Effects of anticholinergics on postoperative vomiting, recovery, and hospital stay in children undergoing tonsillectomy with or without adenoidectomy.
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. (+info)
Neostigmine with glycopyrrolate does not increase the incidence or severity of postoperative nausea and vomiting in outpatients undergoing gynaecological laparoscopy.
We studied 100 healthy women undergoing outpatient gynaecological laparoscopy in a randomized, double-blind and placebo-controlled study to evaluate the effect of neostigmine on postoperative nausea and vomiting (PONV). After induction of anaesthesia with propofol, anaesthesia was maintained with sevoflurane and 66% nitrous oxide in oxygen. Mivacurium was used for neuromuscular block. At the end of anaesthesia, neostigmine 2.0 mg and glycopyrrolate 0.4 mg, or saline, was given i.v. The incidence of PONV was evaluated in the postanaesthesia care unit, on the ward and at home. The severity of nausea and vomiting, worst pain, antiemetic and analgesic use, times to urinary voiding and home readiness were recorded. During the first 24 h after operation, 44% of patients in the neostigmine group and 43% in the saline group did not have PONV. We conclude that neostigmine with glycopyrrolate did not increase the occurrence of PONV in this patient group. (+info)
Dose effect and benefits of glycopyrrolate in the treatment of bradycardia in anesthetized dogs.
This study evaluated the effectiveness of glycopyrrolate (0.005 or 0.01 mg/kg body weight (BW)) in anesthetized dogs (n = 40) for reversal of bradycardia (< 65 beats/min). Following random intravenous (i.v.) treatment, heart rate was determined at 5 min and, if it was < or = 70 beats/min, the lower dose was repeated. A 2-way analysis of variance considered dose and animal size (< or = 10 kg, > 10 kg) effects (P < 0.05). Glycopyrrolate produced a significant increase in heart rate and infrequent tachycardia (< or = 150 beats/min), which was not dose-related. The size of the dog produced a significant effect on baseline heart rate (higher in small), rate following the first dose (lower in small), and requirement for retreatment (47% in small, 13% in large). In a separate group of anesthetized dogs (n = 20), the blood pressure effect of glycopyrrolate (0.01 mg/kg BW, i.v.) treatment of bradycardia (65-85 beats/min, weight-adjusted) was studied. A significant increase in systolic, diastolic, and mean blood pressure was produced. In conclusion, the effective dose of glycopyrrolate treatment is size-related and produces a beneficial effect on blood pressure. (+info)
Glycopyrrolate reduces nausea during spinal anaesthesia for caesarean section without affecting neonatal outcome.
We have tested the hypotheses that glycopyrrolate, administered immediately before induction of subarachnoid anaesthesia for elective Caesarean section, reduces the incidence and severity of nausea, with no adverse effects on neonatal Apgar scores, in a double-blind, randomized, controlled study. Fifty women received either glycopyrrolate 200 micrograms or saline (placebo) i.v. during fluid preload, before induction of spinal anaesthesia with 2.5 ml of 0.5% isobaric bupivacaine. Patients were questioned directly regarding nausea at 3-min intervals throughout operation and asked to report symptoms as they arose. The severity of nausea was assessed using a verbal scoring system and was treated with increments of i.v. ephedrine and fluids. Patients in the group pretreated with glycopyrrolate reported a reduction in the frequency (P = 0.02) and severity (P = 0.03) of nausea. Glycopyrrolate also reduced the severity of hypotension, as evidenced by reduced ephedrine requirements (P = 0.02). There were no differences in neonatal Apgar scores between groups. (+info)
Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways.
1. In this study we have evaluated the pharmacological profile of the muscarinic antagonist glycopyrrolate in guinea-pig and human airways in comparison with the commonly used antagonist ipratropium bromide. 2. Glycopyrrolate and ipratropium bromide inhibited EFS-induced contraction of guinea-pig trachea and human airways in a concentration-dependent manner. Glycopyrrolate was more potent than ipratropium bromide. 3. The onset of action (time to attainment of 50% of maximum response) of glycopyrrolate was similar to that obtained with ipratropium bromide in both preparations. In guinea-pig trachea, the offset of action (time taken for response to return to 50% recovery after wash out of the test antagonist) for glycopyrrolate (t1/2 [offset]=26.4+/-0.5 min) was less than that obtained with ipratropium bromide (81.2+/-3.7 min). In human airways, however, the duration of action of glycopyrrolate (t1/2 [offset]>96 min) was significantly more prolonged compared to ipratropium bromide (t1/2 [offset]= 59.2+/-17.8 min). 4. In competition studies, glycopyrrolate and ipratropium bromide bind human peripheral lung and human airway smooth muscle (HASM) muscarinic receptors with affinities in the nanomolar range (K1 values 0.5-3.6 nM). Similar to ipratropium bromide, glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide. 5. These results suggest that glycopyrrolate bind human and guinea-pig airway muscarinic receptors with high affinity. Furthermore, we suggest that the slow dissociation profile of glycopyrrolate might be the underlying mechanism by which this drug accomplishes its long duration of action. (+info)
Orthostatic hypotension in aging humans.
We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP. (+info)
Effects of 8 h of isocapnic hypoxia with and without muscarinic blockade on ventilation and heart rate in humans.
This study examined the role of muscarinic parasympathetic mechanisms in generating the progressive increases in ventilation (V(E)) and heart rate previously reported with 8 h exposures to hypoxia. The sensitivities of V(E) (G(p)) and heart rate (G(HR)) to acute variations in hypoxia, and V(E) and heart rate during acute hyperoxia were assessed in 10 subjects before and after two 8 h exposures to isocapnic hypoxia (end-tidal P(O2) = 50 mmHg). The responses were measured during muscarinic blockade with glycopyrrolate (0.015 mg kg(-1)) and without glycopyrrolate, as a control. There were significant increases in G(p) (P < 0.01) and V(E) during hyperoxia (P < 0.01) following hypoxic exposure, but these were unaffected by glycopyrrolate. G(HR) increased significantly by 0.29 +/- 0.08 beats min(-1) %(-1) (mean +/- S.E.M.) following exposure to hypoxia under control conditions, but only non-significantly by 0.10 +/- 0.08 beats min(-1) %(-1) with glycopyrrolate. This difference was significant. Changes in heart rate during hyperoxia were slight and inconclusive. We conclude that muscarinic mechanisms play little role in the progressive ventilatory changes that occur over 8 h of hypoxia, but that they do mediate much of the progressive increase in heart rate. Experimental Physiology (2001) 86.4, 529-538. (+info)
Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.
Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal. (+info)