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Biomedical subjects

T H Stanley

Publications and source records attributed to T H Stanley.

At least 19 recordsLinked to original sources
PubMed1992

The history and development of the fentanyl series.

In the last two decades, opioid analgesics have assumed an important place in general anesthetic practice in the United States. Part of the reason for this has been the introduction of the potent new agonists fentanyl, sufentanil, and alfentanil. Because of problems with morphine-oxygen anesthesia (incomplete amnesia, occasional histamine-related reaction, marked increases in intra- and postoperative respiratory depression), a suitable alternative was sought but not found among existing opioids. A breakthrough came in 1960, when fentanyl was synthesized, laying the foundation for a better understanding of the structure-activity relationships of narcotic analgesics and stimulating interest in developing compounds with even greater potency and safety margins. Investigators interested in opioid anesthesia began to study fentanyl in animals and then in humans. Fentanyl (50-100 micrograms/kg) with oxygen (100%) was evaluated as an anesthetic in patients undergoing mitral valve and coronary artery surgery. Changes in cardiovascular dynamics with induction doses ranging from 8 to 30 micrograms/kg consisted of small decreases in heart rate and arterial blood pressure. All other cardiovascular variables studied, including cardiac output, remained unchanged, even with additional doses up to 100 micrograms/kg. It was determined that fentanyl had use as a narcotic anesthetic, despite its potential for cardiovascular depression and stimulation, respiratory depression, muscle rigidity, and, occasionally, incomplete anesthesia. Since the introduction of fentanyl, two other potent synthetic opioids have been introduced into clinical practice--sufentanil and alfentanil.

Combined Modality Therapy↗
PubMed1992

The antiemetic effect of lorazepam after outpatient strabismus surgery in children.

The high incidence of postoperative emesis after strabismus surgery in pediatric outpatients can be reduced by the prophylactic administration of droperidol 75 micrograms/kg intravenously. However, this may be associated with profound sedation, delayed discharge, dysphoria, agitation, and extrapyramidal symptoms in this population. Because lorazepam used as an antiemetic in children during chemotherapy decreased the incidence of nausea and vomiting, we compared the antiemetic effects of lorazepam and droperidol in a randomized, double-blind, placebo-controlled study of 129 healthy children undergoing surgical correction of strabismus. The children, aged 1-13 yr, were randomly allocated into three groups. The children in group 1 received droperidol 75 micrograms/kg intravenously; those in group 2 received lorazepam 10 micrograms/kg intravenously; and those in group 3 received placebo. Anesthesia consisted of halothane, nitrous oxide in oxygen, and atracurium. Study drugs were administered intravenously after induction of anesthesia but before surgery. In children 3-13 yr old, administration of either lorazepam or droperidol was associated with a lower (P < 0.024) incidence of postoperative vomiting. There was no difference between the antiemetic effect of lorazepam and that of droperidol. The incidence of postoperative agitation was greater in the droperidol group (P < 0.001) than in the lorazepam and placebo groups. Postdischarge vomiting was less (P < 0.009) in children younger than 3 yr of age. Lorazepam, similar to droperidol, has an antiemetic effect in outpatient children 3-13 yr old undergoing strabismus correction, but it is associated with less postoperative agitation than is droperidol.

Adolescent↗
PubMed1991

Oral transmucosal fentanyl citrate for analgesia and sedation in the emergency department.

STUDY OBJECTIVE: To evaluate the safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a noninvasive method of providing analgesia and sedation for patients in the emergency department. DESIGN: Prospective, nonblinded. SETTING: ED of a tertiary care university hospital. TYPE OF PARTICIPANTS: Ten patients, 6 to 34 years old, with acute painful conditions requiring treatment in the ED. INTERVENTIONS: Premedication with OTFC and local anesthetic prior to incision or wound closure. MEASUREMENTS AND MAIN RESULTS: Pain and activity (sedation) scores, vital signs (including systolic and diastolic arterial blood pressures, heart and respiratory rates, and pulse oximetry-determined oxygen saturation) were measured before and at two- to ten-minute intervals during and after OTFC consumption. All patients accepted OTFC. Patients received an average of 13.7 +/- 2.5 micrograms/kg of fentanyl citrate in 11.8 +/- 6.8 minutes. Decreases in pain were reported in two patients in two minutes and by all patients 14 minutes after beginning OTFC consumption. Sixty percent of patients became drowsy or sedated 12 to 30 minutes after beginning OTFC. Vital signs and oxygen saturation changes were small and not clinically significant. The most important side effects were pruritus (30%), nausea (20%), and dizziness and dry mouth (40%). All were considered mild and not disturbing, although one patient required post-procedure antiemetic therapy for recurrent vomiting. The mean time to discharge from the ED was 139 +/- 54 minutes after receiving OTFC. CONCLUSION: OTFC may be useful in providing rapid, noninvasive analgesia and sedation in the ED and deserves further evaluation.

Administration, Oral↗
PubMed1991

Respiratory effects of clonidine alone and combined with morphine, in humans.

Because only limited and controversial data exist concerning the respiratory effects of clonidine in humans, the authors evaluated the respiratory effects of clonidine alone and in combination with morphine, in 12 healthy adult males. Subjects received clonidine (0.3-0.4 mg orally), morphine (0.21 mg/kg intramuscularly), or the same doses of the two drugs combined, at three separate sessions in a randomized fashion. The study was balanced for all possible sequences of drug administration. Blood pressure, heart rate, hemoglobin oxygen saturation via finger pulse oximetry, and ventilatory and occlusion pressure responses to CO2 were obtained before and 20, 40, 60, 90, 120, 180, 240, 300, and 360 min after administration of drug or drug combination. Systolic blood pressure decreased significantly only in the clonidine and clonidine plus morphine groups (P less than 0.05). Hemoglobin oxygen saturation decreased by a statistically significant (P less than 0.05), though clinically minor, degree only in the morphine or morphine plus clonidine groups. Clonidine alone did not depress the slope of either the ventilatory or the occlusion pressure response to CO2. In addition, clonidine did not significantly worsen morphine-induced depression of the slope of the ventilatory and occlusion pressure responses in the drug combination group. Both the ventilatory and occlusion pressure responses to CO2 were shifted to the right in all three drug groups (P less than 0.05) but were shifted to a significantly lesser degree by clonidine alone than by morphine and morphine plus clonidine. In healthy young adult males, clonidine alone produces little respiratory depression and does not significantly potentiate morphine-induced respiratory depression.

Adolescent↗
PubMed1991

Absorption and bioavailability of oral transmucosal fentanyl citrate.

Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys.

To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1991

Induction of anesthesia in children following administration of methohexital into the sigmoid colon.

The authors evaluated the sigmoidal administration of methohexital, the effect of methohexital concentration (1% versus 2%), the effect of dosage (25 mg/kg versus 15 mg/kg) on sleep-success rate, administration - sleep time, recovery time and the effect of aspirating the residual methohexital on recovery time. The study demonstrated that both 1% solution and 25 mg/kg of sigmoidal methohexital were independently associated with significantly higher sleep success rate and faster onset of sleep compared with 2% and 15 mg/kg of sigmoidal methohexital solution respectively. The recovery time was significantly affected by the dose of methohexital and was not significantly affected by the concentration of methohexital solution. Aspiration of the residual methohexital did not significantly affect the recovery time.

Catheterization↗
PubMed1990

Oral transmucosal fentanyl citrate for premedication in paediatric outpatients.

Two doses (10-15 micrograms.kg-1, Group I, and 15-20 micrograms.kg-1, Group II) of oral transmucosal fentanyl citrate (OTFC) plus a placebo (Group III) were evaluated for premedication in 105 healthy children, aged 2 to 13 yr, undergoing short (less than 1 hr) operations in the hospital short-stay unit. The study was randomized and double-blinded and 91 of the 105 children also received droperidol, 25 micrograms.kg-1 IV, after induction of anaesthesia with halothane and N2O in oxygen. Both doses of OTFC produced significantly greater sedation (first present at 20 min) and anxiolysis (first present in Group I at 40 min) than the placebo. Recovery times were similar in the three groups and analgesic requirements in the recovery room were significantly lower in Group I than Group III. Both OTFC groups took longer to tolerate oral fluids in the postoperative discharge unit than the placebo group and this caused patients in Group I to have a delayed discharge from the hospital compared to Group III. Preoperative pruritus occurred significantly more frequently in Groups I and II (58 and 76 per cent, respectively) than Group III (23 per cent). Although the incidences of nausea and vomiting tended to be slightly higher in the OTFC groups in the preoperative holding and postoperative discharge units, the differences among the groups were not statistically significant. Likewise droperidol did not reduce the incidence of postoperative nausea or vomiting. The data indicate that OTFC may be a safe and effective premedicant in paediatric patients having short operations but delays discharge from the hospital (by 30-50 min) by delaying the time patients tolerate fluids early after operation.

Administration, Oral↗
PubMed1990

Cardiovascular effects of large doses of pentamorphone in the dog.

The cardiovascular effects of large doses of pentamorphone were evaluated in nine mongrel dogs basally anesthetized with sodium thiopental, 25 to 30 mg/kg, intravenously. All dogs were mechanically ventilated with 100% oxygen, and the PaCO2 was maintained between 35 and 40 mm Hg. Mean arterial pressure (MAP), central venous pressure, heart rate (HR), cardiac output (CO), pulmonary artery pressure, and pulmonary artery occluded pressure were measured, and stroke volume and systemic and pulmonary vascular resistances were calculated. Baseline measurements were obtained, then pentamorphone, 10 micrograms/mL, was given as an intravenous infusion at 2.5 micrograms/kg/min. Additional data were obtained after infusion of 25, 50, 75, 100, 125, 150, 200, 250, 300, and 350 micrograms/kg of pentamorphone. The inspired gases were then changed to 50% nitrous oxide in oxygen, and after a 20-minute equilibration period, an additional set of data was collected. Pentamorphone, 25 micrograms/kg, decreased HR 50%, MAP 65%, and CO 54%. No further changes in any measured or calculated variables were observed with additional doses of pentamorphone. The addition of 50% nitrous oxide to the inspired gas mixture had no effect on any measured or calculated hemodynamic variable. The minimal hemodynamic effects of pentamorphone in the dog suggest that further investigation into its use as an anesthetic is warranted.

Analysis of Variance↗
PubMed1990

Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy.

The authors evaluated the effect of transdermal scopolamine on the incidence of postoperative nausea, retching, and vomiting after outpatient laparoscopy in a double-blind, placebo-controlled study. A Band-Aid-like patch containing either scopolamine or placebo was placed behind the ear the night before surgery. Anesthesia was induced with fentanyl (0.5-2 micrograms/kg iv), thiopental (3-5 mg/kg iv), and succinylcholine (1-1.5 mg/kg iv) and maintained with isoflurane (0.2-2%) and nitrous oxide (60%) in oxygen. Scopolamine-treated patients had less nausea, retching, and vomiting compared with placebo-treated patients (P = 0.0029). Severe nausea and/or vomiting was present in 62% of the placebo group but only 37% of those getting the scopolamine patch. Repeated episodes of retching and vomiting were also less frequent in the scopolamine group compared with the placebo group (23% vs. 41%; P = 0.0213) as was the need for additional antiemetic therapy (13% vs. 32%; P = 0.0013). Patients in the scopolamine group were also discharged from the hospital sooner (4 +/- 1.3 vs. 4.5 +/- 1.5 h; P = 0.0487). Side effects were more frequent among those patients treated with the scopolamine patch (91% vs. 45%; P less than 0.05) but were not troublesome. The authors conclude that transdermal scopolamine is a safe and effective antiemetic for outpatients undergoing laparoscopy.

Administration, Cutaneous↗
PubMed1990

Frequent hypoxemia and apnea after sedation with midazolam and fentanyl.

More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.

Adolescent↗
PubMed1990

Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil.

The magnitude and duration of analgesia and respiratory depression induced by fentanyl (1.0, 2.0, and 4.0 micrograms/kg) and sufentanil (0.1, 0.2, and 0.4 microgram/kg) after intravenous administration over 30 s were measured in 30 healthy young adult male volunteers divided into three groups and studied in a double-blind, randomized fashion. Each volunteer received one dose of fentanyl or sufentanil and no sooner than 48 h later, the corresponding equipotent dose of the other opioid. End-tidal CO2 and ventilatory and occlusion pressure responses to CO2 rebreathing were used to measure drug-induced respiratory effects. Analgesic effects were assessed by changes in the pain threshold to electric shock applied to the forearm. Plasma levels of fentanyl and sufentanil were measured by radioimmunoassay. Testing and sampling intervals were 5, 30, 60, 90, 120, 240, 300, and 360 min after drug administration. The magnitude and duration of depression of the ventilatory and occlusion pressure response were significantly less with sufentanil compared with fentanyl, irrespective of dose. Ventilatory and occlusion pressure responses returned to control values by 30 and 30 min, respectively, after sufentanil and by 240 and 120 min, respectively, after fentanyl. Statistically significant elevations of the pain threshold were, however, greater and longer lasting after sufentanil compared with fentanyl. Pain threshold returned to control values 180 min after sufentanil but only 90 min after fentanyl. These results suggest that sufentanil may provide better patient comfort with less respiratory depression than does fentanyl.

Adolescent↗
PubMed1990

Rectal methohexital: concentration and length of the rectal catheters.

In the study, the authors evaluated the concentration of rectal methohexital (1% vs 10%) and the length of the rectal catheter (3.8 vs 12.7 cm), on sleep-success rate, administration-sleep time, methohexital plasma concentrations, and recovery time in 85 healthy children scheduled for elective ophthalmic or ear, nose, or throat operations lasting approximately 1 h. At a dose of 25 mg/kg, the 1% solution of rectal methohexital was associated with a significant (P less than 0.05) higher sleep-success rate (95% vs 70%), shorter administration-sleep time (5.7 +/- 1.9 vs 7.0 +/- 2.0 min), higher methohexital plasma concentrations at 20 min (6.5 vs 4.7 ng/mL) and at 30 min (5.3 vs 3.7 ng/mL), and prolonged recovery time (53.2 +/- 31.1 vs 32.4 +/- 18.5 min). The length of the rectal catheters did not significantly affect sleep-success rate, administration-sleep time, methohexital plasma concentrations, or recovery time. The use of 25 mg/kg of 1% rectal methohexital solution to induce anesthesia in children is superior to the use of 25 mg/kg of 10% methohexital solution for induction of anesthesia in children, particularly in operations 1 h or longer in duration.

Anesthesia Recovery Period↗
PubMed1989

Comparison of oral transmucosal fentanyl citrate and an oral solution of meperidine, diazepam, and atropine for premedication in children.

The safety and efficacy of premedication with oral transmucosal fentanyl citrate (OTFC) was compared with that of an orally administered solution of meperidine, diazepam, and atropine and no premedication in 59 children about to undergo elective operations. The patients were randomly assigned to receive no premedication (n = 19); 0.25 ml/kg of the oral solution (containing meperidine, 1.5 mg/kg, diazepam, 0.2 mg/kg, and atropine, 0.02 mg/kg, n = 20); or OTFC (15-20 micrograms/kg, n = 20). Children had activity (sedation) and anxiety scores, vital signs (including systolic and diastolic arterial blood pressures and heart and respiratory rates) and pulse oximetry determined oxygen saturation measured before and at 10-min intervals after premedication until they were taken to the operating room. Quality of induction and recovery was evaluated using scoring schedules; recovery times were measured and side effects noted. OTFC was readily accepted and provided significant reductions in preoperative activity (sedation) and anxiety starting after 30 min. After OTFC, sedation and anxiolysis were significantly greater than in children having no premedication but similar to children having the oral solution for premedication. Vital signs and oxygen saturations remained unchanged preoperatively in all groups. Induction and recovery evaluations and recovery times were similar in the three groups, although children having OTFC had the lowest requirements for narcotics in the recovery room. OTFC caused an 80% incidence of mild preoperative facial pruritus and a higher overall incidence of postoperative vomiting (37%) than premedication with the oral solution (5%) or no premedication (18%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗