Glycopyrrolate Group Research Articles

Effects of glycopyrrolate premedication on preventing postoperative catheter-related bladder discomfort in patients receiving ureteroscopic removal of ureter stone.

BackgroundGlycopyrrolate given as reversing agents of muscle relaxants has been reported to be effective in reducing postoperative catheter-related bladder discomfort (CRBD). However, it remains unclear whether glycopyrrolate as premedication is also effective. This study aims to investigate the effectiveness of glycopyrrolate as premedication on preventing CRBD in the post-anesthesia care unit (PACU).MethodsEighty-three patients who received elective ureteroscopic removal of ureteral stone were randomly assigned to the control (n = 43) or the glycopyrrolate group (n = 40). The glycopyrrolate group was treated with glycopyrrolate 0.3 mg as premedication while the control group received 0.9% saline 1.5 ml. The incidence and severity of CRBD and pain score using numerical rating scale (NRS) were measured in the PACU.ResultsThe incidence of CRBD (26 of 40 patients vs. 41 of 43 patients, relative risk [RR] = 0.68, 95% Confidence interval [CI] = 0.53–0.86, P = 0.001) and the moderate to severe CRBD incidence (6 of 40 patients vs. 20 of 43 patients, RR = 0.32, 95% CI = 0.14–0.72, P = 0.002) were lower in the glycopyrrolate group than in the control group. Also, postoperative pain NRS score was found to be lower in the glycopyrrolate group (median = 1 [Q1 = 0, Q3 = 2]) compared to the control group (3 [1, 5], median difference = 1.00, 95% CI = 0.00–2.00, P = 0.002).ConclusionsThe use of glycopyrrolate 0.3 mg as premedication in patients receiving ureteroscopic removal of ureteral stone reduced the incidence and severity of CRBD, and decreased postoperative pain in the PACU.

A comparative study of effects of glycopyrrolate and ondansetron on nausea and vomiting in cesarean section under spinal anesthesia.

Background and Aim:Nausea and vomiting causes distress to patients and increases surgical complications. Though various antiemetics are available, their effectiveness and fetal safety profile when used in parturient remains debatable. This randomized, double-blind, comparative study was designed with an aim to compare the antiemetic effects of ondansetron and glycopyrrolate during cesarean section.Methods:Sixty-six parturients (American Society of Anesthesiologist physical status I-II) scheduled for elective cesarean section were randomized to receive intravenous ondansetron 4 mg (Group O, n = 32) or glycopyrrolate 0.2 mg (Group G, n = 31) before spinal anesthesia. Outcome measures studied were emesis, episodes of hypotension and bradycardia and pain, till 10 h postoperative. Statistical software used was Epi Info 7 and Microsoft Excel.Results:There was no significant difference in nausea and vomiting at all the study intervals between the two groups statistically. There was no difference in episodes of hypotension, but episodes of bradycardia were significantly less in glycopyrrolate group (26%) than in ondansetron group (56%) (P = 0.027). There was no difference in additional analgesic requirements. However, the incidence of dry mouth was significantly greater in glycopyrrolate group (21 [68%]) as compared to ondansetron group (5 [16%]) (P = 0.00).Conclusion:Effect of glycopyrrolate on nausea and vomiting during cesarean section are comparable to ondansetron, but with an increased incidence of dry mouth. Glycopyrrolate has no effect on hypotension or additional analgesic requirements, but the incidence of bradycardia is significantly less.

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous-rate infusion in the horse

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2-h constant-rate intravenous infusion (4 μg/kg/h) and evaluate potential PK-PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri-exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8-h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment.

Haemodynamic effects of glycopyrrolate pre-treatment before phenylephrine infusion during spinal anaesthesia for caesarean delivery

BackgroundPhenylephrine given during spinal anaesthesia for caesarean delivery often induces a decrease in heart rate which may decrease cardiac output. Anticholinergic drugs may be given to attenuate this effect but may also cause more labile blood pressure. This study evaluated the effects of glycopyrrolate pre-treatment on non-invasively measured cardiac output and accuracy of blood pressure control. MethodsAt induction of spinal anaesthesia for caesarean delivery, 104 patients randomly received intravenous glycopyrrolate 4μg/kg or saline placebo. Systolic blood pressure, measured at 1-min intervals, was maintained near baseline using closed-loop feedback computer-controlled phenylephrine infusion with crystalloid cohydration. Cardiac output and stroke volume were measured using suprasternal Doppler ultrasonography at baseline and 5-min intervals for 20min. Blood pressure control was assessed using performance error calculations. ResultsEleven patients were excluded. Patients who received glycopyrrolate (n=45) had greater cardiac output over time (P<0.001), greater heart rate over time (P<0.001), similar stroke volume over time (P=0.95), and lower median phenylephrine infusion rate (P=0.006) compared with control (n=48). There was no difference in the incidence of hypotension between groups. Analysis of blood pressure control showed greater positive bias, greater inaccuracy and greater wobble in the glycopyrrolate group (all P<0.05). Neonatal outcome was similar between groups. ConclusionsGlycopyrrolate 4μg/kg given at the start of a phenylephrine infusion increased heart rate and cardiac output but also decreased accuracy of blood pressure control, increased the incidence of hypertension and caused an increased incidence of dry mouth postoperatively compared with control.

Comparison of hemodynamic changes between phenylephrine and combined phenylephrine and glycopyrrolate groups after spinal anesthesia for cesarean delivery.

BackgroundHypotension remains a common clinical problem of spinal anesthesia for cesarean delivery and phenylephrine is used as a vasopressor to address this. However, phenylephrine reduces maternal cardiac output (CO) due to reflex bradycardia. Glycopyrrolate is safe for the fetus, and increases heart rate (HR). Using a noninvasive measure of CO, we compared maternal hemodynamic changes between the phenylephrine only group (group P) and the phenylephrine plus glycopyrrolate group (group PG).MethodsIn this randomized study, 60 women scheduled for elective cesarean delivery were allocated to group P (n = 30) or group PG (n = 30). In both groups, phenylephrine was infused at 50 µg/min. This infusions stopped if systolic blood pressure (SBP) was higher than the baseline value, and phenylephrine 100 µg was injected if SBP was lower than 80% of the baseline value from spinal anesthesia to delivery. In group PG, glycopyrrolate 0.2 mg was injected intravenously after spinal anesthesia. Hemodynamic parameters, such as SBP, heart rate (HR), stroke volume index (SVI), cardiac index (CI) were measured before and until 15 min after spinal anesthesia.ResultsThere were no significant differences in SBP and SVI compared to the baseline value in each group and between the two groups. HR and CI reduced significantly from 8 min to 15 min in group P compared to the baseline value as well as group PG for each time-point. However, HR and CI were maintained in group PG.ConclusionsThe use of glycopyrrolate added to phenylephrine infusion to prevent hypotension by spinal anesthesia for cesarean delivery was effective in maintaining HR and CI.

Glycopyrrolate Does Not Reduce the Incidence of Perioperative Adverse Events in Children with Upper Respiratory Tract Infections

Two recent studies have identified copious secretions as an independent risk factor for perioperative adverse events in children who present for elective surgery in the presence of an upper respiratory tract infection (URI). We designed this study, therefore, to determine whether the administration of the anticholinergic drug, glycopyrrolate, to children with URIs would reduce the incidence of adverse perioperative respiratory events. One hundred thirty children (1 mo to 18 yr of age) who presented for elective surgery with a URI were randomized to receive either 0.01 mg/kg glycopyrrolate or placebo and were followed for the appearance and severity of any perioperative respiratory adverse events. The two groups were similar with respect to demographics, presenting URI symptoms, anesthetic management, and surgical procedure. In the intention-to-treat analysis, there were no statistical differences in the incidence or severity of perioperative respiratory adverse events between the glycopyrrolate and placebo groups (45.2% vs 37.5% respectively, P = NS). Furthermore, there were no differences in outcome between the two groups when children with congestion and secretions were analyzed separately (45.0% vs 37.0%, respectively). However, compared with the placebo group, children in the glycopyrrolate group had significantly shorter discharge times (83.9 min vs 111.4 min, P = 0.024), and significantly less postoperative nausea and vomiting (10.7% vs 33.3%, P = 0.005). These results suggest that glycopyrrolate, administered after induction of anesthesia to children with URIs, does not reduce the incidence of perioperative respiratory adverse events, and thus may not be clinically indicated for routine use in this population.

Optimizing Aerosol Gene Delivery and Expression in the Ovine Lung

We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

Core Temperature Changes according to Premedication

Background: It is well known that body core temperature reduces during general anesthesia. Midazolam premedication for relieving anxiety might also reduce body core temperature by inhibiting tonic thermoregulatory vasoconstriction in elderly patients. Therefore, an effort to maintain temperature must be started before anesthesia. This study was designed to evaluate the effect on body core temperature of midazolam, atropine and glycopyrrolate, which are commonly used for premedication. Methods: Six hundred and eleven patients of ASA physical status 1 or 2, aged 18 to 65, were involved in this study. They were randomly assigned to premedication with: 1) saline control (n = 92); 2) midazolam 0.04 mg/kg (n = 96); 3) midazolam 0.04 mg/kg with glycopyrrolate 0.004 mg/kg (n = 117); 4) midazolam 0.04 mg/kg with atropine 0.01 mg/kg (n = 93); 5) glycopyrrolate 0.004 mg/kg (n = 116); and 6) atropine 0.01 mg/kg (n = 97). All premedication was given intramuscularly about 30 min before operation. Temperatures were measured at the tympanic membrane at the time of premedication and 30 min after premedication. Results: Temperatures increased slightly after injection in the control (0.14 ; mean SD) and this increase was less in the midazolam group (0.07 . The changes of temperature in the midazolam with glycopyrrolate (0.16 . midazolam with atropine (0.19 . ), and in the glycopyrrolate group were no different from that of the control group. However, there was a statistically significant increase in temperature after injection in the atropine group (0.26 ) versus the control group. Compared with the midazolam group, a statistically significant increase in temperature was observed in the midazolam with atropine, the glycopyrrolate, and in the atropine group. Conclusions: From these results, low dose midazolam (0.04 mg/kg), midazolam with glycopyrrolate, and midazolam with atropine for premedication have little affect on temperature. Midazolam with glycopyrrolate premedication is recommended for preserving body core temperature.

The Effects of Glycopyrrolate on Oral Mucous Host Defenses in Healthy Volunteers

We studied the effects of glycopyrrolate on oral mucous host defenses. Single IV doses of glycopyrrolate (4 μg/kg) or placebo were administered to 12 healthy volunteers in a randomized, double-blinded, cross-over study. Salivary flow rates and the concentrations/activities of total protein, amylase, and nonimmunologic (lysozyme, lactoferrin, myeloperoxidase, total salivary peroxidase, and thiocyanate) and immunologic (total immunoglobulin A, immunoglobulin G, and immunoglobulin M) mucous host defense factors were determined for paraffin-stimulated whole saliva before and 1, 3, 6, 12, 24, and 48 h after drug administration. Glycopyrrolate serum concentrations were determined before and 2, 4, 6, 10, 15, and 30 min and 1, 2, 3, 6, 12, and 24 h after IV drug injection. Salivary flow rates were decreased significantly for 12 h after glycopyrrolate injection, compared with saline injection. The concentrations of immunologic and nonimmunologic defense factors were increased in the glycopyrrolate group, and differences between the groups were found for all factors (P < 0.05–0.001) except lysozyme and total salivary peroxidase. In contrast, because of the reduced flow rate, the output of all defense factors into the saliva was decreased after glycopyrrolate injection, compared with saline injection. Glycopyrrolate thus decreases the output of salivary host defense factors into the oral cavity. Implications Glycopyrrolate induces long-lasting hyposalivation and decreases the secretion of salivary immunologic and nonimmunologic defense factors in healthy volunteers.

The Use of Metoprolol and Glycopyrrolate to Prevent Hypotensive/Bradycardic Events During Shoulder Arthroscopy in the Sitting Position Under Interscalene Block

Sudden profound hypotensive and/or bradycardic events (HBE) have been reported in >20% of patients undergoing shoulder arthroscopy in the sitting position under interscalene block anesthesia.Retrospective studies suggest that the administration of beta-blockers is safe and may decrease the incidence of these episodes. We performed a randomized, prospective study to evaluate prophylaxis of these events. One hundred fifty patients were randomized to one of three groups (placebo; prophylactic metoprolol to achieve a heart rate <60 bpm or a maximal dose of 10 mg; or prophylactic glycopyrrolate to achieve a heart rate >100 bpm or a maximal dose of 6 [micro sign]g/kg) immediately after the administration of the interscalene block. Blood pressure control was achieved with IV enalaprilat as needed. The incidence of HBE was 28% in the placebo group versus 5% in the metoprolol group (P = 0.004). The rate of 22% in the glycopyrrolate group was not significantly different from placebo. Preoperative heart rate and arterial blood pressure, intraoperative sedation score, IV fluids, and enalaprilat use were similar in those patients who had a HBE compared with those who did not. Many aspects of this clinical setting are similar to tilt-Table testingfor patients with recurrent vasovagal syncope, in which beta-adrenergic blockade with metoprolol has also been shown to be effective. We conclude that the Bezold-Jarisch reflex is the most likely mechanism for these events. Implications: Episodes of acute hypotension and bradycardia occur during shoulder arthroscopy in the sitting position under interscalene block. In this study, we demonstrate that metoprolol, but not glycopyrrolate, markedly decreases the incidence of these episodes when given prophylactically immediately after the administration of the block. (Anesth Analg 1998;87:1320-5)

The effects of atropine and glycopyrrolate on heart rates in conscious mature goats.

The effects of intravenously administered atropine (0.2 mg/kg) and glycopyrrolate (0.01 mg/kg) on heart rate were studied in 10 conscious mature goats. In a drug cross-over fashion, either atropine, glycopyrrolate, or 0.9% saline solution was administered using the same volume (0.05 mL/kg). Atropine and glycopyrrolate caused a significant increase in heart rate (P < .05), whereas saline solution (0.09%) did not. The mean percent changes in heart rate from baseline were similar for atropine and glycopyrrolate up to 14 minutes after administration. Thereafter, glycopyrrolate had a significantly greater mean change in heart rate than atropine, ie, up to 29 minutes (P < .05). Within the atropine group, the mean percentage changes in heart rate became significantly lower compared with the initial increase (1 minute) starting at 11 minutes. For the glycopyrrolate group, the mean percent changes became significantly lower starting at 27 minutes. Glycopyrrolate and atropine had a mean percentage change in heart rate of greater than 1.0%, up to 31 and 22 minutes, respectively. At the doses used, glycopyrrolate had longer duration of action than atropine but the magnitude of increase was similar.

Effects of Combined Treatment With Glycopyrrolate and Albuterol in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Study objective: To investigate whether the addition of a single aerosolized dose of glycopyrrolate leads to a greater improvement in pulmonary function than treatment with albuterol alone for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Design: Prospective, randomized, blinded, controlled study. Fifty-seven patients with acute exacerbation of COPD were entered into the study. All patients received three aerosol treatments. Patients were randomized to recive 2 mg aerosolized glycopyrrolate (combination therapy group) or aerosolized placebo in addition to their first 2.5-mg of aerosolized albuterol alone for the next two treatments. Setting: Urban teaching hospital emergency department. Results: We found no difference in pretreatment 1-second fractional expired volume (FEV1) between the control and glycopyrrolate groups. There was no significant difference in the absolute value of the FEV1 at 1 hour or at 3 hours between the two groups; however, patients who received combination therapy had a greater percent increase from the pretreatment value of FEV1(56%) as measured in milliliters than did control patients (19%; P =.008). Conclusion: The combination of glycopyrrolate and albuterol produces a greater improvement in FEV1 than does albuterol alone in the treatment of patients with acute exacerbation of COPD. [Cydulka RK, Emerman CL: Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease.Ann Emerg Med April 1995;25:470-473.]

Anticholinergic prophylaxis does not prevent emesis following strabismus surgery in children

One hundred and twenty-one children were studied in this prospective, randomized double-blind, placebo-controlled comparison of the effectiveness of anticholinergic prophylaxis for the prevention of emetic symptoms following strabismus surgery. The children were allocated to three groups, to receive placebo (n = 40), glycopyrrolate (n = 40) or atropine (n = 41). The incidence of intraoperative oculocardiac reflex (OCR) and of postoperative emetic symptoms for 24 h was recorded. The incidence of OCR was 55% in the placebo group compared with 5% and 2% in the glycopyrrolate and atropine groups respectively (P < 0.05). Thirty percent (12/40) of patients in the placebo group, 25% (10/40) in the glycopyrrolate group, and 22% (9/41) in the atropine group experienced nausea and/or vomiting (difference not significant). It is concluded that prophylactic administration of anticholinergic agents during strabismus surgery in children despite being effective against the occurrence of the oculocardiac reflex, does not reduce the incidence of emetic symptoms.

Effects of Combined Treatment With Glycopyrrolate and Albuterol in Acute Exacerbation of Asthma

Study objective: Recent reports suggest that glycopyrrolate is as effective as metaproterenol in the treatment of acute bronchospasm. The purpose of this study was to investigate whether the addition of a single aerosolized dose of glycopyrrolate to an albuterol regimen results in a greater improvement in pulmonary function than treatment with an albuterol regimen alone in patients with acute asthma. Design: Prospective, randomized, double-blinded, controlled study. All patients received a total of three aerosol treatments and 60 mg solumedrol IV push. Patients were randomized to receive 2 mg aerosolized glycopyrrolate (combination therapy) or aerosolized placebo (control) in addition to their first 2.5 mg albuterol aerosol treatment. Both groups received 2.5 mg aerosolized albuterol alone for the next two treatments. Setting: An urban teaching hospital emergency department. Participants: One hundred twenty-five patients with acute exacerbation of asthma were entered into the study. Main results: There was no difference in pretreatment forced expiratory volume (one second) (FEV 1) between the control group and the glycopyrrolate group. Asthmatic patients receiving combination therapy had less of a change in FEV 1 (52%) than did control patients (82%, P < .05). Conclusion: The combination of glycopyrrolate and albuterol does not appear to be beneficial over albuterol alone in treating patients with acute exacerbation of asthma. [Cydulka RK, Emerman CL: Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of asthma. Ann Emerg Med February 1994;23:270-274.]

Split-dose atropine versus glycopyrrolate with neostigmine for reversal of gallamine-induced neuromuscular blockade

The effects of a split-dose of atropine sulphate versus a single dose of glycopyrrolate given with neostigmine for the reversal of gallamine-induced neuromuscular blockade were studied in 55 patients undergoing gynaecological surgery. The patients were randomized to receive either a single dose of glycopyrrolate (7 micrograms.kg-1) or two doses of atropine (8 micrograms.kg-1 each), given with an interval of 1 min. There were no differences between the two methods with respect to percentage heart rate changes, salivation or arousal time. Four patients demonstrated cardiac arhythmias in the atropine group, whereas none occurred in the glycopyrrolate group (P less than 0.05). It is concluded that a split-dose of atropine has similar chronotropic effects to a single dose of glycopyrrolate for the reversal of gallamine-induced neuromuscular blockade. However, the finding of a higher incidence of cardiac arrhythmias in the atropine group suggests that this reversal regime should be reserved for patients without cardiac disease.

Organophosphate poisoning

Organophosphate poisoning occurs worldwide and often requires admission to an ICU. Grading of patients may be of value to identify high-risk cases but this has never been prospectively evaluated. Conventional treatment with atropine may lead to CNS toxicity, although control of secretions may still be inadequate. We conducted a randomized, controlled trial in 44 patients to compare atropine with glycopyrrolate, a drug that may provide better control of secretions and does not cross the blood-brain barrier. Grading was performed prospectively and compared to outcome. Thirty-nine cases were evaluated (atropine 22, glycopyrrolate 17); the treatment groups were comparable at baseline. No differences could be detected in outcome except for a trend to fewer respiratory infections in the glycopyrrolate group. Thus, treatment with atropine and glycopyrrolate was equally effective. A grading of serious was associated with ventilation, complications, and a prolonged ICU stay. A revised simplified grading is proposed.

Modification of Chronotropic Response to Anticholinergics by Halogenated Anaesthetics in Children

Cardiac rate and rhythm changes were studied in 40 children after intravenous injection of atropine or glycopyrrolate following induction of anaesthesia with halothane and enflurane. Premedication was standardized in all groups and ventilation controlled to achieve normal end tidal carbon dioxide. Heart rate increased in all cases following anticholinergic medication and the increase in heart rate was significantly higher in children receiving halothane anaesthesia as compared to those given enflurane. There was no significant difference between atropine and glycopyrrolate groups. There was no difference in frequency of occurrence of junctional tachycardia, which was the only arrhythmia observed, in the four groups studied. Our findings suggest that, in clinical situations where development of marked tachycardia is a concern, the combination of enflurane and anticholinergic drugs offers an advantage over the combination of halothane and anticholinergic drugs in paediatric patients.

Effects of Glycopyrrolate and Cimetidine on Gastric Volume and Acidity in Patients Awaiting Surgery

SUMMARY Glycopyrrolate or cimetidine was administered before operation to patients undergoing elective surgery. After the induction of anaesthesia, the stomach contents were retrieved and the volume and pH measured. Neither drug diminished the volume of gastric contents compared with control. Glycopyrrolate produced little diminution in hydrogen ion concentration. Cimetidine caused a marked increase in pH with a mean [H + ] 3.2 × 10 −3 g litre 1 compared with 1.4 × 10 2 g litre 1 in the controls and 1.1 × 10 2 g litre 1 in the glycopyrrolate group. Seventy-seven per cent of the patients receiving cimetidine had a pH greater than 2.5.

EFFECTS OF GLYCOPYRROLATE AND CIMETIDINE ON GASTRIC VOLUME AND ACIDITY IN PATIENTS AWAITING SURGERY

Glycopyrrolate or cimetidine was administered before operation to patients undergoing elective surgery. After the induction of anaesthesia, the stomach contents were retrieved and the volume and pH measured. Neither drug diminished the volume of gastric contents compared with control. Glycopyrrolate produced little diminution in hydrogen ion concentration. Cimetidine caused a marked increase in pH with a mean [h+] 3.2 x 10(-3) g litre-1 compared with 1.4 x 10(-2) g litre-1 in the controls and 1.1 x 10(-2) g litre-1 in the glycopyrrolate group. Seventy-seven per cent of the patients receiving cimetidine had a pH greater than 2.5.