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Does vecuronium accumulate in the renal transplant patient?

Twenty ASA physical status Class III patients undergoing cadaver renal transplantation were studied. After 90 per cent T1 recovery, as determined by train-of-four measurement, from 1.0 mg.kg-1 succinylcholine to facilitate tracheal intubation, nine patients received atracurium 0.25 mg.kg-1 (Group I) and 11 patients received vecuronium 0.05 mg.kg-1 (Group II) intravenously. The following measurements were made: time to maximum block onset (first dose Max), injection to start of recovery (start REC1), injection to 25 per cent T1 twitch recovery (REC 251), injection to 75 per cent T1 (REC 75(1], injection to 90 per cent T1 (REC 90(1] and time from 25-75 per cent recovery T1 (REC 25-75(1]. Maximum blockade (Max block 1) was also measured. At 90 per cent T1 recovery, if time permitted, an identical dose of the appropriate relaxant was administered. Time from second dose to onset of maximum block (second dose Max) and 90 per cent recovery after second dose (REC 90(2] were then measured. At the conclusion of surgery, neuromuscular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.5 mg. One way ANOVA was performed to determine significance between the groups and a p less than 0.05 was considered significant. A paired t test was also performed between REC 90(1) and REC 90(2) for atracurium and vecuronium respectively. A p less than 0.05 was again considered significant. Measurement of first dose Max, start REC1, REC25(1), REC 75(1), REC 90(1), REC 25-75(1) and Max block 1 revealed no difference between the patients receiving an initial dose of atracurium and those receiving vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effects of different doses of edrophonium antagonism of mivacurium-induced neuromuscular block in the presence of nitrous oxide, propofol, and alfentanil anesthesia].

PURPOSE: The purpose of this study was to determine the dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block. METHOD: Seventy-five ASA physical status I or II adults were given mivacurium 0.15 mg.kg-1 followed by an infusion (7 micrograms.kg-1.min-1) during alfentanil-propofol-N2O anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 20 sec and the response of the adductor digiti minimi was recorded (Relaxograph NMT-100, DATEX, Helsinki, Finland). Mivacurium infusion was adjusted at five minutes intervals in order to keep the height of the first twitch in TOF (T1) at 5% of its control value. At the end of surgery, the mivacurium infusion was stopped and edrophonium 0.0, 0.05, 0.1, 0.5 or 1.0 mg.kg-1 combined respectively with glycopyrrolate 0.0, 0.0005, 0.001, 0.005 or 0.01 mg.kg-1 were administered by random allocation. RESULTS: All four edrophonium doses tested were statistically different from placebo with regard to time to attain a TOF ratio (fourth twitch in TOF/T1) = 0.7 (0.05:780 +/- 179, 0.1:727 +/- 216, 0.5:547 +/- 287 and 1.0:640 +/- 236 vs 0.0 mg.kg-1:1089 +/- 323 sec P < 0.05). Does of 0.1, 0.5 and 1.0 mg.kg-1 permitted faster recovery time of T1 from 10 to 95% (T10-95) (567 +/- 236, 419 +/- 166, 555 +/- 288 vs 861 +/- 224 sec P < 0.05) and from 25 to 75% (T25-75) (253 +/- 121, 147 +/- 92, 217 +/- 175 vs 429 +/- 154 sec P < 0.05) than did placebo. However, data showed considerable variability for all neuromuscular indices, no matter the dose of edrophonium used. CONCLUSION: Edrophonium in doses of 0.1 mg.kg-1 and higher permitted faster recovery of all indices from a mivacurium-induced block during alfentanil-propofol-N2O anaesthesia than did placebo.

Adult↗

Postoperative reparalysis after rocuronium following nebulized epinephrine.

PURPOSE: We report a case of postoperative reparalysis in the recovery room, following nebulized epinephrine. The patient was pharmacologically reversed with edrophonium after paralysis with rocuronium. CLINICAL FINDINGS: A 12-yr-old girl developed postoperative reparalysis following the intraoperative administration of rocuronium. A total of 0.92 mg.kg-1 rocuronium was administered. After surgery, pharmacological reversal was achieved with 20 mg edrophonium with 0.15 mg atropine sulfate iv 35 min after the last administration of rocuronium. Muscular relaxation was monitored using an ulnar peripheral nerve stimulator (PNS). After reversal, a full train-of-four and sustained tetanus at 50 Hz were present. In the recovery room, following nebulized epinephrine, the patient became apneic. The patient was paralyzed and an ulnar PNS demonstrated only one faint twitch. The paralysis was reversed with 1.5 mg neostigmine with 0.3 mg glycopyrrolate. CONCLUSION: Postoperative reparalysis following rocuronium may be a cause of postoperative respiratory distress. The definitive diagnosis is made using PNS and observing the response to pharmacological reversal. Nebulized epinephrine may have a previously undescribed role in the development of postoperative reparalysis.

Administration, Inhalation↗

Sevoflurane with remifentanil allows rapid tracheal intubation without neuromuscular blocking agents.

PURPOSE: After inhalational induction with sevoflurane, we compared the effects of adding remifentanil 1 microg x kg(-1) or remifentanil 2 microg x kg(-1) on conditions for tracheal intubation without neuromuscular blocking agents. METHODS: Before anesthetic induction, all patients were given 0.2 mg of glycopyrrolate iv to counteract the bradycardic effects of remifentanil. Two minutes after inhalational induction with 8% sevoflurane and 50% nitrous oxide, 56 female patients with normal airways scheduled for gynecologic surgery were randomized to receive remifentanil 1 or 2 microg x kg(-1) in a double-blind fashion. One minute later, laryngoscopy was initiated for tracheal intubation. Conditions for tracheal intubation and hemodynamic response to tracheal intubation were assessed. RESULTS: Tracheal intubation was successful in all patients. The incidence of post-intubation coughing was lower in the remifentanil 2 microg x kg(-1) group compared to remifentanil 1 microg x kg(-1) group (11% vs 39%, P <0.02). Optimal intubation conditions were also higher in the remifentanil 2 microg x kg(-1) group at 89% vs 54% (P <0.01). However, the higher dose of remifentanil also resulted in a greater decrease in mean arterial pressure (P <0.05). CONCLUSIONS: The addition of remifentanil after sevoflurane induction allows for rapid tracheal intubation without neuromuscular blocking agents. The higher dose of remifentanil results in improved conditions for tracheal intubation but also caused a greater decrease in mean arterial pressure. Tracheal intubation using sevoflurane and remifentanil may be an alternative to traditional tracheal intubation with neuromuscular blocking agents.

Adjuvants, Anesthesia↗

Successful implementation of perioperative beta-blockade utilizing a multidisciplinary approach.

PURPOSE: To describe how we implemented a protocol for perioperative beta-blockade in patients with or at risk of coronary artery disease (CAD) undergoing major non-cardiac surgery and to present our results. METHODS: After institutional approval, from May 1999 to April 2001, patients with surgical and medical indications (CAD as indicated by previous myocardial infarction, typical angina or atypical angina with a positive stress test or at least two risk factors for CAD: age 65 yr, hypertension, smoking, high cholesterol, diabetes mellitus) for perioperative beta-blockade were identified preoperatively by anesthesiology and referred to the General Internal Medicine Service (MED). MED initiated patients on outpatient beta-blockers. The intraoperative anesthetic management was left to the discretion of the anesthesiologist. In the postanesthesia care unit (PACU), patients received iv metoprolol according to hemodynamic criteria. Postoperatively, patients were followed by MED for adverse cardiac events. RESULTS: Sixty-nine patients received perioperative beta-blockade. Preoperatively, 60% were started on metoprolol, 39% on atenolol and 1% on propranolol. In PACU, 42%, 9% and 38% of patients were given iv metoprolol 0, 5 and 10 mg respectively. One patient was given glycopyrrolate in the PACU for bradycardia and none received vasoactive or inotropic agents. Three patients (4.3%) had postoperative cardiac events. CONCLUSIONS: With close collaboration between anesthesiologists, internists, PACU nurses and family physicians, a strategy for perioperative beta-blockade was implemented successfully in patients with cardiac risks. Beta-blockade was associated with few side effects and morbidities.

Adrenergic beta-Antagonists↗

Different properties of the bradycardia produced by neostigmine and edrophonium in the cat.

PURPOSE: The bradycardia produced by neostigmine and edrophonium was examined according to its relation to cholinesterase inhibition and to its sensitivity to block by muscarinic receptor antagonists. For comparison, the ability of muscarinic antagonists to block the bradycardia produced by electrical stimulation of the vagus nerve was determined. METHODS: Cats were anaesthetized, vagotomized and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. The right vagus nerve was isolated for electrical stimulation. The muscarinic antagonists used were atropine, glycopyrrolate, pancuronium, gallamine, and AFDX-116. RESULTS: Neostigmine produced a dose-dependent decrease in cholinesterase activity which reached a plateau at a cumulative dose of 0.16 mg.kg-1 (ED50 0.009 +/- 0.003 mg.kg-1). Neostigmine produced a dose-dependent decrease in heart rate with the dose-response relationship (ED50 0.1 +/- 0.01 mg.kg-1; P = 0.0006) shifted to the right of that for the inhibition of cholinesterase activity. In contrast to the anticholinesterase effect, the bradycardic effect did not reach a plateau and continued to increase even at doses at which the cholinesterase inhibition was maximal. The maximal decrease in heart rate when the heart was still in sinus rhythm was by 81 +/- 13 bpm (49 +/- 7% of baseline), which was produced by a dose of 0.32 mg.kg-1. Edrophonium produced dose-dependent decreases in cholinesterase activity and heart rate, which were highly correlated (correlation coefficient r = 0.99, P < 0.0001). The ED50 of the reduction in heart rate (0.9 +/- 0.18 mg.kg-1) and cholinesterase activity (0.89 +/- 0.12 mg.kg-1) produced by edrophonium were similar. Moreover, the reduction in heart rate and cholinesterase activity produced by edrophonium reached a plateau at the same dose (6.4 mg.kg-1). At this dose, heart rate decreased by 22 +/- 2 bpm (14.6 +/- 0.9% of baseline). Compared to the bradycardia produced by stimulation of the vagus nerve, that produced by neostigmine was blocked by muscarinic antagonists at significantly lower doses while that produced by edrophonium was blocked at similar doses. CONCLUSIONS: The neostigmine-induced bradycardia is poorly correlated with cholinesterase inhibition compared to that produced by edrophonium, and has a higher sensitivity to muscarinic receptor antagonists compared to that produced by edrophonium or vagus nerve stimulation. These results are consistent with the hypothesis that the neostigmine-induced bradycardia is, in part, the result of neostigmine directly activating cholinergic receptors within the cardiac parasympathetic pathway. The bradycardia produced by edrophonium may be accounted for solely by an anticholinesterase action.

Acetylcholine↗

Foreign body aspiration following unconventional use of a metered dose inhaler.

PURPOSE: Aspiration of a foreign body may be life-threatening. This report describes laryngeal obstruction after inhalation of a piece of a Turbuhaler which resulted from a patient tampering with the device. CLINICAL FEATURES: A 27-yr-old man disassembled a Turbuhaler and inadvertently aspirated a plastic dispensing medication disc (22 mm diameter) while attempting to inhale the remnant terbutaline sulfate which accumulated on it. Although the patient was hoarse, he was not in acute respiratory distress. X-ray revealed the disc lodged in the larynx below the vocal cords. The patient was immediately transferred to an operating theatre, and a drying agent (glycopyrrolate), judicious sedation (midazolam and fentanyl) and O2 were administered. The airway was anesthetized with lidocaine 4% delivered using high-flow O2 through an atomizer. Direct laryngoscopy revealed a partially obstructed view of the disc lodged distal to the vocal cords which was inaccessible for retrieval. Loss of consciousness was subsequently induced by spontaneous mask ventilation with sevoflurane (in O2). The airway was visualized using a suspension laryngoscope and the foreign body was removed with grasping forceps. The patient was awakened, transferred to the ICU and given 4 mg decadron i.v. every eight hours (two doses). Laryngoscopy prior to discharge indicated good mobility of the vocal cords and normal glottic structure. CONCLUSION: Aspiration of a foreign body is a potentially life-threatening situation requiring coordination between anesthesiologist, surgeon, and nursing staff. Anesthetic goals include avoidance of upper airway obstruction and maintenance of adequate ventilation while the foreign body is retrieved. Provisions must be made for tracheostomy if these goals cannot be realized.

Adult↗

Asystole after intravenous neostigmine in a heart transplant recipient.

PURPOSE: To describe a heart transplant recipient who developed asystole after administration of neostigmine which suggests that surgical dennervation of the heart may not permanently prevent significant responses to anticholinesterases. CLINICAL FEATURES: A 67-yr-old man, 11 yr post heart transplant underwent left upper lung lobectomy. He developed asystole after intravenous administration of 4 mg neostigmine with 0.8 mg glycopyrrolate for reversal of the muscle relaxant. He had no history of rate or rhythm abnormalities either prior to or subsequent to the event. CONCLUSION: When administering anticholinesterase medications to heart transplant patients, despite surgical dennervation, one must be prepared for a possible profound cardiac response.

Aged↗

[Ondansetron versus droperidol. Postoperative treatment against nausea and vomiting. Comparison of action, adverse effects and acceptance by gynecologic inpatients].

INTRODUCTION: Ondansetron is more effective than a placebo in treating postoperative nausea and vomiting (PONV), but it has not been proved to be superior to established antiemetics for prophylaxis or therapy. We compared ondansetron vs droperidol for the treatment of PONV. METHODS: Our prospective, randomized double-blind study was performed between 15 October 1992 and July 1993; it included 271 gynaecological ASA I-III inpatients who had been operated on under general anaesthesia with intubation. Patients were excluded if: there was no informed consent; it was an ambulatory or emergency operation; the patient was pregnant or breast feeding; allergies were being treated with antihistamines; drug addiction was present or convulsions or Parkinson's disease; any pre- or intraoperative antiemetic medication had been administered. All patients wishing an antiemetic and/or suffering from at least one emetic episode during the first 24 h postoperatively received either 8 mg ondansetron or 1.25 mg droperidol from identical 4 ml ampoules intravenously. The verbal nausea score (1 = none, 2 = mild, 3 = moderate, 4 = severe) was recorded every 30 min for 4 h, then before and 2 h after each antiemetic dose. All emetic episodes and the interval between administration and effect were also noted. Patients were interviewed 36-48 h postoperatively on subjective effects, side-effects and individual acceptance. After oral premedication with diazepam, anaesthesia was induced with thiopental, in a few cases with etomidate or propofol. Relaxation was achieved with pancuronium or atracurium and, when indicated, with succinylcholine. Muscular relaxation was antagonized with neostigmine and glycopyrrolate. Gastric content was aspirated once after intubation. Anaesthesia was maintained with nitrous oxide/oxygen, enflurane, halothane or isoflurane and fentanyl up to 0.3 mg. Statistical evaluation was performed by the unpaired Student's t-test and the Mann-Whitney U test. Categoric variables were examined by the chi 2 test. Significance was defined as P < 0.05. RESULTS: Of 271 patients, 100 (37%) experienced PONV. The groups were statistically comparable with respect to demographic data, type and duration of operation, emesis record, perioperative uterotonic medication. Twenty patients in the ondansetron group and 27 in the droperidol group received the first antiemetic within 2 h, the other patients up to 17 h after extubation. Nausea scores and emetic episodes were identical before antiemetic medication. The reduction of these parameters after medication was similar. Complete response over 6 h was 60% in the ondansetron and 68% in the droperidol group. In both groups the first medication failed in 4 cases during the initial 2 h. Twenty of the ondansetron and 16 of the droperidol patients needed a second dose; among these 2 and 4, respectively, a third ampoule. No rescue medication was necessary over 24 h and a mean of 1.4 ampoules was administered in both groups. Onset and quality of emetic action were identical in both groups. It was not possible to evaluate 25 interviews due to linguistic or amnestic problems. Multiple side-effects were noted frequently. Injection pain was reported significantly more often in the droperidol, pruritus in the ondansetron group. Ninety-three percent of the ondansetron and 85% of the droperidol patients opted for the same drug for future PONV treatment. CONCLUSIONS: Ondansetron (8 mg) and droperidol (1.25 mg) proved to be equally effective when used as a postoperative antiemetic. Both drugs showed similar side-effects. Due to differences in methods it was difficult to compare our results to those obtained in other studies.

Adult↗

Cholinergic regulation of thyrotropin secretion in male rats.

The cold-stimulated thyrotropin (TSH) secretion in male rats was suppressed by muscarinic agonists, i.e. Oxa-22, McN-A-343 (an M1 agonist), oxotremorine (an M2 agonist) and methacholine (a quaternary compound). The inhibitory effect of Oxa-22 was antagonized by atropine, butylscopolamine and glycopyrrolate as well as by pirenzepine, an M1 antagonist and AF-DX 116, a new M2 antagonist. Various muscarinic antagonists were not active when given alone. Cytisine, a peripheral nicotinic agonist, was not active but nicotine significantly suppressed the cold-stimulated TSH secretion. Its effect was counteracted by mecamylamine but not by hexamethonium. The thyrotropin releasing hormone (TRH)-induced TSH secretion was not inhibited by Oxa-22, nicotine or methacholine. These results show that irrespective of the receptor subtype (muscarinic1 or muscarinic2, nicotinic), cholinergic activation inhibits the cold-stimulated TSH secretion. The results also suggest that this inhibitory effect is at the hypothalamic rather than the anterior pituitary level. The muscarinic action seems to occur outside the blood-brain barrier but the nicotinic action occurs inside this barrier.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes.

9-Amino-1,2,3,4-tetrahydroacridine (THA) has been reported to cause improvement in patients with senile dementia of the Alzheimer's type. We have examined some effects of THA in vitro and in vivo to define its mechanism of action. In vitro, THA inhibits acetylcholinesterase (AChE) (IC50 = 223 nM) and blocks [3H]AFDX-116 (M2) and [3H]telenzepine (M1) binding (IC50 s of 1.5 and 9.1 microM respectively). In vivo levels of THA were 10-fold higher in brain than plasma following 3.2 mg/kg i.p., a dose which was found to be active in reversing amnesia induced by scopolamine assessed in T-maze tests in rats and passive avoidance tests in mice. Additionally, these brain concentrations were above the IC50 of THA for AChE inhibition. THA (5.6-17.8 mg/kg i.p.) also elevated acetylcholine levels in the rat CNS. THA-induced side effects were blocked by the central muscarinic antagonist, scopolamine, but not by the peripheral antagonists methscopolamine and glycopyrrolate, nor by nicotinic antagonists. We conclude that brain AChE inhibition by THA is sufficient to explain its purported therapeutic activity in Alzheimer's disease and that its favorable brain/plasma distribution in vivo may account for its central cholinergic action without inducing the severe peripheral cholinergic effects typically seen with other AChE inhibitors.

Acetylcholinesterase↗

The effect of ondansetron on atracurium-induced neuromuscular blockade.

STUDY OBJECTIVE: To determine whether treatment with ondansetron, a new antiemetic drug, affects nondepolarizing neuromuscular blockade. DESIGN: Randomized, double-blind, prospective study. SETTING: Operating room at a university medical center. PATIENTS: 30 ASA physical status I and II patients scheduled for elective surgery. INTERVENTIONS: After the induction of anesthesia with midazolam 2 to 4 mg/kg, sodium thiopental 6 to 8 mg/kg, and fentanyl 4 to 8 micrograms/kg, the ulnar nerve was stimulated at the wrist through subcutaneous needle electrodes at a frequency of 0.15 Hz. The response to stimulation was measured and recorded with a force-displacement transducer applied to the thumb. Patients were randomized to one of three treatment groups. A steady baseline to ulnar nerve stimulation with nitrous oxide-oxygen-opioid-thiopental anesthesia was established. The first study group (Group 1) received a placebo, the second group (Group 2) received 8 mg of ondansetron, and the third group (Group 3) received 16 mg of ondansetron as an intravenous infusion over 5 minutes. Patients were then given incremental doses of atracurium 0.05 mg/kg at 3-minute intervals to establish approximately 95% twitch inhibition so as to construct a dose-response curve. An atracurium infusion was then begun to maintain a constant degree of neuromuscular blockade. At the end of surgery, patients were allowed to recover spontaneously, or pharmacologic antagonism of residual neuromuscular blockade was achieved with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg. Mechanomyographic response to train-of-four stimuli (2 Hz for 2 seconds) every 20 seconds was monitored during the atracurium infusion and recovery from neuromuscular blockade. MEASUREMENTS AND MAIN RESULTS: Log dose-response curves were determined for the study groups and compared using analysis of variance (ANOVA). The 50%, 75%, and 95% effective doses (ED50, ED75, and ED95) were calculated from the equation describing the log dose-response. Maintenance infusion rates were determined, and the neostigmine-accelerated recovery index of 25% to 75% was measured for each group. The results were compared using ANOVA. There were no significant differences among the treatment groups with respect to maintenance infusion rate (7.8 +/- 1.8 micrograms/kg/min for Group 1, 7.7 +/- 2.5 micrograms/kg/min for Group 2, and 7.3 +/- 2.3 micrograms/kg/min for Group 3) or neostigmine-accelerated recovery interval of 25% to 75% (4.5 +/- 2.3 minutes, 4.4 +/- 3.1 minutes, 6.6 +/- 3.9 minutes in Groups 1, 2, and 3, respectively). The log dose-response data for Groups 1, 2, and 3 did not differ significantly (p = 0.068), and the calculated ED95 in each treatment group demonstrated no dose-related change (0.254 +/- 0.022, 0.279 +/- 0.033, and 0.240 +/- 0.022 for Groups 1, 2, and 3, respectively). CONCLUSIONS: Ondansetron is an antiemetic drug that can be used in the perioperative period without concern for potentiation of nondepolarizing neuromuscular blockade, change in atracurium maintenance dose, or change in rate of neostigmine-induced recovery from neuromuscular blockade with atracurium.

Adult↗

Comparison of neuromuscular, cardiovascular, and histamine-releasing properties of doxacurium and pipecuronium.

STUDY OBJECTIVES: To determine the neuromuscular, cardiovascular, and histamine releasing properties of doxacurium and pipecuronium at three times effective ED95 doses (3XFD95). DESIGN: Prospective, randomized clinical trial of adult patients. SETTING: University teaching hospital. PATIENTS: 20 ASA status I and II adult patients. INTERVENTIONS: Subjects were anesthetized with thiopental sodium, fentanyl, and nitrous oxide and oxygen (N2O:O2). Plasma samples were taken preoperatively, after thiopental, and 2 and 5 minutes after doxacurium 75 micrograms/kg or pipecuronium 123 micrograms/kg were given for the determination of histamine levels. The ulnar nerve was stimulated via surface electrodes using train-of-four stimulation at 0.1 Hz. The force of contraction of adductor pollicis was recorded using a mechanomyograph. Recovery of the twitch response was followed and, if necessary, neuromuscular block was antagonized with neostigmine and glycopyrrolate. MEASUREMENTS AND MAIN RESULTS: Three patients in the doxacurrium group and one patient in the pipecuronium group exhibited a marked increase in plasma histamine levels. In both groups statistically significant changes were seen in heart rate (HR) measurements (p < 0.02). Doxacurium had a slower onset than pipecuronium [3.1 +/- 0.2 min vs. 1.8 +/- 0.1 min (p < 0.0003)] and a more rapid recovery [72 +/- 8 min vs. 123 +/- 9 min (p < 0.01)]. CONCLUSION: Neither drug caused a clinically significant change in HR or histamine release. In the doses chosen for this study, the rate of onset of block is slower with doxacurium while recovery is more rapid. Histamine release in three patients was caused by thiopental, while in a fourth patient it may have been due to doxacurium.

Adult↗

Neostigmine-induced prolonged neuromuscular blockade in a patient with atypical pseudocholinesterase.

A patient with unrecognized atypical pseudocholinesterase was given succinylcholine and then vecuronium before neuromuscular monitoring was instituted. Subsequently, when neostigmine and glycopyrrolate were given to reverse what was thought to be a nondepolarizing block, the patient became further relaxed, and his trachea could not be extubated for more than 10 hours. In this report, we discuss drug interactions, phase II block, and the importance of timely neuromuscular monitoring.

Butyrylcholinesterase↗

Precautions when using opioid agonists for induction of anesthesia.

Opioids produce unpredictable anesthesia that is associated with poor muscle relaxation, prolonged onset, and relatively difficult intubation. They often induce bradycardia, which must be countered with atropine or glycopyrrolate, and hypoventilation, which requires ventilatory support. Return to consciousness is often delayed, making postoperative assessment of the patient's condition difficult. Finally opioid induction is relatively expensive compared with other anesthetic induction regimens.

Anesthesia↗

Changes in serum catecholamine levels during acute bronchospasm.

STUDY OBJECTIVES: Previous studies reported that norepinephrine levels increased during acute asthma, while epinephrine levels have remained at normal levels. The purpose of this study was to determine whether the lack of rise in epinephrine levels is due to an inherent defect in catecholamine secretion in asthmatics or is a result of an insufficient stimulus for epinephrine release. DESIGN: County-owned, university-affiliated emergency department. SETTING: Prospective study. TYPE OF PARTICIPANTS: Patients more than 18 years old presenting to the ED with an acute exacerbation of asthma or chronic obstructive pulmonary disease (COPD). INTERVENTIONS: Initial phlebotomy and spirometry were followed by treatment with either albuterol or albuterol and glycopyrrolate. Asthmatic patients received steroids. Phlebotomy and spirometry were performed again after treatment. MEASUREMENTS AND MAIN RESULTS: There was no difference in epinephrine levels between patients with asthma and those with COPD either before or after treatment. Norepinephrine levels were higher in patients with COPD, both before and after treatment. There was only a weak correlation between epinephrine levels and pretreatment FEV1 for asthma but not for COPD. CONCLUSION: Moderate bronchospasm is not a major stimulus for epinephrine release in either acute asthma or COPD.

Acute Disease↗

Scopolamine enhances middle-latency auditory evoked magnetic fields.

To study the influence of central cholinergic muscarinic transmission on human cortical middle-latency auditory evoked magnetic fields (MAEF), centrally acting antagonist scopolamine hydrobromide (0.3 mg, i.v.), and peripheral muscarinic receptor antagonist glycopyrrolate (0.2 mg, i.v.), were administered to 13 healthy subjects in a double-blind randomized cross-over design. MAEF, measured with whole-head magnetoencephalography (MEG), were elicited with clicks applied at 10-Hz rate to the left ear. The amplitudes of N(b)m and P(a)m responses were augmented by scopolamine (P < 0.01 and P < 0.08). These effects were about equally strong for responses from ipsi- and contralateral auditory cortices. Thus, the present MEG findings revealed specific modulation of cortical generators of middle-latency auditory evoked responses by muscarinic transmission. These findings might be associated with auditory processing deficits observed in dementias with cholinergic disturbances.

Acetylcholine↗

Effects of tricyclic antidepressants on mechanosensitive pelvic nerve afferent fibers innervating the rat colon.

The aim of this study was to examine the effects of tricyclic antidepressants on responses of mechanosensitive afferent fibers innervating the rat colon. A total of 53 fibers in the decentralized S1 dorsal root were studied. The effects of the non-specific monoamine reuptake inhibitor imipramine (IMI), the noradrenaline reuptake inhibitor desipramine (DES), and the serotonin reuptake inhibitor clomipramine (CLO) were tested on responses of 22 mechanosensitive afferent fibers to noxious colorectal distension (CRD; 80 mmHg). Cumulative doses of 16 mg/kg of IMI, DES and of CLO reduced responses to noxious CRD to a mean 20%, 22% and 46% of control, respectively. The mean inhibitory doses of the three antidepressants did not differ significantly. Inhibitory effects were independent of potential effects on neurotransmitter reuptake: the effects of IMI and DES were not blocked by the adrenoreceptor antagonist phentolamine, and the effects of IMI and CLO were not affected by the serotonin receptor antagonist metergoline. Attenuation of afferent nerve activity was not mimicked by the anticholinergic glycopyrrolate; the cholinesterase inhibitor neostigmine did not attenuate the effect of IMI on responses to noxious CRD. Interestingly, the opioid receptor antagonist naloxone partially reversed the effects of IMI, and the NMDA receptor channel blocker MK-801 enhanced the inhibitory effects of DES and CLO. These results document that responses of mechanosensitive pelvic nerve afferent fibers to noxious CRD are significantly attenuated by tricyclic antidepressants, a peripheral action that may contribute to the beneficial effects of tricyclic antidepressants in treatment of irritable bowel syndrome.

Action Potentials↗