Initial and subsequent dosing of rectal acetaminophen in children: a 24-hour pharmacokinetic study of new dose recommendations.

BACKGROUND: Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation. METHODS: Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. RESULTS: All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. CONCLUSIONS: A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.

Latex allergy in children: diagnosis and management.

Latex allergy is an increasingly common condition, in both children and health care workers who provide care for them. Subpopulations at particular risk include children with spina bifida, children undergoing multiple surgical procedures, and health care workers in the operating theatre. Chemical additives in latex gloves can cause an irritant or allergic contact dermatitis. Latex proteins are responsible for most of the immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from rhinitis, conjunctivitis and urticaria to anaphylaxis and death. A latex-directed history is the primary method of identifying latex sensitivity, although both skin and serum testing is available and increasingly accurate. (Latex avoidance should be used in all individuals with a positive skin or blood test or a positive history). The most important preventive measure for patients with or at risk for latex allergy is minimizing direct patient exposure to latex products, most notably latex gloves. Recent operating room studies indicate simple preventive measures can dramatically reduce intraoperative reactions. Preoperative prophylaxis with antihistamines and steroids have not been shown to be necessary or effective. Treatment of an allergic reaction begins with immediate removal of any identified source of latex in direct patient contact. Treatment is similar to anaphylaxis from other causes, and may require the use of epinephrine. Everyone caring for the patient at risk for latex allergy must be involved in making their medical environment safe.

Premedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate.

UNLABELLED: We assessed the safety and efficacy of oral transmucosal fentanyl citrate (Fentanyl Oralet; Abbott Laboratories, Abbott Park, IL), administered preoperatively to provide both preoperative sedation and postoperative analgesia, in a randomized, double-blind, placebo-controlled study in 40 children, 2-10 yr of age, scheduled for tonsillectomy. In the preoperative holding area, one group (Group O) received Fentanyl Oralet (fentanyl 10-15 micrograms/kg), and the other (Group IV) received only the candy matrix. Patients in Group O received an i.v. injection of saline, and those in Group IV received an i.v. injection of fentanyl (2 micrograms/kg) after removal of the first tonsil. Except for the opioid, patients received a standard anesthetic. Preoperative sedation and cooperation were assessed. Postoperative pain was evaluated using an objective pain scale. Patients in Group O were more sedated but no more cooperative at the induction of anesthesia compared with those in Group IV. No patient vomited preoperatively or experienced preoperative or postoperative desaturation. Time to postanesthesia care unit (PACU) discharge was not different between groups. There was no significant difference in the number of patients requiring morphine in the PACU (6 of 21 in Group O versus 10 of 19 in Group IV). Plasma fentanyl concentrations were not a reliable indicator of the need for postoperative morphine. Among the patients who required morphine postoperatively, there was an 11-fold variation in plasma fentanyl concentrations at the time of morphine administration. Derived pharmacokinetic parameters were similar to those previously reported in children; bioavailability of the fentanyl in Fentanyl Oralet was 0.33. We conclude that premedication with Fentanyl Oralet did not differ with i.v. fentanyl in regard to the induction of anesthesia and postoperative analgesia. IMPLICATIONS: In this double-blind, randomized study, we studied the efficacy of Fentanyl Oralet (10-15 micrograms/kg) preoperatively for providing postoperative analgesia in children undergoing tonsillectomy. We found no incidence of preoperative desaturation or vomiting in any patient. This is in contrast to other studies, in which there was a longer time interval between Fentanyl Oralet completion and induction of anesthesia. The bio-availability of the fentanyl in Fentanyl Oralet was estimated to be 33%, which is less than that reported in adults (approximately 50%). There was no difference in postoperative opioid requirements between patients who received 2 micrograms/kg of fentanyl i.v. and those who received Fentanyl Oralet.

Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations.

BACKGROUND: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. METHODS: Children (n = 28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. RESULTS: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 microg/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml x kg(-1) x min(-1). Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. CONCLUSIONS: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 microg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

Do latex precautions in children with myelodysplasia reduce intraoperative allergic reactions?

Children with myelodysplasia have an increased incidence of latex allergy, which can lead to severe intraoperative allergic reactions. Despite widespread recommendations to avoid intraoperative latex exposure, little evidence exists to support the efficacy of this practice. We examined the incidence of intraoperative allergic reactions in children with myelodysplasia who underwent 1,025 operations in a 36-month period before and after institution of a standardized latex-avoidance protocol. Risk factors for an intraoperative reaction were found to be a history of latex allergy (p = 0.001) and surgery performed before institution of the latex-avoidance protocol (p = 0.01). The estimate of increased risk for allergic reaction was 3.09 times higher in cases performed without latex avoidance. Recognized violation of the protocol after its institution led to severe allergic reactions in three patients. Our experience suggests that a latex-avoidance protocol reduces intraoperative allergic reactions in children with myelodysplasia. Development of severe allergic reactions with violation of the protocol reinforces the importance of vigilance on the part of all operating room personnel in its implementation.

Ventilatory support for infants in emergency and in the intensive care unit.

Pediatric anesthesia and intensive care management has improved dramatically over the past two decades. Improved understanding of the pathophysiology underlying newborn surgical emergencies, new medications and new modes of ventilatory support have all contributed to better patient outcome. The authors have reviewed the anatomy and physiology of the infant airway, indications for and principles of endotracheal intubation, the management of newborn surgical emergencies, indications for post-operative ventilatory support, different modes of mechanical ventilation available, complications of mechanical ventilation with weaning parameters and extubation criteria. The introduction of nitric oxide and the implications of extracorpreal membrane oxygenation in the management of newborn emergency refractory to conventional ventilation are discussed.

Effect on moisture permeability of typewriting on unit dose package surfaces.

The effects of typewriting on labels of two unit dose packages with respect to moisture permeability were examined. Using an electric typewriter, a standard label format was imprinted on two different types of class A unit dose packages: (1) a heat-sealed paper-backed foil and cellofilm strip pouch, and (2) a copolyester and polyethylene multiple-cup blister with a heat-sealed paper-backed foil and cellofilm cover. The labels were typed at various typing-element impact settings. The official USP test for water permeation was then performed on typed packages and untyped control packages. The original untyped packages were confirmed to be USP class A quality. The packages for which successively harder impact settings were used showed a corresponding increase in moisture permeability. This resulted in a lowering of USP package ratings from class A to class B and D, some of which would be unsuitable for use in any unit dose system under current FDA repackaging standards. Typing directly onto the label of a unit dose package before it is sealed will most likely damage the package and possibly make it unfit for use. Pharmacists who must type labels for the unit dose packages studied should use the lowest possible typewriter impact setting and test for damage using the USP moisture-permeation test.

Effect of pharmacist intervention on the use of serum drug assays.

The results of an investigation to (1) evaluate the use of serum drug assays (SDAs), (2) study the influence of clinical pharmacist monitoring and educational programs on SDA use, and (3) perform drug-related patient-care evaluations for the medical audit committee are reported. The components of the five-month study were a retrospective audit, education of physicians prescribing SDAs, and a concurrent reaudit. The four SDAs audited were digoxin, theophylline, gentamicin, and phenytoin. Criteria for appropriate use were defined by the audit committee and a clinical pharmacist. The criteria specified the indication for each drug, performance data, and dosage adjustments with SDA results. The clinical pharmacist presented two housestaff conferences on the appropriate use of SDAs and distributed educational materials to the attending physicians. An SDA report form was completed each time an SDA was ordered, and, whenever possible, the pharmacist met with the prescribing physician. Appropriate overall use of SDAs increased significantly (p less than 0.05). A significant improvement (p less than 0.05) was noted for each of the criteria. An estimated $2500 in patient charges was saved during the study; the cost of the clinical pharmacist's time was approximately $260. The authors concluded that clinical pharmacists, in conjunction with patient-care evaluations, can provide a cost-effective service in improving therapeutic patient monitoring based on SDA results.