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Michael J Avram

Publications and source records attributed to Michael J Avram.

26 records · Page 2Linked to original sources
PubMed2002

Uptake pharmacokinetics of the Fentanyl Oralet in children scheduled for central venous access removal: implications for the timing of initiating painful procedures.

BACKGROUND: The Fentanyl Oralet (Abbott Laboratories, Abbott Park, IL, USA) is an oral transmucosal drug delivery system. We previously examined pharmacokinetic parameters of children who had completed consumption of the Fentanyl Oralet. The present study was designed to clarify pharmacokinetic parameters during the consumption phase to determine if there is an optimal administration time before painful procedures. METHODS: Patients, aged 3-10 years, who were scheduled for elective removal of central venous access devices under general anaesthesia, received a Fentanyl Oralet (fentanyl 10-15 microg x kg(-1)). Plasma fentanyl concentrations were measured by radioimmunoassay. Data from blood samples obtained during and after consumption of the Fentanyl Oralet from 17 patients in the present study were combined with data from our previous study to better characterize both the consumption and postconsumption concentration versus time profiles. RESULTS: Estimated fentanyl bioavailability (mean +/- SD) was low (36.1 +/- 0.4%), as were peak plasma concentrations (1.03 +/- 0.31 ng.ml-1), suggesting that many children swallowed a large fraction of the dose. This led to a relatively late and variable peak concentration time of 53 +/- 40 min. In addition, because of the apparently large degree of gastrointestinal absorption, concentration versus time curves were wide and flat. CONCLUSIONS: The wide and flat concentration versus time profile may allow flexibility in the timing of a painful procedure following Fentanyl Oralet administration. However, the variability of the time to peak concentration makes it difficult to suggest a minimum interval between Fentanyl Oralet consumption and the start of a painful procedure.

Administration, Buccal↗
PubMed2002

Age-stratified pharmacokinetics of ketorolac tromethamine in pediatric surgical patients.

UNLABELLED: Published data suggest that ketorolac pharmacokinetics are different in children than in adults. We sought to better characterize ketorolac pharmacokinetics in children. Thirty-six children, aged 1-16 yr, were stratified into four age groups: 1-3 yr, 4-7 yr, 8-11 yr, and 12-16 yr. Each child received 0.5 mg/kg of ketorolac tromethamine IV after completion of elective surgery. A maximum of 16 venous blood samples (mean, 13 +/- 2) were collected at predetermined times up to 10 h after drug administration. Plasma ketorolac concentrations were measured by high-performance liquid chromatography after solid-phase extraction. Individual concentration-versus-time relationships were best fit to a two-compartment pharmacokinetic model by using SAAM II. Body weight-normalized pharmacokinetic variables did not differ among the age groups and were similar to those reported for adults, including a volume of distribution at steady state of 113 +/- 33 mL/kg (mean +/- SD) and an elimination clearance of 0.57 +/- 0.17 mL x min(-1) x kg(-1). Our study demonstrates that a single dose of ketorolac (0.5 mg/kg) results in plasma concentrations in the adult therapeutic concentration range for 6 h in most children. Our data provide no evidence that children require either larger weight-adjusted doses or shorter dosing intervals than adults to provide similar plasma drug concentrations. IMPLICATIONS: The literature suggests that ketorolac disposition differs between children and adults. We characterized ketorolac pharmacokinetics in 36 children. Body weight-normalized two-compartment pharmacokinetic variables did not differ among pediatric patients <17 yr old and were similar to adult values.

Adolescent↗
PubMed2002

The use of neuromuscular blocking drugs in adult cardiac surgery: results of a national postal survey.

UNLABELLED: Available data suggest that the choice of neuromuscular blocking drugs (NMBDs) can influence early clinical recovery of the fast-track cardiac surgical patient. The aim of this study was to use a survey tool to determine practice patterns of anesthesiologists for the use of NMBDs in the cardiac surgical setting. We mailed a survey to one third of the 3295 active members of the Society of Cardiovascular Anesthesiologists. A follow-up letter and survey were sent to each individual who did not respond to the initial mailing. After the second mailing, 459 surveys were returned, yielding a response rate of 43%. Pancuronium was listed as the primary NMBD used in the majority of patients undergoing cardiopulmonary bypass (69%) and off-pump (41%) procedures. Only 28% of respondents routinely used a peripheral nerve stimulator to monitor neuromuscular blockade in the operating room. Residual neuromuscular blockade was routinely reversed before tracheal extubation by only 9% of cardiac anesthesiologists. This survey demonstrates that long-acting NMBDs are often administered to fast-track cardiac patients. Peripheral nerve stimulator monitoring is rarely used in the operating room or intensive care unit, and reversal drugs (anticholinesterases) are infrequently administered in the postoperative period. IMPLICATIONS: This postal survey of cardiac anesthesiologists demonstrates that long-acting muscle relaxants are frequently administered to fast-track cardiac surgical patients. Neuromuscular blockade is rarely monitored or reversed in this patient population.

Adult↗
PubMed2002

Impact of shorter-acting neuromuscular blocking agents on fast-track recovery of the cardiac surgical patient.

BACKGROUND: Residual paralysis associated with the use of long-acting muscle relaxants can delay recovery from anesthesia and surgery. The authors tested the hypothesis that use of shorter-acting neuromuscular blocking agents is associated with reductions in tracheal extubation times and intensive care unit (ICU) length of stay in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: One hundred ten patients scheduled for elective coronary artery bypass grafting or single valve surgery were randomized prospectively to receive either pancuronium or rocuronium intraoperatively. Anesthetic management and muscle relaxant maintenance dosing were standardized. In the ICU, the time required to wean ventilatory support, the duration of tracheal intubation, and length of stay were recorded. Subjects were asked to quantify generalized muscle weakness as they awakened in the ICU and again after tracheal extubation. RESULTS: Complete data were collected on 51 patients in the pancuronium group and 52 patients in the rocuronium group. No differences were found between the groups in anesthetic, surgical, or ICU management. Significant increases in the duration of weaning of ventilatory support were observed in patients who received pancuronium (median, 180 min; range, 50-780 min) compared with the rocuronium group (median, 110 min; range, 45-250 min). Tracheal extubation was significantly delayed in the pancuronium group (median, 500 min; range, 240-1,305 min) compared with the rocuronium group (median, 350 min; range, 210-1,140 min). Subjects in the pancuronium group experienced more mild to severe weakness in the ICU. However, the choice of muscle relaxant did not influence ICU length of stay. CONCLUSION: The use of shorter-acting neuromuscular blocking agents in patients undergoing cardiac surgery with cardiopulmonary bypass is associated with reductions in tracheal extubation times and symptoms of residual paresis.

Adult↗
PubMed2002

Gastric emptying of water in term pregnancy.

BACKGROUND: Healthy nonpregnant patients may ingest clear liquids until 2 h before induction of anesthesia without adversely affecting gastric volume. The purpose of this study was to compare gastric emptying in term, nonlaboring pregnant women after ingestion of 50 ml water (control) with that after ingestion of 300 ml water. METHODS: Gastric emptying was assessed in healthy, nonobese, term pregnant volunteers using both serial gastric ultrasound examinations (n = 9) and acetaminophen absorption (n = 11) in a crossover study design. After an overnight fast, volunteers ingested 1.5 g acetaminophen and 50 or 300 ml water (assigned in random order) on two occasions separated by at least 2 days. Serial gastric antrum cross-sectional areas were determined using gastric ultrasound imaging, and the half-time to gastric emptying was calculated. Serial plasma acetaminophen concentrations were measured. Areas under the plasma acetaminophen concentration versus time curve, peak concentrations, and time to peak concentration for 50- and 300-ml ingestions were compared. RESULTS: Gastric emptying half-time was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (24 +/- 6 vs. 33 +/- 8 min). There were no differences in acetaminophen areas under the curve at 60, 90, or 120 min, or in acetaminophen peak concentration. Time to peak concentration of acetaminophen was significantly shorter after ingestion of 300 ml water than after ingestion of 50 ml (25 +/- 12 vs. 41 +/- 19 min). CONCLUSIONS: Gastric emptying in healthy, term, nonobese, nonlaboring pregnant women is not delayed after ingestion of 300 ml water compared with that after an overnight fast.

Acetaminophen↗
PubMed2002

The concordance of early antipyrine and thiopental distribution kinetics.

Studies of factors affecting the initial disposition of drugs with a rapid onset of effect following i.v. administration have used antipyrine as a surrogate for lipophilic drugs because it lacks cardiovascular effects. The present study tested the assumption that antipyrine is a useful surrogate for the flow-dependent tissue distribution of the lipophilic drug thiopental by comparing the recirculatory pharmacokinetic models of antipyrine and thiopental disposition after concomitant administration to five dogs anesthetized with 1.5% halothane. The pharmacokinetics of indocyanine green, a marker of the intravascular behavior of antipyrine and thiopental, and antipyrine in these dogs was nearly identical to that described previously in dogs anesthetized with 1.5% halothane but not given thiopental. The total volume of distribution of the highly lipophilic drug thiopental was more than 60% larger than that of antipyrine, 53 versus 33 liters, respectively. Nonetheless, the initial distribution kinetics of the two drugs, including the pulmonary tissue volume and the volume of the nondistributive pathway as well as the clearance to it, were nearly identical. As a result, the fraction of cardiac output involved in distribution of the two drugs to peripheral tissues was similarly identical, although the distribution of cardiac output between clearance to the rapidly equilibrating tissues and clearance to the slowly equilibrating tissues differed slightly. This study validates the assumption that antipyrine is a useful surrogate for lipophilic drugs in pharmacokinetic studies in which physiologic stability is desirable to meet the assumption of system stationarity.

Animals↗