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Atracurium and its antagonism by neostigmine (plus glycopyrrolate) in patients susceptible to malignant hyperthermia.

Forty patients undergoing diagnostic muscle biopsy as part of investigation for malignant hyperthermia (MH) were given atracurium 0.45 +/- 0.10 mg kg-1 for muscle paralysis. The neuromuscular blockade was antagonized with neostigmine 2.4 +/- 0.4 mg given with glycopyrrolate 0.47 +/- 0.09 mg. Rectal, muscle and skin temperatures and blood lactate concentration and venous Pco2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the regimen of the European MH Group. Fifteen patients were susceptible to MH (MHS), 19 were MH-negative (MHN) and six were MH-equivocal (MHE). No side effects of the drugs were noted. There were no differences between the three groups of patients in any of the measurements.

Adult↗

Evaluation of the combined effects of glycopyrrolate and neostigmine on the lower oesophageal sphincter.

The effects on the lower oesophageal sphincter (LOS) of the simultaneous administration of glycopyrrolate 0.5 mg and neostigmine 2.5 mg, when given to antagonize neuromuscular blockade, were studied in 10 healthy patients undergoing gynaecological surgery. LOS pressure and gastric pressure (GP) were measured for 20 min after the administration of the drug combination and barrier pressure (BrP) was calculated (LOS-GP). There was a significant reduction in BrP which lasted, in some patients, for the duration of the study. These results contrast with those of a similar study looking at the effects of atropine and neostigmine in which the decrease in BrP, although significant, was transient, and in which control values were regained after 5 min.

Drug Evaluation↗

Postanaesthetic arousal time in elderly patients. A double-blind study of glycopyrrolate and atropine.

Postanaesthetic arousal time was studied in elderly patients given either glycopyrrolate 0.01 mg kg-1 or atropine 0.02 mg kg-1 before antagonism of neuromuscular blockade. Forty patients (age greater than or equal to 65 yr) undergoing elective hip replacement were included in a double-blind study. Arousal was scored for 2 h after recovery using a modified scoring system. No difference in arousal time was found between the two groups.

Aged↗

Effect of pre-treatment with intravenous atropine or glycopyrrolate on cardiac arrhythmias during halothane anaesthesia for adenoidectomy in children.

We studied the effect of anticholinergics on the incidence of cardiac arrhythmias during paediatric anaesthesia. ASA I-II children (n = 77) undergoing adenoidectomy were randomly allocated to three groups. Intravenous atropine 0.02 mg kg-1 was given in group A (n = 25), glycopyrrolate 0.004 mg kg-1 in group G (n = 27) and physiological saline in group P (n = 25) 3 min before the induction of anaesthesia. The children breathed spontaneously under halothane anaesthesia with 66% nitrous oxide in oxygen after induction with thiopentone and succinylcholine. Perioperative monitoring of the ECG (Holter recordings) and oxygen saturation was carried out. Ventricular tachycardia occurred in 16.0%, 18.5% and 12.0% of the children in groups A, G and P respectively (ns). The incidence of ventricular arrhythmias (ventricular tachycardia, ventricular bigeminy, ventricular premature beats > 10) was 20.0% in group A, 44.4% in group G and 36.0% in group P (ns). Bradycardia (< 70 beats min-1) was observed in 0.0%, 14.8% and 24.0% of patients in groups A, G and P respectively (A vs P, P < 0.05). The use of anticholinergics did not influence the incidence of ventricular arrhythmias during halothane anaesthesia in children. Bradycardia was more common in the placebo group than in the atropine group.

Adenoidectomy↗

Atropine versus glycopyrrolate. A study of intraocular pressure and pupil size in man.

Following control observations of intraocular pressure and pupil size, in doses suitable for pre-anaesthetic medication, glycopyrrolate (0.004 mg/kg) and atropine (0.01 mg/kg) were given intramuscularly to healthy volunteers in a randomised, cross-over fashion. No significant change in either intraocular pressure or pupil size was noted 45 min after drug administration.

Adult↗

Effect of glycopyrrolate and atropine on thermoregulation after exercise.

The effects of two anticholinergic drugs on heat production (derived from oxygen consumption), sweating and core and skin temperature were compared with saline placebo in five healthy volunteers, before and after exercise. There were no significant differences between the groups in resting and peak heat production after exercise. Sweat evaporation rate increased after exercise in all cases, but there was individual variation in response to the drugs. Sweat evaporation was greater after saline placebo compared with atropine, but not after glycopyrrolate compared with saline placebo or atropine. In the saline placebo group, increased sweat evaporation following exercise was reflected by an initial fall, in skin temperature. Following anticholinergic drugs, skin temperature increased after exercise without an initial decrease. Core temperature increased following exercise, but there were no significant differences between the anticholinergic drugs and saline placebo. Although clinical doses of anticholinergic drugs, when compared with saline placebo, inhibited sweating after exercise, core temperature was not significantly increased. Therefore it is suggested that non-evaporative heat loss compensated for the reduction in sweating due to anticholinergic drugs.

Adult↗

Glycopyrrolate during ketamine/diazepam anaesthesia. A double-blind comparison with atropine.

In a double-blind study, the effects of atropine and glycopyrrolate (dosage ratio 2:1) following i.m. and i.v. administration were compared with respect to salivation, heart rate, and blood pressure before, during and after i.v. infusion anaesthesia with ketamine and diazepam for alloplastic hip or knee surgery in 30 patients above the age of 50 years. Given with the premedicant, the two drugs were equally effective in reducing salivation. A slight increase in heart rate was seen after atropine only (P less than 0.005). Increases in heart rate and blood pressure during induction of anaesthesia were similar in the two groups. A second dose of the test drug was given with neostigmine for reversal of neuromuscular blockade. Again, there were no statistically significant differences with respect to salivation, blood pressure, heart rate, nausea and/or vomiting, unpleasant dreams and arousal time.

Aged↗

Pharmacokinetic implications for the clinical use of atropine, scopolamine and glycopyrrolate.

Several specific and sensitive new methods for determining atropine and its metabolites in biological fluids have increased the possibility to characterise the pharmacokinetic properties of this antimuscarinic agent. Following i.v. injection, atropine disappears very quickly from the circulation, resembling its fast onset of action. Age, but not sex, appears to have a clear effect on its kinetics, explaining at least partly the higher sensitivity of very young and very old patients to this anticholinergic agent. Following i.m. or oral atropine administration, typical anticholinergic effects coincide quite well with the absorption rate of the drug, indicating that the premedication should be given about 1 and 2 h before induction of anaesthesia. A sufficient absorption after rectal administration offers an alternative treatment, especially in children. Differing from its placental transfer, atropine has a delayed and incomplete lumbar cerebrospinal fluid penetration, indicating a fundamental difference between these two biological membranes. Oropharyngeally administered atropine has a very variable absorption, but inhaled or intratracheally given drug has produced interesting new results, e.g. pulmonary atropine administration appears to have clinical significance in special situations, such as cardiac arrest and organophosphate poisoning (military personnel). Depending on the method used, different data on the metabolism and excretion for atropine have been reported and therefore further studies are needed in this respect. The pharmacokinetics of scopolamine and glycopyrrolate and their relation to clinical response are poorly understood.

Aging↗

Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy.

As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study.

Adult↗

Intravenous glycopyrrolate and atropine at induction of anaesthesia: a comparison.

In unpremedicated patients presenting for general anaesthesia for electroconvulsive therapy (ECT), the use of atropine combined with methohexitone as an intravenous induction agent was found to produce a significantly greater increase in heart rate than glycopyrrolate in similar combination. There was no difference in the antisialogogue effect of the two drugs at the doses used, and both drugs provided similar protection against the effects of suxamethonium and ECT on heart rate.

Anesthesia, General↗

Effect of inhaled glycopyrrolate and atropine in asthma. Precipitated by exercise and cold air inhalation.

We compared the effects of inhaled glycopyrrolate (G), 1.3 mg, and atropine (A), 2.6 mg, and placebo on FEV1 and specific conductance (sGaw) before and after exercise in six men with exercise-induced asthma. Subjects exercised with cold air (-2 degrees C) 30 and 120 minutes after each aerosol treatment. Spirometry was performed and sGaw determined before aerosol treatment (baseline) and before and after exercise. Decreased airway tone was noted before exercising with A and G but not with placebo. The decreases in FEV1 and sGaw resulting from exercise were not significantly different among the three treatment groups at either exercise session. Postexercise FEV1 and sGaw were significantly higher after A and G compared to P. Dry mouth, flushing, and resting tachycardia were prominent with group A. Symptoms in G did not differ from those in P. This study suggests that A and G do not prevent bronchoconstriction induced by exercise and cold air but improve postexercise pulmonary function by achieving preexercise bronchodilation. Systemic side effects were minimal with G compared to A.

Adolescent↗

Glycopyrrolate in 99mTc-pertechnetate brain imaging.

Glycopyrrolate, a synthetic anticholinergic agent, was administered parenterally to two groups of patients referred for 99mTc-pertechnetate brain imaging to assess its ability to suppress pertechnetate uptake by the choroid plexus, oral mucosa, and salivary (parotid) glands. Pertechnetate activity was almost completely eliminated from the choroid plexus and mouth and appeared to be moderately reduced in the parotid gland. The drug can be given orally and may prove valuable in pertechnetate brain imaging.

Brain↗

[Atropine versus glycopyrrolate in eye surgery. A comparison of rhythm disorders and heart frequency using Holter-ECG].

Anticholinergics are indicated in ophthalmic surgery to inhibit oculocardiac reflexes (OCR). Although all anticholinergics exert an arrhythmic effect, comparative data on occurrence and severity of arrhythmias are not available. The aim of this investigation was to compare atropine (A) and glycopyrrolate (G) in adults undergoing ophthalmic surgery. One hundred patients (ASA class I and II, age range 20-60 yrs.) were given equipotent doses of either A (10 micrograms.kg-1) or G (5 micrograms.kg-1) in a randomized, double-blind fashion, before induction of anaesthesia. Continuous Holter monitoring was performed. The procedure was divided into the following phases: O (5 min before drug), I (5 min after drug), II (up to induction), III (induction until intubation), IV (intubation until operation), V (operation). Supraventricular, junctional, and ventricular arrhythmias were analyzed. Severe arrhythmia was judged to be greater than 5 events per min, or ventricular beats Lown classes III-V. The beat to beat analog signal was digitalized. The heart rate (HR) and the occurrence rate of OCR (greater than 20% decrease in heart rate, arrhythmias) was calculated by a computerized program. Analysed were: 1. the frequency of OCR, 2. the mean HR for each phase, 3. the frequency of all the various arrhythmias during the whole period, 4. as well as for each phase. The number of patients with severe arrhythmias 5. either for all the time or 6. for the individual phase were registered separately. There were no differences 1. in the frequency of OCR and 2. in mean HR during all phases between A and G.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects on cardiac rhythm of premedication with atropine or glycopyrrolate.

The effect of the premedicants atropine and glycopyrrolate on the cardiac dysrhythmic response to instrumentation and intubation was investigated. No significant increase in cardiac dysrhythmias such as bradycardia, atrial and ventricular extrasystoles was found (P greater than 0,01), but a significant increase in tachycardia occurred during induction (P less than 0,05) and intubation (P less than 0,01).

Adult↗

Anticholinergic premedication in infants: a comparison of atropine and glycopyrrolate on heart rate, demeanor, and facial flushing.

Heart rate, demeanor, and facial flushing following intramuscular injection of atropine or glycopyrrolate were compared in 80 paediatric patients under 1 year of age. No significant differences occurred between the two drugs in the doses used. Neither was there any difference in drug response between those children aged under 2 months and the other patients in the study.

Akathisia, Drug-Induced↗

Use of glycopyrrolate in the parturient: effect on the maternal and fetal heart and uterine activity.

The effects of intravenous glycopyrrolate on maternal and fetal heart rate, heart rate variability, and maternal electromechanical intervals and blood pressure were evaluated in 20 term parturients in labor. Direct continuous fetal heart rate and intrauterine pressure were monitored via an intrauterine catheter. Maternal heart rate and R-pulse-wave intervals were measured and maternal blood pressure was recorded at 5-minute intervals. There were no significant changes in fetal heart rate or fetal heart rate variability. The maternal heart rate increased in all cases and the electromechanical interval decreased with the onset of maternal tachycardia. There were no significant changes in maternal blood pressure. Uterine activity increased in all cases; however, this increase does not appear to be greater than that expected in uterine activity as labor progresses.

Blood Pressure↗