Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance.

OBJECTIVE: Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients. DESIGN: Observational comparative study. SETTING: Tertiary critical care unit. PATIENTS: Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients. INTERVENTIONS: Patients received intravenous erythromycin 200 mg twice daily for feed intolerance. MEASUREMENTS: Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤ 250 mL with a feeding rate ≥ 40 mL/h, was recorded over 7 days. RESULTS: At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = -.47, p = .049) and 7-hr (r = -.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥ 0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin. CONCLUSIONS: In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.

Quality of requests for serum digoxin concentrations: experience from an Australian regional health service.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Therapeutic drug monitoring of serum digoxin concentrations (SDC) is considered useful in enhancing the therapeutic benefits of digoxin and minimizing the incidence of adverse drug reactions. * The quality of requests for SDC has been reported to be generally unsatisfactory. However, studies have focused on few information parameters. * A better knowledge of these issues might be useful to target appropriate areas of weakness within heathcare systems. WHAT THIS STUDY ADDS: * The poor quality of the information in SDC requests involves a wide range of codes from the contact details of the requester to the time interval between the last dose of digoxin and blood sampling. * Misuse of the therapeutic drug monitoring service is common across different specialties and healthcare settings. AIMS: To assess the quality of the information provided with serum digoxin concentration (SDC) requests received by a therapeutic drug monitoring service in a regional health service. METHODS: We conducted a retrospective audit of a consecutive series of 685 SDC requests during a 7-month period. Information regarding (i) contact details, (ii) reasons for request, (iii) dose, (iv) route of administration, (v) concurrent therapy, (vi) treatment duration and (vii) time interval between the last dose and sampling was reviewed and coded as appropriate or inappropriate/missing. Data were analysed according to the origin of request, i.e. from different specialties/wards (emergency department and critical care, cardiology and coronary care unit, medicine and aged care, surgery, and general/private practice) and healthcare settings (teaching hospital, geriatric hospital and general/private practice). RESULTS: The quality of SDC requests was generally poor across different specialties and healthcare settings. The information provided for the coded parameters was appropriate only in 19.1% (i), 6.4% (ii), 54.7% (iii), 45.8% (iv), 12.8% (v), 32.9% (vi) and 47.1% (vii) of cases. No SDC request was complete in all the information codes. SDC requests from general/private practice lacked more often details regarding the dose (information provided in 46.7% of requests, P = 0.007 vs. other specialties; P = 0.02 vs. other settings) and the route of administration (20.0%, P < 0.001 vs. other specialties and vs. other settings). SDC requests from the emergency department and critical care unit lacked more often details regarding the treatment duration (22.6%, P < 0.001 vs. other specialties) and the time interval between the last dose and blood sampling (40.1%, P = 0.01 vs. other specialties). CONCLUSIONS: The quality of the information in SDC requests is poor across different specialties and healthcare settings. Educational strategies to ensure the appropriate use of this service are urgently needed.