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Effects of clonidine premedication on the pressor response to alpha-adrenergic agonists.

It has been suggested that postjunctional alpha 1-adrenoceptor mediated vasoconstriction is enhanced by clonidine. We have examined in humans if the pressor responses to noradrenaline and phenylephrine are enhanced by clonidine premedication. Seventy-seven patients were allocated randomly to either clonidine (n = 38) or control (n = 39) groups. Patients in the clonidine group received approximately 5 micrograms kg-1 with famotidine 20 mg, while the control group received famotidine 20 mg alone orally, 90 min before induction of general anaesthesia with thiamylal. In all patients the lungs were ventilated mechanically via tracheal tubes and anaesthesia maintained with 1% end-tidal enflurane and 67% nitrous oxide in oxygen. When a stable haemodynamic state was obtained, either noradrenaline 0.5 microgram kg-1 (n = 40) or phenylephrine 2 micrograms kg-1 (n = 37) was administered randomly i.v. as a bolus, while arterial pressure and heart rate were measured noninvasively at 1-min intervals for 10 min. Although noradrenaline caused significantly greater increases in mean arterial pressure (MAP) in the clonidine group (from 2 to 4 min after i.v. injection) compared with the control group, there were no significant differences in the mean maximal increment in MAP or area under the MAP curve between the two groups. However, i.v. phenylephrine produced a significantly greater increase in MAP from 2 to 7 min (P < 0.05), and greater mean maximal increase in MAP from the baseline value (21 (9) vs 14 (7) mm Hg; P < 0.05) in the clonidine than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

I.m. midazolam as premedication produces a concentration-dependent decrease in core temperature in male volunteers.

We tested the hypothesis that premedication with i.m. midazolam decreases core temperature dose-dependently. We studied six male volunteers, in random order, on 3 days: (1) no midazolam administration (control day), (2) midazolam 0.025 mg kg-1 i.m., (3) midazolam 0.075 mg kg-1 i.m. On the first day, subjects were maintained alert during a 30-min control period. On the second and third days, midazolam 0.025 or 0.075 mg kg-1 was administered i.m. Core temperatures were measured at the right tympanic membrane. Four adhesive skin surface probes were fixed on the chest, upper right arm, lateral calf and thigh. Finger tip perfusion was evaluated using forearm minus fingertip and calf minus toe, skin surface temperature gradients. Thirty minutes after midazolam i.m., the level of sedation in the volunteers was assessed. Peripheral venous blood was obtained immediately after the assessment of the level of sedation. Tympanic membrane temperatures after administration of midazolam 0.075 mg kg-1 i.m. were significantly lower than those on the control and midazolam 0.025 mg kg-1 i.m. days at 20 and 30 min. The decreases in tympanic membrane temperatures at 30 min after midazolam i.m. became larger as the volunteers were more deeply sedated. i.m. midazolam produced a concentration-dependent decrease in tympanic membrane temperature at 30 min after midazolam 0.025 and 0.075 mg kg-1 i.m. We conclude that midazolam impaired tonic thermoregulatory vasoconstriction, allowing core-to-peripheral heat redistribution in a dose-dependent manner after i.m. administration.

Adult↗

Neuropeptide Y response to tracheal intubation in anaesthetized children: effects of clonidine vs midazolam as premedication.

We have determined if tracheal intubation causes an increase in neuropeptide Y (NPY), a marker of major adrenergic activation, and investigated if rectal premedication with clonidine 2.5 micrograms kg-1 might be capable of attenuating the stress response to tracheal intubation compared with midazolam 300 micrograms kg-1, in 20 paediatric patients (1-9 yr). Prospective randomization was performed in a double-blind manner. After induction of anaesthesia with 1% isoflurane, tracheal intubation was performed, and norepinephrine, NPY concentrations and haemodynamic variables were recorded. Tracheal intubation did not increase NPY plasma concentrations, despite transient increases in norepinephrine concentrations, heart rate and arterial pressure. There was no significant difference between the two groups. We conclude that the adrenergic stress reaction in response to tracheal intubation in children was short-lived and of limited magnitude, as indicated by the lack of NPY release.

Adrenergic alpha-Agonists↗

Patient-maintained propofol sedation as premedication in day-case surgery: assessment of a target-controlled system.

We have assessed the efficacy and safety of a system which allowed 20 patients undergoing day-case anaesthesia to operate a target-controlled infusion of propofol to provide anxiolytic premedication. A target-controlled infusion of propofol was started with a target blood concentration of 1 microgram ml-1, and the patient was allowed to increase the target by 0.2 microgram ml-1 by operating a control button. There was a lockout time of 2 min and a maximum target concentration of 3 micrograms ml-1. There were significant reductions in anxiety scores from presedation baseline values and those measured at 15 min after the start of sedation. Values remained low until induction of anaesthesia. Median blood target concentration of propofol varied from 1.0 to 1.2 micrograms ml-1 and mean propofol consumption was 50.3 (SD 17.6) micrograms kg-1 min-1. No patient became oversedated and all remained cardiovascularly stable. Two individuals required low-dose supplementary oxygen for mild arterial oxygen desaturation but there were no instances of airway obstruction. Patient satisfaction with the system was high.

Adolescent↗

The effects of premedication on inhaled induction of anesthesia with sevoflurane.

UNLABELLED: The effects of premedication with midazolam (M), fentanyl (F), or both (B) on induction of anesthesia via a mask with sevoflurane (S) were assessed in 24 healthy volunteers who participated on three occasions, receiving either intravenous (IV) F (2.4 microg/kg), M (36 microg/kg), or B (0.6 microg/kg F, 9 microg/kg M) 5 min before three vital capacity breaths of 8% S, 66% N2O, and O2. At loss of lid-lash reflex (LLR), ventilation was manually assisted until a randomly assigned time of administration was attained, at which time laryngoscopy and tracheal intubation were attempted. The effective times for 50% of subjects (ET50) to loss of LLR were 64 s for M and B and 54 s for F (P < 0.05). The ET50 to acceptable intubating conditions were 4.3, 3.1 and 2.5 min for F, M, and B, respectively. F resulted in more airway management difficulties than M or B. Heart rate was slightly increased before intubation in M. Heart rate increases after intubation were least in F, intermediate in B, and greatest in M. The time to achieve good intubating and airway conditions up to intubation was lowest with M or B. Anesthetic adjuvants did not improve the time to achieve loss of consciousness with anesthetic induction via the face mask with sevoflurane, but they significantly decreased the time to acceptable tracheal intubating conditions. IMPLICATIONS: Adults can be anesthetized with very few side effects by breathing themselves to sleep with sevoflurane. Giving patients small doses of sedatives intravenously before they inhale an anesthetic can improve the speed and quality of the process of falling asleep.

Administration, Inhalation↗

The effect of clonidine or midazolam premedication on perioperative responses during ketamine anesthesia.

UNLABELLED: The use of ketamine as a sole anesthetic induces marked central sympathetic stimulation, causing increased heart rate, blood pressure (BP), and oxygen consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to attenuate these potentially harmful ketamine-induced responses. This double-blind, randomized, placebo-controlled study was designed to compare the perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in 30 ASA physical status I patients. The patients received ketamine, mivacurium, and fentanyl for the induction of anesthesia. Anesthesia was maintained using a ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP decreased significantly after the administration clonidine and midazolam compared with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were no significant differences in BP and VO2, although they stayed at lower level in the clonidine group during the whole postoperative period. Clonidine decreased pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our results indicate that a midazolam-ketamine combination may induce potentially harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on ketamine-anesthetized patients may be beneficial, as perioperative VO2 was decreased. IMPLICATIONS: Ketamine causes sympathetic stimulation with an ensuing increase in oxygen consumption. Anticipating that clonidine might attenuate this response, we measured oxygen consumption in patients undergoing surgery during ketamine anesthesia. Patients treated with a clonidine-ketamine combination had lower intra- and postoperative oxygen consumption than those treated with a midazolam-ketamine combination.

Adjuvants, Anesthesia↗

Review of current research on midazolam and diazepam for endoscopic premedication.

This article reviews the current and past research on the use of midazolam and diazepam as endoscopic premedication. The pharmacology and mechanisms of action, use of the medications for endoscopic procedures, dosing schedules, and monitoring are addressed. Several research studies are cited that have examined and compared the two medications during endoscopy, as well as in related medical fields.

Diazepam↗

A twelve-year profile of students' SAT scores, GPAs, and MCAT scores from a small university's premedical program.

PURPOSE: To determine whether significant correlations existed among quantitative and qualitative predictors of students' academic success and quantitative outcomes of such success over a 12-year period in a small university's premedical program. METHOD: A database was assembled from information on the 199 graduates who earned BS degrees in biology from Barry University's School of Natural and Health Sciences from 1980 through 1991. The quantitative variables were year of BS degree, total score on the Scholastic Aptitude Test (SAT), various measures of undergraduate grade-point averages (GPAs), and total score on the Medical College Admission Test (MCAT); and the qualitative variables were minority (54% of the students) or majority status and transfer (about one-third of the students) or nontransfer status. The statistical methods were multiple analysis of variance and stepwise multiple regression. RESULTS: Statistically significant positive correlations were found among SAT total scores, final GPAs, biology GPAs versus nonbiology GPAs, and MCAT total scores. These correlations held for transfer versus nontransfer students and for minority versus majority students. Over the 12-year period there were significant fluctuations in mean MCAT scores. CONCLUSION: The students' SAT scores and GPAs proved to be statistically reliable predictors of MCAT scores, but the minority or majority status and the transfer or nontransfer status of the students were statistically insignificant.

Education, Premedical↗

Premedical enrichment program at East Carolina University School of Medicine.

The Summer Program for Future Doctors, which started in 1978 at East Carolina University School of Medicine, prepares underrepresented-minority (URM), disadvantaged, and nontraditional students for admission to medical school. The annual eight-week program, sponsored by the school's Academic Support and Counseling Center and funded by the school, is a two-pronged program targeting both premedical and pre-matriculating students. The program has 24 openings per year, with priority accorded to students matriculating at the medical school the following fall. The program covers learning strategies, test-taking skills, reading and comprehension tests, MCAT preparation, contemporary issues in the medical environment, scientific writing, communication skills, and medical school applications. Students who have demonstrated strong performances and consistent improvement in the summer program are likely to gain admission to medical school and perform satisfactorily, especially in their first year. Data collected from 1994-1997 indicate that of the 69 participants, 51 (74%) had applied to medical school, and 24 (47%) of them had been admitted, with 15 of these (63%) being URMs. In these four years of the program, there were twice as many women as men among the 69 participants, of which 60% were African Americans, 20% whites, 13% Asian Americans/Pacific Islanders, 3% Native Americans, and 2% Hispanics. Although most of these participants pursued medical education, 12 chose other health professions; 13 students were in or had completed graduate school in basic science programs; and seven had not yet completed their under graduate degrees, although most planned to apply to medical school within the next few years.

Education, Premedical↗

Premedical and predental enrichment program for minority students, 1969-1996, at Meharry Medical College.

From 1969 through 1996, Meharry Medical College offered the Biomedical Sciences Program, an eight-week summer premedical and predental enrichment program designed to increase the enrollment of minority students in health professions schools. The program focused on preparing undergraduates to pursue health professions careers by providing specially designed courses in biology, chemistry, mathematics, and scientific communications, as well as interactions with clinical faculty. The curriculum emphasized academic preparation, including structured course work in the classroom, assigned homework every night, and scheduled activities with clinicians. (The program merged with two other outreach programs in 1996 and is now part of the Health Careers Opportunity Pre-Baccalaureate Program.) From 1969 to 1996, 1,015 students participated in the program, and over the years 43% of them responded to tracking surveys. Of these 445 respondents, 70% (310) applied to professional schools, of whom 83% (257) applied to medical, 15% (46) to dental, and 2% (10) to graduate schools. Of the 257 who applied to medical schools, 70% (198) were admitted and all of them graduated. Of the 46 who applied to dental schools, all were admitted and graduated; and of the ten who applied to graduate schools, all were accepted and received PhD degrees in the biomedical sciences. Of particular note, 67% (172) of the applicants who were admitted to professional schools matriculated at Meharry Medical College. These data suggest that the Biomedical Sciences Program used effective strategies that increased the number of underrepresented-minority students entering health professions careers.

Education, Predental↗

International study in premedical education.

This study surveyed medical school admission deans about the desirability of international study. Most agreed that an international study program in the premedical years was beneficial, but most were neutral concerning science courses taken in international programs.

Attitude of Health Personnel↗

Randomized study of premedication for esophagogastroduodenoscopy in children and adolescents.

In order to compare three premedication regimens, 58 children and adolescents were randomized to three groups: Group I, meperidine intramuscular; Group II, atropine intramuscular and diazepam intravenous; and Group III, meperidine, promethazine, and chlorpromazine intramuscular. Almost all patients required supplemental intravenous diazepam or meperidine to obtain adequate sedation. An endoscopist without knowledge of the medication group scored each patient for adequacy of sedation. Sedation was more effective in Group III than in Groups I and II (p less than 0.005); however, Group III patients were less arousable at completion of the procedure (p less than 0.0005) and had a greater duration of sedation (220 min compared with 56 and 88 min for Groups I and II, respectively, p less than 0.001). Complications were minor and not associated with any specific treatment. The evidence from this study supports the following conclusions: (a) adequate sedation for esophagogastroduodenoscopy in pediatric patients requires sedation with more than one of the drugs used in this study; and (b) the regimen meperidine, promethazine, and chlorpromazine, with diazepam supplement, was superior in providing sedation, but patients required a longer period of recovery than did patients sedated with one of the other regimens.

Adolescent↗

Review article: premedication and intravenous sedation for upper gastrointestinal endoscopy.

Upper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests that, in the United Kingdom and United States, most patients and endoscopists prefer that some form of premedication is given. Intravenous diazepam or midazolam are used by the majority of endoscopists. In the UK, the ratio of diazepam to midazolam users is approximately 2:1, while in the USA more endoscopists are now using midazolam. Midazolam is approximately twice as potent as diazepam but, when allowance is made for this, there is probably little or no difference in the propensity of the two drugs to produce respiratory depression. The antegrade amnesic effect of midazolam is significantly superior to that of diazepam. A benzodiazepine/narcotic combination can achieve a smoother and more rapid induction with less gagging and choking, but the incidence of adverse outcomes--particularly respiratory depression--is increased significantly. Over 50% of the deaths that are associated with upper gastrointestinal endoscopy are due to cardiopulmonary problems. Hypoxia is very common if measured using non-invasive monitoring equipment, such as a pulse oximeter. Methods of preventing oxygen desaturation and thus, by inference, most cardiac arrhythmias associated with endoscopy are discussed, as is the role of flumazenil, the new benzodiazepine antagonist.

Endoscopy, Gastrointestinal↗

An investigation of premedication with morphine given by the buccal or intramuscular route.

1. Premedication with 30 mg buccal morphine or 10 mg intramuscular morphine was evaluated in 40 healthy women undergoing major gynaecological surgery. 2. Buccal administration of morphine produced lower plasma morphine concentrations than intramuscular injection of morphine (P less than 0.01). 3. The mean systemic availability of the buccal tablet, during the first 5 h after administration, was approximately 3% relative to that of the intramuscular preparation. 4. Poor absorption of buccal morphine resulted in inadequate sedation prior to surgery and poor post-operative analgesia. 5. Patients experienced difficulty with the buccal formulation of morphine; tablet bitterness and failure to dissolve were particular problems.

Administration, Buccal↗

Combined premedical-medical programmes: programme structure and student outcomes at four universities.

Many American universities now support combined premedical-medical programmes which shorten and integrate the education of doctors. This paper reviews combined baccalaureate-MD programmes at four institutions: Boston University, the City College of New York, The University of Michigan-Ann Arbor, and the University of Missouri-Kansas City. In comparison to most US medical schools, the combined programmes have admitted and educated larger portions of women students. In addition, some have had large proportions of graduates choosing primary-care careers.

Boston↗

Flunitrazepam versus placebo premedication for minor surgery.

The clinical effects of oral flunitrazepam (2 mg on the night before operation followed by 2 mg on the morning of operation) and placebo as premedicants were tested in a double-blind study in 81 gynaecological patients. The separate or total concentrations of flunitrazepam and its demethylated metabolite in plasma (measured by gas chromatography) were correlated with the clinical effects of flunitrapam premedication, assessed both sugjectively and objectively. In most parameters tested (sleep on the night before operation, sedation, apprehension, headache, pulse rate), there was a positive, significant difference between the flunitrazepam group (n = 44) and the placebo group (n = 37). No significant difference was found between the two groups in emetic effect, excitement, systolic blood pressure increase, and vene-puncture, but the patients receiving flunitrazepam felt significantly more dizziness. The temperature of the left forefinger before, during and after the anaesthesia did not vary significantly between the two groups. There was no correlation between the plasma concentration of flunitrazepam and its demethylated metabolite (separate or total concentrations) and any of the parameters tested before induction of anaesthesia. Flunitrazepam is a new oral premedicant with prominent sedative and anxiolytic actions. When the drug is given as a sedative on the night before operation, followed by a second dose on the morning of operation, the beneficial effects last for at least 8 hours after the second dose.

Adult↗

Reduction of the risk of acid pulmonary aspiration in anaesthetized patients after cimetidine premedication.

Forty-two patients undergoing elective general surgery received either placebo, cimetidine 300 mg, or cimetidine 600 mg orally 1.5-2 h before anaesthesia in a double-blind, randomized study. Another 13 subjects received no oral premedication and served as a control group. When compared to placebo or control patients, both doses of cimetidine significantly (P less than 0.01) decreased the acidity and volume of gastric contents. None of the subjects given cimetidine were in the risk range of acid pulmonary aspiration (pH under 2.5 plus volume over 25 ml), whereas 46% of the control patients and 40% of the patients given placebo (P less than 0.005 vs cimetidine in both groups) were in the risk range.

Administration, Oral↗

Gastric contents and pH after oral premedication.

Forty women, aged 26-40 years, were investigated with regard to gastric contents and pH before general anaesthesia. The patients were divided into two groups (20 in each). Group 100 received 0.3 mg kg-1 diazepam orally with 100 ml of water 2 h before surgery. Group 50 received 0.3 mg kg-1 diazepam with 50 ml of water 2 h before surgery. The amount of gastric content was significantly greater in Group 100 than in Group 50 (P less than 0.05). There was no statistical difference in pH values between the groups. The number of patients with both gastric pH less than 2.5 and gastric volume greater than 25 ml was significantly higher in Group 100 compared to Group 50 (P less than 0.05). We cannot recommend the use of oral premedication using these amounts of water, considering the increased risk of aspiration of gastric contents.

Administration, Oral↗