Gastric acidity and glycopyrrolate premedication.
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The pH and volume of gastric contents were examined in 60 patients undergoing elective Caesarean Section under thiopentone, nitrous oxide-oxygen, succinylcholine anaesthesia. All patients received Gelusil 30 ml per os preoperatively, while 20 were given atropine 7 microgram X kg-1 and another 20 glycopyrrolate 4 microgram X kg-1 intramuscularly along with Gelusil. Following tracheal intubation, gastric fluid was sampled through an orally placed 18 French Salem Sump tube. After Gelusil alone, the mean gastric fluid pH was 4.54 +/- 2.45 (SD) while it was significantly higher following the combined use of antacid and atropine (6.78 +/- 1.20) or antacid and glycopyrrolate (6.42 +/- 1.72), (P less than 0.01). Differences in gastric fluid volume between the groups were insignificant. All three regimens produced a gastric pH greater than 2.5 when given less than 75 minutes before sampling. When the premedication to sampling interval exceeded 75 minutes the addition of atropine or glycopyrrolate decreased the incidence of gastric pH less than 2.5 from 47 per cent in patients given Gelusil alone to 6 per cent and 14 per cent, respectively. In comparison to Gelusil alone, this difference was significant with atropine (P less than 0.05) but not with glycopyrrolate. Atropine and glycopyrrolate respectively produced 6 per cent and 7 per cent incidences of pH lower than 2.5 combined with gastric volume greater than 25 ml, which were significantly lower than was observed with Gelusil alone (P less than 0.05). This study demonstrates that the addition of atropine or glycopyrrolate to Gelusil premedication provides additional protection against the consequences of aspiration, especially when the premedication to anaesthetic induction period is prolonged.
BACKGROUND: Nausea and vomiting are the most frequent problems after minor ambulatory surgical procedures. The agents used to induce and maintain anesthesia may modify the incidence of emesis. When neuromuscular blockade is antagonized with anticholinesterases, atropine or glycopyrrolate is used commonly to prevent bradycardia and excessive oral secretions. This study was designed to evaluate the effect of atropine and glycopyrrolate on postoperative vomiting in children. METHODS: Ninety-three patients undergoing tonsillectomy with or without adenoidectomy were studied. After inhalation induction of anesthesia with nitrous oxide, oxygen, and halothane, anesthesia was maintained with a nitrous oxide-oxygen mixture, halothane, morphine, and atracurium. Patients were randomized to receive, in a double-blinded manner, either 15 microg/kg atropine or 10 microg/kg glycopyrrolate with 60 microg/kg neostigmine to reverse neuromuscular blockade. Patient recovery, the incidence of postoperative emesis, antiemetic therapy, and the duration of postoperative hospital stay were assessed. RESULTS: There were no significant differences in age, gender, weight, or discharge time from the postanesthesia care unit or the hospital between the groups. Twenty-four hours after operation, the incidence of vomiting in the atropine group (56%) was significantly less than in the glycopyrrolate group (81%; P<0.05). There was no significant difference between the atropine and glycopyrrolate groups in the number of patients who required antiemetics or additional analgesics. CONCLUSIONS: In children undergoing tonsillectomy with or without adenoidectomy, reversal of neuromuscular blockade with atropine and neostigmine is associated with a lesser incidence of postoperative emesis compared with glycopyrrolate and neostigmine.
The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.
Atropine is routinely used as part of the premedication regimen for fibreoptic bronchoscopy. This study was performed, firstly, to evaluate the effect of anticholinergic agents on the ease of bronchoscopy, haemodynamic parameters and patient comfort during the procedure; and secondly, to compare atropine with glycopyrrolate, a newer acetylcholine antagonist which is claimed to cause less tachycardia and sedation, whilst suppressing salivation more effectively. One hundred and ninety consecutive patients were randomly allocated to three treatment groups: diazepam 5 mg; diazepam 5 mg + atropine 600 micrograms; and diazepam 5 mg + glycopyrrolate 300 micrograms. Diazepam was given orally one hour before bronchoscopy, and glycopyrrolate/atropine intramuscularly 30 min before bronchoscopy. All patients received thalamonal intravenously, lignocaine gel into one nostril, and lignocaine by transtracheal injection just prior to the procedure. The incidence of bronchoscopy related haemodynamic problems was similar in all three groups. Troublesome coughing, as observed by the operator, was less frequent with glycopyrrolate (control 51%, atropine 42%, glycopyrrolate 30%), as was patient movement (40%, 32%, 19%, respectively). Uncomfortable dryness of the mouth was most common with glycopyrrolate (37%, 32%, 66%, respectively), but overall assessment of discomfort, and the number of patients who would agree to a repeat bronchoscopy (73%, 76%, 70%, respectively) were very similar in all three groups. In conclusion, the differences between the three groups were slight. Glycopyrrolate made the bronchoscopy slightly easier for the operator because of significantly improved cough and movement suppression, though atropine was marginally preferable in terms of patient comfort.
BACKGROUND: Because of its pain-attenuating and sedative properties oral ketamine has been used as premedication in children and adults. We wanted to compare in children scheduled for adenoidectomy safety and efficacy of oral ketamine with a premedication that causes similar preoperative sedation and relief of pain at the venepuncture site. We also evaluated the effect of i.v. glycopyrrolate added to these combinations. METHODS: One hundred children between 10 and 15 kg of body weight scheduled for day-case adenoidectomy were randomly assigned to one of four groups: groups DG and DS received diclofenac 12.5 mg and diazepam 0.5 mg/kg rectally, EMLA cream at the venepuncture site, and placebo orally; groups KG and KS received ketamine 6.0 mg/kg orally, placebo cream at the puncture site, and placebo rectally; additionally, groups DG and KG received glycopyrrolate 5 microg/kg, and groups DS and KS received placebo intravenously. We recorded perioperatively scores (open scale 1-9) for stridor, sedation, bleeding, nausea, pain, heart rate, the need for analgesics and registered psychotomimesis and well-being at home. RESULTS: The children of the K-groups became more tearful during separation from their parents (P=0.0072). No other differences were found between the ketamine and diazepam/diclofenac groups before and after premedication until induction of anaesthesia. Oral ketamine produced unpleasant psychotomimesis in four out of 59 children. During the first 10 min postoperatively, the score for stridor was significantly higher in group KS than in the D-groups; stridor scores > or = 6 were seen in one child of the D-groups (DS) and in six children of the K-groups (n.s.), of whom three developed laryngospasm (one reintubation). Glycopyrrolate diminished salivation in all groups, but had no effect on stridor scores. Additionally, glycopyrrolate delayed the onset of eating at home. CONCLUSION: Premedication with racemic oral ketamine 6 mg/kg does not seem to be suitable for upper airway procedures. Addition of i.v. glycopyrrolate before the induction of anaesthesia significantly reduced the scores for salivation.
The effects of premedication on gastric juice volume and pH were evaluated in five groups of 206 pediatric patients undergoing elective surgical procedures: Group 1 (Control) received no premedication; Group 2 was given morphine sulfate and pentobarbital as premedicants. The other groups received, in addition to morphine and pentobarbital, atropine (Group 3), scopolamine (Group 4), or glycopyrrolate (Group 5). After endotracheal intubation, gastric aspirates were examined for volume, pH and color. Neither premedication with morphine and pentobarbital nor addition of atropine or scopolamine to the premedication significantly altered volume. In patients treated with glycopyrrolate, volume was reduced to less than a third of that of patients in Group 1 (P less than 0.001), and the percentage of pH's higher than 2.5 was significantly greater than in other groups. The incidences of unobtainable samples and samples with pH's higher than 2.5 were greatest with atropine (32.0 per cent, P less than 0.05) and glycopyrrolate (58.1 per cent, P less than 0.01). In 60 per cent of the bile-stained specimens, pH's were below 2.5. It is concluded that because of its selective inhibitory effect on gastric acid secretions, glycopyrrolate appears superior to other anticholinergic drugs. The reduction of gastric juice volume and acidity produced by glycopyrrolate would have important clinical implications in case of accidental aspiration. It is also concluded that bile staining of gastric contents is not a reliable indicator of gastric juice pH.
OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.
1. In this study, the analysis of spontaneous baroreflex sensitivity (BRS) was applied to the dynamic assessment of cardiac anticholinergic drug effect in healthy male volunteers. 2. The anticholinergic effects of single intravenous (i.v.) injections of atropine (10 microg kg(-1)), glycopyrrolate (5 microg kg(-1)) and scopolamine (5 microg kg(-1)), as well as a 2-h infusion of glycopyrrolate (5 microg kg(-1) h(-1)) were investigated. Baroreflex sensitivity, a validated measure of cardiac parasympathetic reflex regulation, was repeatedly measured from 5-min recordings of electrocardiogram (ECG) and continuous blood pressure by using the sequence technique, a method based on detection of spontaneous fluctuations in blood pressure and heart rate. 3. Single injections of atropine, glycopyrrolate and scopolamine decreased the mean BRS by 71 +/- 32, 68 +/- 23 and 27 +/- 45%, respectively, whereas the slow glycopyrrolate infusion gradually decreased BRS (up to 83 +/- 11% reduction) and increased both systolic (SAP) and diastolic arterial pressures (DAP) (on an average, by 9 mmHg). 4. During the withdrawal of the parasympathetic blockade (indicated by increasing BRS), the proportion of baroreflex sequences in the recordings increased transiently from 10 up to 20-25%, probably reflecting the restoration of the baroreflex integrity and the baroreflex-induced attempt to counteract the blood pressure increase. 5. The sequence method to study BRS seems to be feasible in the assessment of cardiac anticholinergic drug effects, and it also provides good time resolution for the dynamic measurements.
OBJECTIVE: Large bolus-dose remifentanil may be advantageous for use during induction of anesthesia because of its short duration of effect. Currently, there are little data on the use of large bolus-dose remifentanil because of reports of severe bradycardia and hypotension. The purpose of this study is to compare the hemodynamic effects of bolus remifentanil versus fentanyl with glycopyrrolate for induction of anesthesia in patients with heart disease. DESIGN: A randomized, double-blinded study. SETTING: A tertiary-care academic medical center. PARTICIPANTS: One hundred patients for coronary artery bypass or valvular surgery. INTERVENTION: Subjects received either (1) remifentanil, 5 microg/kg, with glycopyrrolate, 0.2 mg, or (2) fentanyl, 20 microg/kg, with 0.2 mg of glycopyrrolate, and both groups also received midazolam, 70 microg/kg, for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, systemic vascular resistance, and cardiac output were similar between the 2 groups during induction of anesthesia and tracheal intubation. The incidence of adverse events such as bradycardia (remifentanil 10%, fentanyl 10%), hypotension (remifentanil 16%, fentanyl 10%), and ischemia (remifentanil 0%, fentanyl 2%) were also similar. A greater percentage of patients in the remifentanil group lost consciousness within 1 minute of opioid administration (86% v 66%, p = 0.034). CONCLUSION: Remifentanil with glycopyrrolate is associated with rapid and predictable clinical anesthetic effect, cardiac stability, and the ability to blunt the hemodynamic responses to tracheal intubation. Bolus remifentanil may be a feasible alternative to bolus fentanyl for induction of anesthesia in patients with heart disease because of its short duration of action and its ability to blunt the hemodynamic responses to tracheal intubation.