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Biomedical subjects

T H Stanley

Publications and source records attributed to T H Stanley.

At least 37 records · Page 2Linked to original sources
PubMed1993

How do anesthesiologists select patients when introducing a new drug into practice?

As part of the marketing strategy for the anesthetic drug propofol (Diprivan), Stuart Pharmaceuticals began a Phase IV postmarketing study soon after the drug received Food and Drug Administration approval in 1989. We used data from this study to test the hypothesis that anesthesiologists would initially use propofol for young, relatively healthy patients and then, with experience, for older, sicker patients. The Phase IV study involved 1722 institutions, 1819 anesthesiologists, and 25,981 patients. The study incorporated three sequential steps, each to be tested in five patients. In Step 1, propofol was used for induction only; in Step 2, for induction and maintenance of anesthesia by intermittent injection; and, in Step 3, for induction and maintenance by continuous infusion. Inclusion criteria were age 18-80 yr and ASA physical status I-III. Exclusion criteria were continuing pregnancy and a previous adverse anesthetic experience. Physicians used standardized data collection forms to voluntarily compile detailed demographic, perioperative, and outcome variables for patients. Data were then evaluated by an independent, multicenter team of seven anesthesiologists and three epidemiologists to determine whether the first two patients selected to participate in each step (Patients 1 and 2, 6 and 7, and 11 and 12) were less sick, younger, or undergoing less invasive or shorter procedures than patients enrolled later in the same steps (Patients 4 and 5, 9 and 10, and 14 and 15). Physicians gave propofol first to patients with fewer concurrent diseases than are found in the general population (10% were hypertensive versus 16%; 3% were diabetic versus 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Phase IV study of propofol: validation of the data set.

In 1989-1990, Stuart Pharmaceuticals conducted a Phase IV study of propofol on over 26,000 patients, later making the large data base available to a team of epidemiologists and anesthesiologists for analysis. We now describe the process of verifying the data to provide a sound basis for further analyses. Original data were collected by 1819 physicians at 1761 hospitals. In that study, anesthesia was induced by bolus injection of propofol and was maintained by inhaled drug and N2O-O2 (Step 1), or by propofol (either intermittent bolus injection [Step 2] or continuous infusion [Step 3]) and N2O-O2. Forty-six recorded variables described history, physical examination, course and quality of anesthesia and recovery, and adverse events. Data were scrutinized for inaccuracy or bias regarding adverse events, completeness of data, data entry, and violations of the study protocol. The initial data set pertained to 26,841 patients (10,698, Step 1; 8886, Step 2; and 7257, Step 3). Because we excluded data if 25% of the items were missing from the data set, 3.2% of the case reports were eliminated: the final data set used for subsequent analyses contained 25,981 patients (10,184, Step 1; 8672, Step 2; and 7125, Step 3). Inaccuracy of data entry was not excessive, and violations of study protocol were less frequent than in similar studies. The nature and frequency of adverse events were similar to those reported in Phase II and III clinical trials of propofol. Analysis showed that missing data occurred randomly and did not introduce obvious bias. We conclude that the data set was valid and most likely represents perioperative events occurring in similar patients; that Phase IV studies can be valuable because of the range of patients studied and the ability to detect even rare events; and that future Phase IV studies could be improved by more efficient design of data collection forms for both hypotheses to be tested and the entry of data onto forms.

Adolescent↗
PubMed1993

The role of pharmacoepidemiology research in postmarketing surveillance and anesthesia practice/critical care medicine.

Despite tremendous efforts to ensure the safety and effectiveness of newly marketed medications, a number of these have had significant problems after introduction of the drug to the market. Such problems highlight the practical limitations of clinical trials performed to obtain FDA approval for marketing. Pharmacoepidemiology research methodologies provide a powerful mechanism for exploring the determinants of drug safety and effectiveness in broad-based populations and can serve as a scientific foundation for outcome research. Using these methodologies, largescale postmarketing surveillance studies similar to the type described in the accompanying articles would constitute an important way of confirming and identifying the determinants of drug safety and effectiveness in large, diverse patient populations.

Anesthesia↗
PubMed1993

Oral transmucosal fentanyl citrate (OTFC) for the treatment of postoperative pain.

Oral transmucosal fentanyl citrate (OTFC) has been used in a variety of clinical situations. This study was designed to determine if OTFC could provide analgesia to patients with acute pain after major surgery. Following written informed consent, 38 ASA Physical Status I-III patients undergoing either a total hip replacement or total knee arthroplasty were studied prospectively. The patients were randomly allocated to receive either OTFC (7-10 micrograms/kg) or a placebo identical in appearance to an OTFC unit. General anesthesia was administered for surgery, and patient-controlled analgesia (PCA) with morphine was initiated in all patients. The PCA interval dose was adjusted to provide adequate analgesia as determined by the patient and physician; the PCA lock-out time was not changed. On the morning after surgery, the most recent 12 h of PCA data (milligrams per hour of morphine and PCA attempts per hour) were recorded. OTFC or placebo units were administered at times 0, 4, and 8 h during a 12-h study, resulting in three identical units being completely consumed. PCA data, as well as incidence and severity of any adverse side effects, were recorded during the study and for the next 12 h. Treatment groups were compared for similarity, and study variables were analyzed. Twenty-eight patients completed the study, 13 in the control group and 15 in the OTFC group. There were no significant differences between the study groups as to patients' age, gender, ASA classification, or surgical procedure. In addition, there were no differences between the groups in the number of PCA attempts or delivered dose of morphine during the prestudy or poststudy periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
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

Novel delivery systems: oral transmucosal and intranasal transmucosal.

During the past 2 decades, anesthesiologists have been provided with a number of new, potent opioid analgesics and sedative/hypnotics, as well as an increased understanding of the pharmacokinetic and pharmacodynamic principles that govern their action and disposition. These developments have suggested that the skin and the buccal and nasal mucous membranes may have use as alternate routes of analgesic and anesthetic drug delivery. A novel transmucosal delivery system for fentanyl has recently been developed by incorporating the drug into a dissolvable matrix on a stick called an "oralete." Oral transmucosal fentanyl citrate has been evaluated as a premedication in the pediatric population and as an analgesicfor acute postoperative and emergency room pain, procedural pain, and breakthrough cancer pain by using fentanyl. Increases in plasma fentanyl and onset of clinical effect are rapid (20-40 min) with this formulation. A potential advantage is the apparent ease of titration to a sedative or analgesic end point. This system may improve premedication, acute postoperative analgesia, and chronic pain therapy in various clinical settings. Delivery of opioids through the nasal mucosa also has been recently investigated. In one study, sufentanil was administered (1.5, 3.0, or 4.5 mu/kg) to 80 children ranging in age from 6 mo to 7yr. Easy separation from parents was achieved in 86% of the children 10 min following administration of the premedication. Unfortunately, 61% of the children cried after drug administration, and side effects included reduced ventilatory compliance (chest-wall rigidity) with higher doses (3.0 and 4.5 microg/kg). Nevertheless, nasal transmucosal drug delivery may have value, especially in frightened or uncooperative children.

Administration, Intranasal↗
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↗