Oral bioavailability of clonidine in children.

BACKGROUND: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children. METHODS: Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg(-1) mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability. RESULTS: There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l·h(-1) per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l·h(-1) per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l·70 kg(-1), peripheral volume of distribution (V2) 113 (33.9; 91-131) l·70 kg(-1). The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654). CONCLUSIONS: Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (T(max) 1.04 h, C(max) 0.77 mcg·l(-1)). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults.

The direct and indirect costs of opioid-induced constipation.

CONTEXT: Treatment with strong opioids is connected with frequent and problematic side effects. One of the most common side effects is opioid-induced constipation (OIC). The discomfort of OIC can limit the effectiveness of pain therapy. Because constipation typically persists for as long as opioid therapy is administered, its effects on the quality of life (QoL) of patients need to be taken seriously. Data and published studies on the cost implications of OIC are, however, scarce. OBJECTIVES: To estimate the direct and indirect costs of OIC in a defined patient population during treatment with strong opioids. METHODS: The study is based on patient data from a Swedish noninterventional study, UPPSIKT. The cost analysis is based on 197 patients treated with strong opioids over a six-month period. Direct and indirect costs in this article are calculated per patient-month, and the cost for OIC is estimated as the difference in mean costs between months with and without constipation. RESULTS: The total costs per patient-month for patients with severe constipation are significantly higher than those for patients with mild, moderate, or no constipation. Patients with severe constipation have the highest total costs, Euro (EUR) 1525 per patient-month, whereas patients with mild, moderate, and no problems cost EUR 1196, EUR 1088, and EUR 1034, respectively. CONCLUSION: Opioid use is costly to society, and the costs vary with OIC severity. OIC is discomforting, affects the QoL of patients, and can limit an effective pain therapy.

Clonidine: an alternative to benzodiazepines for premedication in children.

PURPOSE OF REVIEW: The aim of this review is to summarize the use of clonidine for paediatric premedication and to make a comparison with benzodiazepines. A routine clonidine premedication protocol is also presented. RECENT FINDINGS: In the US 50% of young children undergoing surgery receive premedication and midazolam is the most frequently used drug. The number of trials that compare midazolam with active controls are few and this premedicant is not adequately validated. Clonidine is still used as premedication in a small number of centres but the literature on paediatric use of clonidine is steadily growing. A recent review article has concluded that the use of clonidine does enhance the quality of perioperative management in infants and children and more recent publications support the use of clonidine for premedication. Its effect on the circulation is mild but routine atropine administration is recommended. Contraindications to the use of clonidine are few. Apart from a general overview on the effects of clonidine this article will also summarise the published trials that have compared clonidine with benzodiazepines for premedication in children. SUMMARY: Midazolam the most commonly used drug for paediatric premedication worldwide. Despite having a number of beneficial effects it is far from an ideal premedicant, especially concerning its effect on cognition/amnesia, confusion and long-term behavioural disturbances. Clonidine lacks the majority of the negative effects associated with midazolam and is associated with a number of beneficial perioperative effects. Our clinical experience of replacing midazolam with clonidine as premedicant in children, including also outpatients, has been favourable.

Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is still common, especially among female patients. Our hypothesis is that coinduction with clonidine reduces the incidence of PONV in adult patients undergoing breast cancer surgery. METHODS: Sixty-eight women premedicated with midazolam were randomly allocated to coinduction with intravenous clonidine (group C) or placebo (group P) in this prospective, double-blind study. Anesthesia was standardized (laryngeal mask airway, fentanyl, propofol, sevoflurane, nitrous oxide, and oxygen). Hemodynamic parameters and the requirements for propofol, sevoflurane, and the postoperative need for ketobemidone were noted. The primary endpoints studied were the number of PONV-free patients and patient satisfaction with respect to PONV. RESULTS: Patients in group C had a significantly reduced need for propofol (P < 0.04) and sevoflurane (P < 0.01) and a reduced early need for ketobemidone (P < 0.04). There were significantly more PONV-free patients in group C compared with group P (20 and 11 of 30, respectively; P < 0.04). The number needed to treat was 3.3 (95% confidence interval, 1.8, 16.9). Intraoperative blood pressure, postoperative heart rate, and postoperative blood pressure were all significantly lower in group C compared with group P, but were not considered to be of clinical importance. No negative side effects were recorded. CONCLUSION: Coinduction with clonidine significantly increased the number of PONV-free patients after breast cancer surgery with general anesthesia.