Objective Ketamine is an N‐methyl‐D‐aspartate antagonist with emerging evidence assessing its use as a continuous infusion agent to provide concomitant analgesia and sedation. The role of ketamine as adjunctive therapy in mechanically ventilated patients is unclear. This study sought to investigate the impact of adjunctive continuous infusion ketamine on concomitant analgesic and sedative dosing while providing goal comfort in mechanically ventilated patients. Methods This retrospective two‐center intrapatient comparison study included mechanically ventilated adult ICU patients who received continuous infusion ketamine with at least one other analgesic or sedative infusion. The primary outcome assessed percent relative change in concomitant analgesic‐sedative doses 24 hours after ketamine initiation. Secondary outcomes included percent of Richmond Agitation and Sedation Score (RASS) assessments at goal, adverse effects, and delirium incidence. Exploratory evaluation of independent factors associated with ketamine responders (50% or more relative reduction in analgesic‐sedative dosing requirements at 24 hrs) and nonresponders (less than 50% relative reduction) was performed using multivariate logistic regression. Results Overall, 104 patients were included. A total of 160 concomitant analgesic‐sedative infusions were used in combination with ketamine, most commonly fentanyl (98 [61.3%]) and propofol (46 [28.8%]). A 20% (interquartile range [IQR] −63.6 to 0.0, p<0.001) relative reduction in total analgesic‐sedative infusion pharmacotherapy was achieved at 24 hours after ketamine initiation. Analgesic and sedative infusion doses decreased at 24 hours (fentanyl: pre, 175 μg/hr [IQR 100–200 μg/hr] vs post, 125 μg/hr [IQR 50–200 μg/hr], p<0.001; propofol: pre, 42.5 μg/kg/min [IQR 20.0–60.0 μg/kg/min] vs post, 20.0 μg/kg/min [IQR 3.8–31.3 μg/kg/min], p<0.001). Median percent time within goal RASS improved after ketamine initiation (pre, 7.1% [0–40%] vs post, 25% [0–66.7%], p=0.005). No differences were observed in secondary outcomes between responders and nonresponders, except a longer non‐ICU hospital length of stay in responders. Independent factors associated with ketamine response included a lower body mass index, higher starting dose of ketamine, lower severity of illness, and need for multiple concomitant analgesic‐sedative infusions before initiation of ketamine. Conclusions Adjunctive continuous infusion ketamine promotes analgesic and sedative dose‐sparing effects in mechanically ventilated patients while improving time spent within goal sedation range. Further prospective research is warranted.

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BACKGROUND Numerous medical conditions require timely medication administration in the emergency department (ED). Automated dispensing systems (ADSs) store premixed common doses at the point-of-care to minimize time to administration, but the use of such automation to improved time to medication administration has not been studied. Since vancomycin is a commonly used empiric antimicrobial, we sought to quantify the effect of using an ADS on time to drug delivery in patients presenting to the ED. The study aimed to determine the efficacy of utilizing an ADS to improve time to administration of vancomycin and determine any negative effects on dosing appropriateness. METHODS The institional review board approved the retrospective quality improvement study took place in a single, urban academic tertiary care ED with an annual census of 80 000. Study subjects were all patients receiving vancomycin for the management of sepsis between March 1 to September 30, 2008 and the same time period in 2009. The primary outcome was the proportion of patients who received vancomycin within one hour of bed placement and the secondary outcome was dosing appropriateness. RESULTS Sixty-three patients had weight and dosing information available (29 before and 34 after intervention) and were included in the study. Before intervention, no patient received vancomycin in less than 60 minutes, while after intervention 14.7% of the patients received it in less than 60 minutes (difference in proportions 14.7%, 95% CI 0.39%-30.0%, P=0.04). A similar proportion of the patients received correct dosing before and after intervention (44.8% vs. 41.2%, difference in proportions 3.7%, 95% CI -20.0%-26.7%, P=0.770). CONCLUSION The use of an ADS may improve the timing of medication administration in patients presenting to the ED without affecting dosing appropriateness.

Study Objective To evaluate extended‐infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD). Design Prospective, open‐label, PK study. Setting Intensive care units at a large, academic, tertiary‐care medical center. Patients Ten critically ill adults who were receiving cefepime 2 g intravenously every 8 hours as a 4‐hour infusion while receiving CVVH (eight patients) or CVVHD (two patients). Intervention Two sets of five serum cefepime concentrations were collected for each patient to assess pharmacokinetics before and during presumed steady state. Concurrent serum and CRRT effluent samples were collected at hours 1, 2, 3, 4, and 8 after the first cefepime dose and after either the fourth, fifth, or sixth (steady‐state) cefepime doses. Measurements and Main Results Reversed‐phase high‐performance liquid chromatography was used to determine free cefepime concentrations. PK analyses included CRRT clearance, half‐life, and sieving coefficient or saturation coefficient. Cefepime peak (4 hrs) concentrations, trough (8 hrs) concentrations (Cmin), and minimum inhibitory concentration breakpoint of 8 µg/ml for the pathogen (MIC8) were used to evaluate attainment of pharmacodynamic targets: 100% of the dosing interval that free drug remains above MIC8 (100% fT > MIC8), 100% fT > 4 × MIC8 (optimal), percentage of time fT > 4 × MIC8 (%fT > 4 × MIC8) at steady state, and ratio of Cmin to MIC8 (fCmin/MIC8). Total CRRT effluent flow rate was a mean ± SD of 30.1 ± 5.4 ml/kg/hr, CRRT clearance was 39.6 ± 9.9 ml/min, and half‐life was 5.3 ± 1.7 hours. Sieving coefficient or saturation coefficient were 0.83 ± 0.13 and 0.69 ± 0.22, respectively. First and steady‐state dose Cmin were 23.4 ± 10.1 µg/ml and 45.2 ± 14.6 µg/ml, respectively. All patients achieved 100% fT > MIC8 on first and steady‐state doses. First and steady‐state dose 100% fT > 4 × MIC8 were achieved in 22% (2/9 patients) and 87.5% (7/8 patients) of patients, respectively. The mean %fT > 4 × MIC8 at steady state was 97.5%. The fCmin/MIC8 was 2.92 ± 1.26 for the first dose and 5.65 ± 1.83 at steady state. Conclusion Extended‐infusion cefepime dosing in critically ill patients receiving CRRT successfully attained 100% fT > MIC8 in all patients and an appropriate fCmin/MIC8 for both first and steady‐state doses. All but one patient achieved 100% fT > 4 × MIC8 at steady state. No significant differences were observed in PK properties between first and steady‐state doses among or between patients. It may be reasonable to initiate an empiric or definitive regimen of EI cefepime in critically ill patients receiving concurrent CRRT who are at risk for resistant organisms. Further research is needed to identify the optimal dosing regimen of EI cefepime in this patient population.

A stepwise approach to the development and implementation of ambulatory care clinical pharmacy services has facilitated the expansion of pharmacist-managed anticoagulation clinics across an integrated health system. This may serve as a valuable template for other systems as they strive to develop medication therapy management services.

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