A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices.

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half-time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.

Compliance with perioperative prophylaxis guidelines and the use of novel outcome measures.

Postoperative wound infections represent an important source of morbidity and mortality in children. Perioperative antibiotic prophylaxis has been shown to decrease the risk of developing infections and hospital guidelines surrounding antibiotic use exist to standardize patient care. Despite supporting evidence, rates of compliance with guidelines vary. Quality improvement initiatives have been introduced to improve compliance with intraoperative antibiotic guidelines. Thorough infection surveillance, including antibiotic provision in presurgical checklists, computerized voice antibiotic administration prompts, and national feedback systems are now increasingly common. Few studies have been conducted investigating the effectiveness of prophylactic antibiotics in children. Outcome measures such as morbidity and mortality and return to the operating room can be used to examine the relationship between antibiotic use and patient outcome but these measures are limited in that they occur infrequently or are subjective and difficult to measure. Metrics such as days alive out of hospital and length of hospital stay may be useful alternatives for ongoing monitoring of infections and identifying improvements in patient outcomes. Guidelines on antibiotic prophylaxis have facilitated an increase in the correct provision of perioperative antibiotics and a reduction in the incidence of postoperative infection. Measures of patient outcome such as days alive out of hospital and length of hospital stay are easy to collect and calculate but further work is needed to confirm the utility of these measures for monitoring infection rates.

The impact of clonidine on sedation after adenotonsillectomy: a prospective audit.

AIMS: Clonidine may be used intraoperatively to decrease emergence delirium in children, but the drug's impact on postoperative sedation is poorly quantified. METHODS: A prospective audit of children (≤15 years) undergoing (adeno) tonsillectomy or adenoidectomy over a period of 4 months was carried out. All children received sevoflurane for induction and maintenance of anesthesia. The use of clonidine as an adjunct was left to the discretion of the anesthesiologist. Postoperative sedation was assessed using the University of Michigan Sedation Scale (UMSS) at 30 min intervals until discharge. Arousal was characterized using a zero asymptote model. The impact of clonidine dose on half-time to an awake state after anesthesia was investigated using nonlinear mixed effects models. Survival analysis was used to explore the effect of clonidine dose on discharge time. RESULTS: The mean age of children (n = 177) was 5.4 sd 3.3 years, range 0.8-15.0 years and weight was 23.8 SD 11.4 kg, range 10.0-76.4 kg. There were 73 children given clonidine 0.29-4.80 mcg·kg(-1) after induction. The half-time to emergence was 10.8 (95% CI 8.5, 13.2) min. Emergence half-time was increased to 15 min with clonidine 0.5 mcg·kg(-1), 20 min with clonidine 1.5 mcg·kg(-1), 25 min with clonidine 2 mcg·kg(-1) and 65 min with clonidine 4 mcg·kg(-1). Clonidine doses 0.5-3 mcg·kg(-1) did not affect hospital discharge time. CONCLUSIONS: Clonidine administered intraoperatively for (adeno) tonsillectomy or adenoidectomy prolonged emergence from anesthesia. Doses of 0.5-3 mcg·kg(-1) caused greater sedation in the postanesthesia care unit but did not impact on hospital discharge times.