Cefazolin Monotherapy Versus Cefazolin Plus Aminoglycosides for Antimicrobial Prophylaxis of Type III Open Fractures.

BACKGROUND: There are conflicting recommendations between organizations regarding aminoglycoside use for the prophylaxis of type III open fractures. STUDY QUESTION: To compare cefazolin monotherapy versus cefazolin plus aminoglycoside therapy for prophylaxis of type III open fractures in trauma patients. STUDY DESIGN: This was a multicenter, retrospective, cohort study conducted in 3 academic medical centers in the United States. Consecutive adult trauma patients with type III open fractures between January 2014 and September 2016 were included. Patients were divided into 2 groups: (1) cefazolin monotherapy versus (2) cefazolin plus aminoglycoside. MEASURES AND OUTCOMES: The primary outcome measure was the occurrence of infection at the open fracture site. The secondary outcome measure was the occurrence of acute kidney injury. RESULTS: There were 134 patients included in the study cohort. Of these, 39 received cefazolin monotherapy and 95 received cefazolin plus aminoglycoside. Overall, the mean age was 39 ± 15 years, 105 (78%) were male, and the most common fracture location was tibia/fibula (n = 74, 56%). Infection at the open fracture site occurred in 6 of 39 patients (15%) in the cefazolin monotherapy group and 15 of 95 patients (16%) in the cefazolin plus aminoglycoside group (P = 1.000). Acute kidney injury occurred in 0 of 39 (0%) in the cefazolin monotherapy group and 1 of 95 (1%) in the cefazolin plus aminoglycoside group (P = 1.000). CONCLUSIONS: Cefazolin monotherapy may be appropriate for antimicrobial prophylaxis of type III open fractures in trauma patients.

Trigger alerts associated with laboratory abnormalities on identifying potentially preventable adverse drug events in the intensive care unit and general ward.

BACKGROUND: Medication safety strategies involving trigger alerts have demonstrated potential in identifying drug-related hazardous conditions (DRHCs) and preventing adverse drug events in hospitalized patients. However, trigger alert effectiveness between intensive care unit (ICU) and general ward patients remains unknown. The objective was to investigate trigger alert performance in accurately identifying DRHCs associated with laboratory abnormalities in ICU and non-ICU settings. METHODS: This retrospective, observational study was conducted at a university hospital over a 1-year period involving 20 unique trigger alerts aimed at identifying possible drug-induced laboratory abnormalities. The primary outcome was to determine the positive predictive value (PPV) in distinguishing drug-induced abnormal laboratory values using trigger alerts in critically ill and general ward patients. Aberrant lab values attributed to medications without resulting in an actual adverse event ensuing were categorized as a DRHC. RESULTS: A total of 634 patients involving 870 trigger alerts were included. The distribution of trigger alerts generated occurred more commonly in general ward patients (59.8%) than those in the ICU (40.2%). The overall PPV in detecting a DRHC in all hospitalized patients was 0.29, while the PPV in non-ICU patients (0.31) was significantly higher than the critically ill (0.25) (p = 0.03). However, the rate of DRHCs was significantly higher in the ICU than the general ward (7.49 versus 0.87 events per 1000 patient days, respectively, p < 0.0001). Although most DRHCs were considered mild or moderate in severity, more serious and life-threatening DRHCs occurred in the ICU compared with the general ward (39.8% versus 12.4%, respectively, p < 0.001). CONCLUSIONS: Overall, most trigger alerts performed poorly in detecting DRHCs irrespective of patient care setting. Continuous process improvement practices should be applied to trigger alert performance to improve clinician time efficiency and minimize alert fatigue.

Use of Prophylactic Ondansetron with Intravenous Opioids in Emergency Department Patients: A Prospective Observational Pilot Study.

BACKGROUND: The current literature suggests that the prophylactic use of antiemetics is ineffective at preventing nausea or vomiting caused by opioids in the emergency department (ED). While there is no data evaluating ondansetron's efficacy for preventing opioid-induced nausea and vomiting, this practice remains common despite a lack of supporting evidence. OBJECTIVES: This study aimed to identify if prophylactic ondansetron administered with intravenous (IV) opioids prevents opioid-induced nausea or vomiting. METHODS: This prospective observational study was conducted in the ED at two academic medical institutions. Patients were eligible for enrollment if they were prescribed an IV opioid with or without IV ondansetron and absence of baseline nausea. Patients' level of nausea was evaluated at baseline, 5 min, and 30 min after an IV opioid was administered and then observed for 2 hours. RESULTS: One hundred thirty-three patients were enrolled, with 90% of patients presenting with a chief complaint of pain. Sixty-four (48.1%) patients received an IV opioid alone and 69 (51.9%) patients received both IV ondansetron and an IV opioid. Twenty-three (17.3%) patients developed nausea caused by opioid administration. One (0.75%) patient had an emetic event and 3 (2.3%) patients required rescue antiemetics during their observation period. Rate of nausea was similar between treatment groups 5 min after the opioid was administered (p = 0.153). There was no statistical difference in emesis, rescue medication requirements, or nausea severity between treatment groups. CONCLUSION: Our trial found that ondansetron did not appear to be effective at preventing opioid-induced nausea or vomiting. These findings and previous literature suggest prophylactic ondansetron should not be given to ED patients who are receiving IV opioids.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

OBJECTIVE: Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. DESIGN: Multicenter, observational study SETTING: : Medical ICUs at three academic medical centers. PATIENTS: Adult patients (age ≥ 18 yr old) receiving medication therapy. INTERVENTIONS: All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). CONCLUSION: Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

Conivaptan for treatment of hyponatremia in neurologic and neurosurgical adults.

OBJECTIVE: To review the literature evaluating the clinical safety and efficacy of conivaptan in the management of hyponatremia in a neurologic and neuro-surgical adult patient population. DATA SOURCES: A literature search was conducted using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials (1966-May 2013). Search limits were English, human, and adult using the terms vasopressin receptor antagonist, conivaptan, tolvaptan, lixivaptan, neurology, neurological disorder, neurosurgery, neurointensive care, and neurocritical care. STUDY SELECTION AND DATA EXTRACTION: All case reports, case series, and clinical trials investigating the use of conivaptan in neurosurgical patients were included. DATA SYNTHESIS: Seven reports were identified using conivaptan as monotherapy or adjunctive treatment for hyponatremia in a neurosurgical patient population. One study was a prospective, randomized, controlled trial, while 6 reports were case reports or case series. The prospective randomized trial found a significant increase in serum sodium concentration over baseline with a conivaptan 20-mg intravenous bolus dose followed by a 20-mg/day continuous infusion for 24 hours compared to "usual care" at 6 hours (7.0 ± 1.7 vs -0.6 ± 2.1 mEq/L, respectively; p = 0.008) and 36 hours (8.0 ± 5.6 vs -1.7 ± 2.1 mEq/L, respectively; p = 0.05) after treatment. One case series found that the mean serum sodium remained significantly increased from baseline up to 72 hours (5.12 ± 4.0 mEq/L; p < 0.001) after a single conivaptan 20-mg intravenous bolus dose. All reports demonstrated clinical effectiveness of conivaptan in significantly increasing serum sodium concentrations following administration compared to baseline. However, the clinical significance of this finding remains debatable since some of these patients remained hyponatremic. CONCLUSIONS: Overall, conivaptan is a promising and well-tolerated agent for the management of hyponatremia in neurologic and neurosurgical patients. However, its use should be limited to patients in whom conventional therapies fail or as adjunctive therapy.