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.     

Glycopyrrolate compared with atropine in association with ketamine anaesthesia

Atropine and glycopyrrolate given intravenously before the induction of a ketamine anaesthesia to diminish salivary secretion were compared for their effect on psychotomimetic side-effects, awakening time and heart rate. Though atropine is a tertiary amine that crosses the blood-brain barrier, which glycopyrrolate as a quaternary ammonium compound does not, it did not increase the incidence of psychotomimetic side-effects nor did it significantly prolong the awakening time after ketamine anaesthesia. During intubation the increase in heart rate was significantly higher following atropine than following glycopyrrolate.     

The use of dexmedetomidine during laryngoscopy, bronchoscopy, and tracheal extubation following tracheal reconstruction

We report the use of dexmedetomidine for laryngoscopy, rigid bronchoscopy, and tracheal extubation in the operating room in two children who had undergone tracheal reconstruction 1 week previously. Dexmedetomidine in combination with propofol provided appropriately deep anesthesia during these brief but stimulating procedures without cardiovascular or respiratory depression.     

Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

The pharmacokinetics and some pharmacodynamic properties of atropine, glycopyrrolate and scopolamine are reviewed. With the development of new analytical methods for drug determination, it is now possible to measure relatively low concentrations of these drugs in biological fluids and, consequently, some new kinetic data have been collected. Following intravenous administration, a fast disappearance from the circulation is observed and due to a high total clearance value their elimination phase half–lives vary from 1 to 4 h. All these agents are nonselective muscarinic receptor antagonists, but their actions on various organ systems with cholinergic innervation show considerable diversity. The cardiovascular effects are of short duration; other peripheral muscarinic effects and CNS effects can last up to 8 h or even longer. Differing from atropine and scopolamine, glycopyrrolate as a quaternary amine penetrates the biological membranes (blood–CNS, placental barriers) slowly and incompletely, making it the drug of choice for elderly patients with coexisting diseases and for obstetric use. Similarly, its oral absorption is slow and erratic, and hence it cannot be used as an oral premedicant. Atropine, scopolamine and glycopyrrolate have a definitely faster absorption rate, when injected into the deltoid muscle compared with administration into the gluteal or vastus lateralis muscles. There appear to be significant differences in the metabolism and renal excretion of these agents. Scopolamine is apparently excreted into the urine mainly as inactive metabolites, nearly half of the atropine dose administered is recovered in the urine as the parent drug or as active metabolites and about 80% of glycopyrrolate is excreted as unchanged drug or active metabolites. However, despite the diversity in some pharmacokinetic features, the differences in clinical effects are not very prominent in healthy patients.     

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.     

Atropine vs Glycopyrrolate During Reversal of Pancuronium Block in Patients Anaesthetized with Halothane

Atropine 0.015 mg kg-1 and glycopyrrolate 0.0075 mg kg-1 were compared as antimuscarinic agents during reversal of pancuronium block with neostigmine 0.03 mg kg-1 in 30 patients anaesthetized with thiopental-N2O-halothane and undergoing minor surgery. In patients treated with atropine-neostigmine, the frequencies of bradycardia and junctional rhythm were relatively high and about the same as those reported by us previously in patients anaesthetized with thiopental-N2O-fentanyl. As in our previous study, glycopyrrolate seemed to have advantages over atropine during reversal of pancuronium block: the incidences of bradycardia and junctional rhythm were significantly less in patients treated with glycopyrrolate. Recovery from anaesthesia, as assessed by the awakening after discontinuation of N2O and halothane administration, and the incidence of postoperative nausea and vomiting, were not significantly different between the atropine and glycopyrrolate groups.     

Comparison of remifentanil and alfentanil during anaesthesia for patients undergoing direct laryngoscopy without intubation

Background. Remifentanil and alfentanil are opioids often usedduring direct laryngoscopy (DL). This prospective, randomizedstudy compared these agents with respect to haemodynamic andBispectral Index (BIS) responses, glottic visualization, andrapidity of recovery (spontaneous ventilation, eye opening)in DL without intubation. Methods. A total of 60 patients undergoing DL were randomizedinto two groups: remifentanil (R) and alfentanil (A). Anaesthesiawas induced with propofol 2.5 mg kg^–1 and the opioid wasadministered 1 min later (R=2 µg kg^–1 or A=30 µgkg^–1 over 30 s). DL was commenced 1 min after (correspondingto 3 min after the beginning of induction). Glottic visualization,opioid and/or propofol re-injection, spontaneous ventilationrecovery, and eye opening were recorded. Results. During DL, mean arterial pressure (MAP) increased by6% in the R group vs 20% in the A group (P<0.05) when comparedwith post-induction values without affecting heart rate or BIS.No significant difference was observed between groups with respectto glottic exposure, opioid and/or propofol re-injection, andspontaneous ventilation recovery (mean (SEM) 3.8 (0.6) min,R group vs 3.2 (0.7) min, A group, NS) or eye opening (7.1 (1.1)min, R group vs 7.4 (0.9) min, A group, NS). Thirty minutesafter postanaesthesia care unit (PACU) admission, MAP returnedto its pre-induction value in the R group (104 (3) vs 109 (3)at baseline, NS), whereas in the A group MAP remained significantlylower at this time point (96 (4) vs 106 (3) at baseline, P<0.05). Conclusion. This study showed that only remifentanil preventedMAP increase without adverse effects such as bradycardia duringDL, and prevented MAP decrease 30 min after PACU admission. Br J Anaesth 2003; 91: 421–3     

Thoracolumbar epidural anaesthesia blocks the circulatory response to laryngoscopy and intubation

Laryngoscopy and endotracheal intubation cause a stress reaction resulting in an increase in heart rate and systemic blood pressure. This haemodynamic response is considered to be due to a sympathetic discharge caused by stimulation of the upper respiratory tract. This stress reaction during laryngoscopy and endotracheal intubation was studied in patients with total thoracolumbar epidural anaesthesia (EDA). Nine patients with thoracolumbar EDA including at least the segments T1 to L2 were compared to seven patients without EDA during induction of general anaesthesia. The epidural anaesthesia was achieved with 2% mepivacaine with adrenaline. General anaesthesia was induced with thiopentone 4-5 mg/kg followed by 100 mg suxamethonium. The highest blood pressure value during the first 2 min after intubation was compared to the value immediately before intubation. The epidural anaesthesia caused a reduction of the mean arterial blood pressure (MAP) by 25%, and a reduction of the heart rate (HR) by 7%, but neither the induction with thiopentone nor the laryngoscopy and intubation caused any changes in mean arterial blood pressure or heart rate. However, in the control group MAP increased 29% and HR 16% following intubation. Thus, the T1-L2 epidural anaesthesia with 2% mepivacaine with adrenaline blocked the blood pressure reaction to laryngoscopy and intubation, and consequently the efferent sympathetic nervous system was completely blocked.     

Rigid bronchoscopy for foreign body removal: anaesthesia and ventilation

Foreign body aspiration is a leading cause of death in children 1-3 years old, although mortality is low for children who reach the hospital. Presenting symptoms of an inhaled foreign body depends on time since aspiration. Immediately after inhalation the child starts to cough, wheeze, or have laboured breathing. If the early signs are missed, the child usually presents with fever and other signs and symptoms of chest infection. A plain chest X-ray has relatively low sensitivity and specificity for inhaled foreign body. The gold standard for diagnosis and management of this condition is rigid open tube bronchoscopy under general anaesthesia. For late presentations, time should be taken to fast the child and complete a thorough evaluation before bronchoscopy. The procedure should be performed in a well-equipped room with at least two anaesthesiologists, one with paediatric experience, in attendance. Most experienced anaesthesiologists prefer inhalational rather than intravenous induction of anaesthesia and a ventilating bronchoscope rather than intubation. Equally good results have been reported with spontaneous ventilation or positive pressure ventilation; jet ventilation is not advocated for foreign body removal in children.     

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.     

A prospective randomised controlled trial of capnography vs. bronchoscopy for Blue Rhino percutaneous tracheostomy

A crucial step for successful percutaneous tracheostomy is the introduction of the needle and guide wire into the trachea. Capnography has recently been proposed as one way to confirm tracheal needle placement. In this randomised controlled study, we used capnography in 26 patients and bronchoscopy in 29 patients to confirm needle placement for percutaneous tracheostomy using Blue Rhino kit. The operating times and the incidence of peri-operative complications were similar for both groups. Capnography proved to be as effective as bronchoscopy in confirming correct needle placement.