Philip Grgurich

Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection

BACKGROUND The incidence and severity of Clostridium difficile infections are increasing. Acid-suppressive therapy has been suggested as a risk factor for C difficile, but this remains controversial. METHODS We conducted a pharmacoepidemiologic cohort study, performing a secondary analysis of data collected prospectively on 101 796 discharges from a tertiary care medical center during a 5-year period. The primary exposure of interest was acid suppression therapy, classified by the most intense acid suppression therapy received (no acid suppression, histamine(2)-receptor antagonist [H(2)RA] therapy, daily proton pump inhibitor [PPI], and PPI more frequently than daily). RESULTS As the level of acid suppression increased, the risk of nosocomial C difficile infection increased, from 0.3% (95% confidence interval [CI], 0.21%-0.31%) in patients not receiving acid suppressive therapy to 0.6% (95% CI, 0.49%-0.79%) in those receiving H(2)RA therapy, to 0.9% (95% CI, 0.80%-0.98%) in those receiving daily PPI treatment, and to 1.4% (1.15%-1.71%) in those receiving more frequent PPI therapy. After adjustment for comorbid conditions, age, antibiotics, and propensity score-based likelihood of receipt of acid-suppression therapy, the association persisted, increasing from an odds ratio of 1 (no acid suppression [reference]) to 1.53 (95% CI, 1.12-2.10) (H(2)RA), to 1.74 (95% CI, 1.39-2.18) (daily PPI), and to 2.36 (95% CI, 1.79-3.11) (more frequent PPI). Similar estimates were found with a matched cohort analysis and with nested case-control techniques. CONCLUSIONS Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study

IntroductionWhile propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol.MethodsCritically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS.ResultsAmong 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar.ConclusionsDespite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.

Diagnosis of ventilator-associated pneumonia: controversies and working toward a gold standard.

Purpose of review The aim is to discuss the clinical, microbiologic, and radiological criteria used in the diagnosis of ventilator-associated pneumonia (VAP), distinguish between ventilator-associated tracheobronchitis (VAT) and VAP, and reconcile the proposed Centers for Disease Control surveillance criteria with clinical practice. Recent findings Numerous ventilator-associated complications (VACs), including VAP and VAT, may occur in critically ill, intubated patients. A variety of definitions for identifying VAP have been proposed, but there is no diagnostic gold standard. The proposed surveillance definition will identify infectious and noninfectious VAC, including VAP and VAT, but this definition may be inadequate for clinical practice. Summary The clinical characteristics of VAP and VAT are similar and include fever, leukocytosis, and purulent sputum. An infiltrate on chest radiograph is consistent with VAP but lacks diagnostic precision, so it is not a criterion in the proposed surveillance definition and should be interpreted cautiously by clinicians. Microbiologically, quantitative and semiquantitative endotracheal aspirate cultures may be employed to diagnose VAP and VAT. Positive bronchoalveolar lavage and protected specimen brush cultures are useful only for the diagnosis of VAP. Experts should collaborate to develop consensus definitions for VAP and VAT that can be applied in practice.

Management and prevention of ventilator-associated pneumonia caused by multidrug-resistant pathogens

Ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens is a leading healthcare-associated infection in mechanically ventilated patients. The incidence of VAP due to MDR pathogens has increased significantly in the last decade. Risk factors for VAP due to MDR organisms include advanced age, immunosuppression, broad-spectrum antibiotic exposure, increased severity of illness, previous hospitalization or residence in a chronic care facility and prolonged duration of invasive mechanical ventilation. Methicillin-resistant Staphlococcus aureus and several different species of Gram-negative bacteria can cause MDR VAP. Especially difficult Gram-negative bacteria include Pseudomonas aeruginosa, Acinetobacter baumannii, carbapenemase-producing Enterobacteraciae and extended-spectrum β-lactamase producing bacteria. Proper management includes selecting appropriate antibiotics, optimizing dosing and using timely de-escalation based on antibimicrobial sensitivity data. Evidence-based strategies to prevent VAP that incorporate multidisciplinary staff education and collaboration are essential to reduce the burden of this disease and associated healthcare costs.

Impact of Students Pharmacists on the Medication Reconciliation Process in High-Risk Hospitalized General Medicine Patients

Objective. To compare the accuracy of medication lists obtained by student pharmacists, nurses, and physicians, and quantify the number of discrepancies identified as part of the medication reconciliation process. Methods. Between May and July 2012, patients admitted to an internal medicine team at a 350-bed tertiary academic medical center were assessed for inclusion in the study. Physicians and/or nurses conducted medication reviews for these patients at the time of admission, while student pharmacists conducted medication reconciliation. Results. Eighty-six patients were assessed, and 52 met all inclusion criteria. A total of 268 discrepancies were identified as part of the medication reconciliation performed by the student pharmacists, approximating 5 discrepancies per patient (range 0-13). Student pharmacists identified 532 preadmission medications, significantly more than did nurses (355) or physicians (368), p=0.006. Conclusion. Student pharmacists, with appropriate oversight, can be used in several tasks that previously may have been designated to pharmacists only, such as medication reconciliation.

Strategies for Prevention of Ventilator-Associated Pneumonia: Bundles, Devices, and Medications for Improved Patient Outcomes

Abstract Ventilator-associated pneumonia is associated with significant patient morbidity, mortality, and increased health care costs. In the current economic climate, it is crucial to implement cost-effective prevention strategies that have proven efficacy. Multiple prevention measures have been proposed by various expert panels. Global strategies have focused on infection control, and reduction of lower airway colonization with bacterial pathogens, intubation, duration of mechanical ventilation, and length of stay in the intensive care unit. Routine use of the Institute for Healthcare Improvement ventilator care bundle is widespread, and has been clearly demonstrated to be an effective method for reducing the incidence of ventilator-associated pneumonia. In this article, we examine specific aspects of the Institute for Healthcare Improvement bundle, better-designed endotracheal tubes, use of antibiotics and probiotics, and treatment of ventilator-associated tracheobronchitis to prevent ventilator-associated pneumonia.

A Symptom-Triggered Benzodiazepine Protocol Utilizing SAS and CIWA-Ar Scoring for the Treatment of Alcohol Withdrawal Syndrome in the Critically Ill:

Background: There are limited data on the efficacy of symptom-triggered therapy for alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU). Objective: To evaluate the safety and efficacy of a symptom-triggered benzodiazepine protocol utilizing Riker Sedation Agitation Scale (SAS) scoring for the treatment of AWS in the ICU. Methods: We performed a before-and-after study in a medical ICU. A protocol incorporating SAS scoring and symptom-triggered benzodiazepine dosing was implemented in place of a protocol that utilized the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale and fixed benzodiazepine dosing. Results: We enrolled 167 patients (135 in the preintervention and 32 in the postintervention group). The median duration of AWS was shorter in the postintervention (5, interquartile range [IQR] = 4-8 days) than in the preintervention group (8, IQR = 5-12 days; P < 0.01). Need for mechanical ventilation (31% vs 57%, P = 0.01), median ICU length of stay (LOS; 4, IQR = 2-7, vs 7, IQR = 4-11 days, P = 0.02), and hospital LOS (9, IQR = 6-13, vs 13, IQR = 9-18 days; P = 0.01) were less in the postintervention group. There was a reduction in mean total benzodiazepine exposure (74 ± 159 vs 450 ± 701 mg lorazepam; P < 0.01) in the postintervention group. Conclusion: A symptom-triggered benzodiazepine protocol utilizing SAS in critically ill patients is associated with a reduction in the duration of AWS treatment, benzodiazepine exposure, need for mechanical ventilation, and ICU and hospital LOS compared with a CIWA-Ar–based protocol using fixed benzodiazepine dosing.

Feasibility of a Collaborative, Prospective Interdisciplinary Review and Pharmacy-Based Dispensing Process for Prothrombin Complex Concentrate:

Background: Therapeutic options for rapid reversal of vitamin K antagonist therapy include 4-factor prothrombin complex concentrate (PCC4) and fresh frozen plasma (FFP). These agents have unique requirements for preparation, potential adverse effects, and cost-effectiveness considerations. Objective: To retrospectively assess whether our process for collaborative prospective review and pharmacy preparation facilitates timely and safe warfarin reversal with PCC4 as compared with FFP and to compare effectiveness and safety of the agents in practice. Methods: We performed a retrospective, single-center, before and after cohort study of patients requiring warfarin reversal for life-threatening bleeding or urgent invasive procedures over an 18-month period. The primary end point was time from ordering of reversal agent to administration. Secondary end points measured time to therapeutic effect and rates of adverse events. Results: Of 98 patients studied, 72 received FFP, and 26 received PCC4. The median times from ordering to administration of FFP and PCC4 were 69 and 44 minutes, respectively (P = 0.015). Median time from ordering to end of infusion was significantly shorter for PCC4 compared with FFP (54 vs 151 minutes, respectively; P < 0.0001). In all, 72% of PCC4 patients and 28% of FFP patients achieved the goal international normalized ratio (INR) of ≤1.4 at the first INR check (P < 0.0001). Adverse reactions occurred in 4% of patients in each group. Conclusion: In routine clinical practice incorporating collaborative prospective review and dispensing from the institution’s pharmacy, PCC4 was associated with faster administration, a higher rate of INR correction, and similar rates of adverse events compared with FFP.

410: EXPERIENCES AND PERCEPTIONS OF PROGRAM DIRECTORS AND PRECEPTORS ON THE SCCM CPP SECTION JOURNAL CLUB

Learning Objectives: The SCCM Clinical Pharmacy and Pharmacology (CPP) Section Education Committee has facilitated a monthly journal club webinar since 2007 in which PGY-2 critical care pharmacy residents thoroughly evaluate and present publications relevant to critical care pharmacotherapy. The purpose of this research was to describe resident program directors’ (RPD) and preceptors’ experience and perceptions of the journal club webinar. Methods: An 18-item survey was developed, evaluated for face and content validity by six critical care pharmacists, and administered through an online survey tool to RPDs and preceptors of programs whose residents presented a journal club at any time from 2011-2016. Domains surveyed were demographics, precepting experience, and journal club feedback. Results were summarized using descriptive statistics. Results: Of the 57 RPDs and preceptors from unique programs that had at least one participant in the journal club, 29 (50.9%) responded. Most respondents (n=27; 93.1%) have viewed the journal club for more than two years. RPDs and preceptors felt that participation in the journal club increased their knowledge in the article content (n=13/19; 68.4%) and improved capability to provide verbal feedback (n=10/19; 52.6%). On a 5-point Likert scale (1=strongly disagree, 5=strongly agree), most RPDs and preceptors (n=27) felt participation in the journal club increased their involvement in the CPP Section (median 4, IQR 3-4), and their resident’s future involvement with the journal club (median 5, IQR 4-5), CPP Section (median 4, IQR 3-5), and SCCM (median 4, IQR 4-5). Most RPDs and preceptors (n=24) felt that it was extremely likely they would have future residents participate in the journal club (median 5, IQR 5-5). Conclusions: RPDs and preceptors felt the SCCM CPP Section journal club was beneficial in increasing content knowledge and the ability to provide feedback. Participation increased their resident’s future involvement within SCCM, the CPP Section, and the journal club. Most RPDs and preceptors would have future PGY-2 critical care residents participate in the journal club.