Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients

<p>Abstract</p> <p>Background</p> <p>Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.</p> <p>Methods</p> <p>Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.</p> <p>Results</p> <p>Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.</p> <p>Conclusion</p> <p>Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.</p

Postoperative Adverse Outcomes in Intellectually Disabled Surgical Patients: A Nationwide Population-Based Study

Intellectually disabled patients have various comorbidities, but their risks of adverse surgical outcomes have not been examined. This study assesses pre-existing comorbidities, adjusted risks of postoperative major morbidities and mortality in intellectually disabled surgical patients.A nationwide population-based study was conducted in patients who underwent inpatient major surgery in Taiwan between 2004 and 2007. Four controls for each patient were randomly selected from the National Health Insurance Research Database. Preoperative major comorbidities, postoperative major complications and 30-day in-hospital mortality were compared between patients with and without intellectual disability. Use of medical services also was analyzed. Adjusted odds ratios using multivariate logistic regression analyses with 95% confidence intervals were applied to verify intellectual disability's impact.Controls were compared with 3983 surgical patients with intellectual disability. Risks for postoperative major complications were increased in patients with intellectual disability, including acute renal failure (odds ratio 3.81, 95% confidence interval 2.28 to 6.37), pneumonia (odds ratio 2.01, 1.61 to 2.49), postoperative bleeding (odds ratio 1.35, 1.09 to 1.68) and septicemia (odds ratio 2.43, 1.85 to 3.21) without significant differences in overall mortality. Disability severity was positively correlated with postoperative septicemia risk. Medical service use was also significantly higher in surgical patients with intellectual disability.Intellectual disability significantly increases the risk of overall major complications after major surgery. Our findings show a need for integrated and revised protocols for postoperative management to improve care for intellectually disabled surgical patients