2 strategies were similar between groups. Female patients and those with baseline glucose values <140 mg/dL were at increased risk for hypoglycemia. Weight-based insulin dosing (0.1 U/kg) for acute hyperkalemia therapy resulted in less hypoglycemia without impacting potassium lowering. Journal of Hospital Medicine 2016;11:355-357.