Monitoring blood levels of selected drugs. Remember to factor in the many confounding variables.

Appropriate use of various pharmacologic agents involves not only awareness of therapeutic indications and side effects but also familiarity with clinical use and timing of blood level monitoring. The effective as well as the toxic level of antiepileptic drugs varies widely among patients, so the patient's response is more important than the serum drug level. These agents may interact with other disease states, other drugs, and even other antiepileptic agents. Because of digoxin's long half-life and the effect of physical exercise on serum concentration, the timing of serum collection is important. The usefulness of measuring amiodarone serum concentrations is controversial, but findings may help identify patients at risk for side effects related to the drug. Procainamide has a very short half-life and concentrations change over a short period, so blood levels of this agent should be measured before administration of a dose. The dose of levothyroxine required to restore a normal thyroid hormone level varies with age, coexistent conditions, and use of other medications. After the appropriate dose is determined, follow-up monitoring yearly is necessary (more often in the elderly). Efficacy and toxicity of theophylline are directly related to serum concentrations, and a reduced target level of 5 to 15 micrograms/mL has recently been suggested. Proper monitoring is important, because metabolic changes and drug interactions can cause either subtherapeutic or toxic levels.

Current patterns of prescribing and administering morphine in trauma patients.

We attempted to characterize the current prescribing practices and administration patterns for intravenous intermittent morphine in trauma patients in a multicenter, open prospective, observational study. The subjects were 141 patients admitted to the surgical intensive care units (ICU) of five United States trauma centers within 12 hours of injury who received intermittent intravenous morphine for pain relief. The study was conducted from April 15, 1992, to February 15, 1993. Data obtained during the first 32 hours of the ICU stay included morphine regimen, doses administered, and time between doses. One hundred sixty-one orders were prescribed by surgeons. The most frequently ordered dose was 2-4 mg and the most frequently ordered interval was every hour as necessary. There was no relationship between the severity of injury and the minimum dose ordered. During the 492 nursing shifts studied, 1257 doses were administered. Of these, 44% were at or below the minimum amount prescribed by the surgeons. Thirty-three percent of the patients received a dose at an interval of more than 3 hours. We concluded that small amounts of narcotic analgesics are given to severely injured patients, and amount ordered is not affected by the severity of injury.

Comparison of sprinkle versus syrup formulations of valproate for bioavailability, tolerance, and preference.

We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability = 1.02), but absorption was slower (time to maximum concentration = 4.2 vs 0.9 hour; p less than 0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p less than 0.01). Sprinkle was preferred by 9 of the 12 parents because of east of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.