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Biomedical subjects

D H Bremerich

Publications and source records attributed to D H Bremerich.

At least 19 recordsLinked to original sources

[Aprotinin in cardiac surgery: more risks than usefulness?].

Antifibrinolytic therapy with the serine protease inhibitor Aprotinin or the lysine analogues epsilon-aminocapronic acid or tranexamic acid is a therapeutic measure to reduce perioperative blood loss during cardiac surgery. In an international, prospective, non-randomised phase 4 observation study, Mangano et al. investigated the effectiveness and side-effects of Aprotinin, epsilon-aminocapronic acid and tranexamic acid in comparison to no antifibrinolytic therapy in a total of 4,374 patients who underwent cardiac surgery with extracorporeal circulation. In the opinion of Mangano et al. the results of this study question the safety and effectiveness of Aprotinin for reduction of perioperative blood loss by cardiac surgery patients. Despite a critical review of the study and results reported by Mangano et al., the authors of the present paper come to the conclusion that, in view of the availability of more reasonably priced alternatives in Germany, it appears to be sensible to give preference to tranexamic acid instead of aprotinin.

Aminocaproates↗

Comparison of continuous background infusion plus demand dose and demand-only parturient-controlled epidural analgesia (PCEA) using ropivacaine combined with sufentanil for labor and delivery.

BACKGROUND: Using ropivacaine combined with sufentanil, we determined the analgesic efficacy of parturient-controlled epidural analgesia (PCEA) with or without (demand-only PCEA) continuous background infusion in reducing labor pain in 66 parturients. METHODS: After placement of the epidural catheter and administration of an initial bolus containing ropivacaine 16 mg and sufentanil 10 microg, parturients were prospectively randomized into two groups. The PCEA solution consisted of ropivacaine 0.16% plus sufentanil 0.5 microg/mL. Parturients with PCEA plus continuous background infusion received 4 mL/h plus an hourly maximum of three 4-mL boluses on demand (lock-out time 20 min); parturients with demand-only PCEA received an hourly maximum of four 4-mL boluses (lock-out time 15 min) of anesthetic solution. Pain scores (VAS 0-100 mm), drug doses administered, duration of labor, sensory and motor epidural block characteristics, maternal satisfaction, neonatal outcome and adverse events were determined. RESULTS: Both regimens provided excellent parturients' satisfaction and pain relief. However, periods of VAS scores>40 mm during all stages of labor were significantly more frequent in parturients receiving demand-only PCEA (22.4%) compared to parturients receiving PCEA plus continuous background infusion (7.5%, P=0.0011). Drug doses administered, duration of PCEA, labor and delivery, epidural block characteristics, neonatal outcome and adverse events did not differ between groups. CONCLUSION: Under the conditions of the study, PCEA plus continuous background infusion was more effective than demand-only PCEA in treating labor pain without increasing consumption of anesthetic solution.

Adult↗

[Levobupivacaine in obstetric analgesia and anaesthesia. Where is its place?].

Levobupivacaine, the S-enantiomer of racemic bupivacaine, will be available in Germany in mid-2004. Pharmacological studies demonstrated that, compared to bupivacaine, levobupivacaine has equal local anaesthetic potency with reduced potential for cardiac and CNS toxicity. This review introduces the new long-acting amide local anaesthetic levobupivacaine to the reader and evaluates its place in obstetric analgesia and anaesthesia compared to bupivacaine and ropivacaine.

Adult↗

[Anesthetic regimen for HIV positive parturients undergoing elective cesarean section].

OBJECTIVE: Worldwide, 50 million people are infected with the human immunodeficiency virus (HIV), and 43% are women. Perinatal vertical transmission of HIV accounts for most new pediatric cases. Elective Cesarean delivery, combined antiretroviral therapy perioperatively and abandonment of breast-feeding postoperatively reduces vertical HIV transmission. However, the incidence of maternal and neonatal morbidity perioperatively is relatively unknown. The goal of the present study was to prospectively record perioperative maternal and neonatal complications in the largest HIV positive collective undergoing elective Cesarean section with spinal anesthesia published to date. METHODS: From 1999-2001, 54 HIV positive parturients were enrolled in this study. All parturients received IV zidovudine therapy (2 mg/kg body weight) perioperatively. Spinal anesthesia was performed using 60 mg of 4% hyperbaric mepivacaine plus 5 microg sufentanil intrathecally. Sensory, analgesic and motor block characteristics, the incidence of maternal hypotension, postoperative maternal complications as well as neonatal outcome were recorded. RESULTS: Short-term hypotension occurred in 65% of the parturients. Intraoperatively, one parturient died following amniotic fluid embolism. In 17% of the parturients, postoperative complications headed by wound healing impairment, bronchitis and pneumonia requiring prolonged antibiotic therapy were observed. To date, after a minimum observation period of 8 months, only one infant (1.8%) is HIV positive. CONCLUSION: Intrathecal mepivacaine combined with sufentanil in HIV positive parturients undergoing elective Cesarean section is an appropriate anesthetic option. Postoperative maternal morbidity was 17%. Neonatal outcome showed no evidence of neonatal depression.

Adult↗

Mepivacaine for spinal anesthesia in parturients undergoing elective cesarean delivery: maternal and neonatal plasma concentrations and neonatal outcome.

OBJECTIVE: Worldwide, long-acting bupivacaine is most commonly used for spinal anesthesia in parturients undergoing elective Cesarean delivery. However, advances in surgical technique and shorter duration of surgery make short-acting local anesthetic like mepivacaine appropriate, particularly if combined with opioids to enhance postoperative maternal pain relief. MATERIAL AND METHODS: We assessed the effect of 4% hyperbaric mepivacaine (60 mg) plus 10 microg fentanyl for spinal anesthesia in 11 parturients undergoing elective Cesarean delivery. Sensory, motor and analgesic block characteristics, neonatal outcome (Apgar scores, umbilical cord blood analysis, neurologic and adaptive capacity score) as well as fetal and maternal mepivacaine plasma concentrations at delivery were determined (HPLC/UV). RESULTS: Motor block (Induction-Bromage 0) duration lasted 113 +/- 20 min. Effective analgesia (VAS < or = 40) was 128 +/- 35 min. Maternal and fetal mepivacaine free plasma concentration were 0.18 +/- 0.05 microg/ml and 0.10 +/- 0.03 microg/ml, respectively. The fetal to maternal (UV/MV)-ratio for mepivacaine free plasma concentration was 0.56. Apgar scores, NACScores and the umbilical blood analysis showed no evidence of neonatal depression. CONCLUSIONS: Particularly with short duration of surgery (21 +/- 5 min) intrathecal mepivacaine combined with fentanyl offers a favorable clinical alternative in parturients undergoing elective Cesarean delivery.

Anesthesia, Spinal↗

[Coronary bypass operation with complete median sternotomy in awake patients with high thoracic peridural anesthesia].

OBJECTIVE: High thoracic epidural anesthesia (TEA) combined with general anesthesia is increasingly being used for coronary artery bypass grafting (CABG) with extracorporeal circulation. Recent developments in beating heart techniques have rendered the use of TEA alone in conscious patients possible and have been reported for single-vessel beating heart CABG via lateral thoracotomy. For multi-vessel revascularization the heart is usually approached via median sternotomy, therefore the use of TEA alone was applied in awake patients with multi-vessel coronary artery disease who underwent CABG via median sternotomy. METHODS: A total of 10 patients scheduled for awake coronary artery bypass grafting (ACAB) received TEA via an epidural catheter placed at T1/2 or T2/3. Total arterial myocardial revascularization was performed after median sternotomy. In addition to standard monitoring, anesthetic sensory and motor block levels were determined using an epidural scoring scale for arm movements (ESSAM). RESULTS: Except for one patient who required intraoperative endotracheal intubation due to a pneumothorax, all patients were awake and maintained spontaneous breathing during the entire procedure. Compared to baseline values, hemodynamic parameters, e.g. arterial blood pressure (SAP, MAP, DAP) and heart rate significantly declined during coronary anastomosis. No significant hypercarbia was observed. The intraoperative pain level was subjectively estimated by the patients as less than 20 out of 100 (median 10.95% confidence interval 4.2-21.6) using a visual analogue scale. All patients rated TEA as "good" or "excellent." Adverse effects associated with TEA were not observed. CONCLUSIONS: We could demonstrate that the use of TEA alone for CABG via median sternotomy was feasible and produced good results. High patient satisfaction in our small and highly selected cohort could be reported. Nevertheless, randomized controlled trials in large cohorts are mandatory to definitively evaluate the role of TEA alone in cardiac surgery.

Aged↗

[Preoxygenation with the NasOral((R)) system or the standard face mask?].

INTRODUCTION: Adequate preoxygenation of patients before onset of apnea for orotracheal intubation is of major importance in general anaesthesia. Various preoxygenation techniques are available but a face mask providing an oxygen supply via the circle absorber system of a mechanical respirator is most frequently used. Recently, a new device for preoxygenation - the NasOral((R)) system - has become available. The aim of the present study was to compare the efficacy of intrapulmonary oxygen storage with either the NasOral((R)) device or the standard face mask. METHODS: After informed and written consent and ethics committee approval was obtained, 40 elective patients (ASA I and II) undergoing surgical procedures of the neck and mouth area, were enrolled in this randomized, prospective study. In group A ( n=20), preoxygenation was performed using the NasOral((R)) system. Patients inhaled 100% oxygen through the nose and exhaled orally through unidirectional valves. In group B ( n=20), a conventional face mask with an O(2) flow of 15 l/min and an open airway pressure release valve was used for preoxygenation. In both groups preoxygenation lasted for 2.5 min. Induction of general anaesthesia was performed in a standardized manner. After intubation patients were not ventilated until the O(2) saturation in pulse oximetry (psaO(2)) dropped to 95%. This time of apnea was recorded in both groups and we determined the hemoglobin concentration (cHb) after beginning of ventilation. RESULTS: There were no significant differences with regard to demographic data and cHb. Time of apnea leading to a O(2) saturation of 95% was 6.0+/-2.1 min in group A and 6.3+/-2.1 min in group B (mean+/-SD, p>0.05). CONCLUSIONS: Both the NasOral((R)) system and the face mask are effective for intrapulmonary oxygen storage. In both systems the O(2) flow has to be adequately high and the masks have to be held tightly in order to avoid any contamination of the inhaled oxygen with nitrogen. Due to its unidirectional flow, the NasOral((R)) system additionally requires the patient to be cooperative. As the NasOral((R)) system is more expensive and has no clinical advantages without apneic oxygenation, we prefer the standard face mask for patient preoxygenation.

Adolescent↗

[Postoperative pain therapy in pediatrics. Results of a representative survey in Germany].

The last survey addressing postoperative pain management in Germany was published in 1987, special data concerning postoperative pain management in pediatric patients had not been presented previously. The goal of this survey is to present the standard of postoperative pain management in pediatric patients in Germany. A detailed questionnaire was mailed to all German anaesthesia departments and interdisciplinary intensive care units (n = 1,500) to determine the current management of postoperative pain management in pediatric patients. After eight weeks, 42.6% of the survey had been returned. Rectally administered acetaminophen is the standard drug regimen for postoperative analgesia in children. Compared to previous surveys, the use of opioids has increased in popularity. The routine use of non-steroid antiinflammatory drugs (NSAIDs) and spasmolytics as well as the application of regional anaesthesia techniques is uncommon in pediatric postoperative pain management. Compared to other European countries, patient- or parent-controlled analgesia is more popular in Germany. Despite modern concepts of organization and a great variety of drugs available today, 71.1% of the responding anesthesiologists in this survey still believe that pediatric postoperative pain management needs to be improved.

Analgesics↗

[Fiberoptic intubation during remifentanil propofol sedation].

OBJECTIVE: Fiberoptic intubation for the management of the difficult airway is usually achieved with the patient under light sedation. The goal of the present study was to evaluate the combination of propofol and remifentanil for sedation during fiberoptic intubation. METHODS: Plans were made to use fiberoptic intubation in 40 patients with predictably difficult airways. After topical anaesthesia of the pharynx with lidocaine, oxygen was administered via nasal cannula. A capnograph was attached to determine the adequacy of ventilation and an infusion of remifentanil (0.05 microgram/kg/min) and propofol (2 mg/kg/h) was started. After the first signs of sedation, nasal fiberoptic intubation was carried out. The depth of sedation was guided by clinical observation and capnographic data and the remifentanil dose was adjusted as necessary. RESULTS: All patients, including some with very severe airway anomalies, were uneventfully intubated using the regimen we have described. Nasal capnography made it possible to monitor ventilation in all patients during bronchoscopy and intubation. The onset of hypoventilation was recognized in patients and appropriately treated by adjusting the narcotic dose. No subject became hypoxic or hypercarbic during the procedure. The changes of blood pressure and heart rate exceeded the 30% range in only one patient (a 37% blood pressure increase). Sedation was rated as good to very good in 35 patients. Coughing occurred only in 5 patients and 37 out of 40 patients had no recall that intubation had occurred. CONCLUSION: Our combination of remifentanil and propofol was shown to be a safe sedation regimen for fiberoptic intubation. Monitoring ventilation via nasal capnography and arterial oxygen saturation via pulse oximetry provided sufficient patient safety.

Adjuvants, Anesthesia↗

[Amniotic fluid embolism as an obstetric emergency--description of the syndrome and a case with fatal outcome].

Amnotic fluid embolism is an incompletely understood obstetric emergency presenting with the acute onset of hypoxia, hypotension and severe coagulopathy. Up to 86% of the cases are fatal, maternal death occurs within the first hour of symptom onset in 50% of the patients. This report describes the case of a 29-year-old, HIV-positive patient undergoing elective cesarean section who died despite immediate onset of cardiopulmonary resuscitation. The epidemiology of amniotic fluid embolism, clinical presentation, differential diagnosis, pathology and possible treatment are discussed.

Adult↗

Prophylactically-administered rectal acetaminophen does not reduce postoperative opioid requirements in infants and small children undergoing elective cleft palate repair.

UNLABELLED: Rectal acetaminophen (Ac) is often administered prophylactically at anesthesia induction for postoperative pain management in small children and is thought to have an opioid-sparing effect. We assessed in this double-blinded, prospective, randomized study early opioid requirements after three doses of Ac (10, 20, and 40 mg/kg versus placebo) in 80 children (ASA physical status I, age 11.4 +/- 9.9 mo) undergoing cleft palate repair. Single Ac plasma concentrations were measured. Pain scores assessed in the postanesthesia care unit of > or = 4 of 10 resulted in the IV administration of 25 microg/kg piritramide, a popular European mu receptor agonist (lockout time, 10 min; maximum 0.125 mg/kg). There were no significant differences between groups with regard to the early postoperative pain scores and the overall cumulative IV opioid requirements. Maximal plasma concentrations achieved were only subtherapeutic (Ac 10 mg/kg: 8 microg/mL; Ac 20 mg/kg: 13 microg/mL; Ac 40 mg/kg: 21 microg/mL after 122, 122, and 121 min, respectively). We conclude that rectal Ac up to 40 mg/kg has no opioid-sparing effect, does not result in analgesic Ac plasma concentrations, and lacks proof of its efficacy in infants and small children undergoing cleft palate repair, whereas titrated IV opioid boluses produced rapid and reliable pain relief. IMPLICATIONS: Acetaminophen is widely used prophylactically for postoperative analgesia in children and is thought to have an opioid-sparing effect. We showed that rectal acetaminophen up to 40 mg/kg administered at anesthesia induction lacked proof of efficacy, whereas IV opioid boluses resulted in reliable pain relief in children undergoing cleft palate repair.

Acetaminophen↗

[Remifentanil-propofol for bronchoscopic fiber optic intubation under capnographic control].

UNLABELLED: We report a case of a 41-years-old woman presenting for revision of a secondary reconstructive procedure using the modified Tagliacozzi upper arm flap after subtotal maxillectomy. Because of the pedicle flap the upper arm was fixed in a pre-facial position and so fiberoptic intubation was required. After routine pre-anesthetic preparations and topical anesthesia of the nares and nasopharynx a CO2 measuring catheter as well as a O2 catheter to administer 100% oxygen was inserted deeply into the left naris. At that time, a continuous infusion of 0.05 microgram/kg/min remifentanil and 2 mg/kg/h propofol was started. After 4 min, fiberoptic intubation was performed through the right nare without any technical difficulties in conscious sedation of the patient. During the entire fiberoptic intubation SaO2 was constant at 100% and capnogram tracings with etCO2 values ranging from 31 to 33 mmHg were displayed on the monitor. At the end of this second surgical procedure with fixed pre-facial upper arm position the patient was uneventfully extubated fully awake. For the time period of fiberoptic intubation the patient had complete amnesia. CONCLUSION: With the use of nasal capnography and capnometry in addition to simultaneous O2 administration during fiberoptic intubation under extreme conditions excellent analgosedation with propofol and remifentanil could be provided without compromising our patients' safety. The presented CO2 measuring and O2 administering device represents a simple and cheap expansion of standard anesthetic monitoring during fiberoptic intubation.

Adult↗

[Anesthesia in bronchial asthma].

Asthma is defined as a chronic inflammatory airway disease in response to a wide variety of provoking stimuli. Characteristic clinical symptoms of asthma are bronchial hyperreactivity, reversible airway obstruction, wheezing and dyspnea. Asthma presents a major public health problem with increasing prevalence rates and severity worldwide. Despite major advances in our understanding of the clinical management of asthmatic patients, it remains a challenging population for anesthesiologists in clinical practice. The anesthesiologist's responsibility starts with the preoperative assessment and evaluation of the pulmonary function. For patients with asthma who currently have no symptoms, the risk of perioperative respiratory complications is extremely low. Therefore, pulmonary function should be optimized preoperatively and airway obstruction should be controlled by using steroids and bronchodilators. Preoperative spirometry is a simple means of assessing presence and severity of airway obstruction as well as the degree of reversibility in response to bronchodilator therapy. An increase of 15% in FEV1 is considered clinically significant. Most asymptomatic persons with asthma can safely undergo general anesthesia with and without endotracheal intubation. Volatile anesthetics are still recommended for general anesthetic techniques. As compared to barbiturates and even ketamine, propofol is considered to be the agent of choice for induction of anesthesia in asthmatics. The use of regional anesthesia does not reduce perioperative respiratory complications in asymptomatic asthmatics, whereas it is advantageous in symptomatic patients. Pregnant asthmatic and parturients undergoing anesthesia are at increased risk, especially if regional anesthetic techniques are not suitable and prostaglandin and its derivates are administered for abortion or operative delivery. Bronchial hyperreactivity associated with asthma is an important risk factor of perioperative bronchospasm. The occurrence of this potentially life-threatening condition in anesthesia practice varies from 0.17 to 4.2%. The anesthesiologists' goal should be to minimize the risk of inciting bronchospasm and to avoid triggering stimuli. As increases in airway resistance are noticed, therapy should be directed towards optimizing oxygenation and proper diagnosis needs to be established. With deepening anesthesia level and aggressive pharmacological management utilizing both, beta-agonists and steroids, respiratory failure may be properly controlled.

Anesthesia↗

Pharmacodynamics and tolerability of acetyl starch as a new plasma volume expander in patients undergoing elective surgery.

OBJECTIVE: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase II clinical trials. We compared the pharmacodynamics and tolerability of ACS with those ofhydroxyethyl starch (HES) in 32 patients (American Society of Anesthesiologists physical status I and II) undergoing elective surgery. SUBJECTS, MATERIAL AND METHODS: In this prospective, randomized, double-blind trial patients received either 15 ml/kg ACS 6% (average molecular weight (Mw) 200,000/molar substitution (MS) 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximum dose of 1000 ml. Hemodynamic parameters, rheologic parameters, volume effect, acid-base status as well as effects on hemostasis were studied. RESULTS: After infusion of ACS and HES there was a similar increase in central venous pressure and mean arterial pressure in both groups. Acid-base status was not significantly altered after the end of the colloid infusions. After ACS infusion, plasma acetate concentration increased from 0.13+/-0.16 mg/dl to 2.87+/-1.13 mg/dl, however, after 24 h there was no significant difference in plasma acetate concentration compared to HES. The volume effect ranged from 104-116%(ACS) and from 88-118% (HES) of the colloid dose administered. These differences were not statistically significant. Partial thromboplastin time (aPTT) was only slightly increased after ACS infusion (from 38.6+/-5.7 sec to 41.4+/-5.1 sec), but was significantly increased after HES infusion (from 38.7+/-5.7 sec to 46.1+/-7.0 sec). CONCLUSION: ACS and HES are equally effective plasma volume expanders; ACS might be a new, alternative colloid solution with fewer coagulation side-effects than HES.

Adolescent↗

Carbon dioxide absorption: toxicity from sevoflurane and desflurane.

The degradation of volatile anaesthetics by desiccated carbon dioxide absorbents can result in adverse outcomes. Desiccated carbon dioxide absorbent reacting with desflurane can cause potentially life-threatening intraoperative carbon monoxide exposure; the reaction with sevoflurane can cause the formation of several toxic breakdown products, e.g. compound A. Compound A-related renal toxicity in humans is still a matter of controversy.

Journal Article↗

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery.

UNLABELLED: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. IMPLICATIONS: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.

Adolescent↗

Drug-specific effects of volatile anesthetics on Ca2+ sensitization in airway smooth muscle.

UNLABELLED: Halothane directly relaxes airway smooth muscle, partly by decreasing the Ca2+ sensitivity during membrane receptor stimulation. The effects of other volatile anesthetics on Ca2+ sensitivity are unclear. In the current study, we compared the ability of halothane, sevoflurane, and isoflurane to inhibit increases in Ca2+ sensitivity during muscarinic receptor stimulation. Beta-escin-permeabilized canine tracheal smooth muscle strips were used. Anesthetics were applied during contractions induced by 3 microM acetylcholine and 10 microM guanosine 5'-triphosphate at a constant cytosolic Ca2+ concentration of 0.3 microM. Effects were evaluated as a percent relaxation from initial force corrected for time. Halothane significantly decreased force at both low (0.76 minimum alveolar anesthetic concentration [MAC]) and high (1.8 MAC) concentrations in a concentration-dependent manner. Sevoflurane also decreased force, significantly so at a high concentration (1.7 MAC). Isoflurane did not significantly affect force even at a high concentration (1.7 MAC). Halothane's relaxing effect was significantly greater than that of the other two anesthetics at each corresponding MAC concentration. Among these three volatile anesthetics compared at equipotent anesthetic concentrations, halothane was the most potent in reducing Ca2+ sensitivity during muscarinic receptor stimulation in canine tracheal smooth muscle. This may contribute to halothane's greater relaxing effect compared with isoflurane at the same MAC concentrations in intact airway smooth muscle. IMPLICATIONS: In this study, we showed that three volatile anesthetics (halothane, sevoflurane, and isoflurane) compared at equipotent anesthetic concentrations differed in their ability to inhibit Ca2+ sensitivity during muscarinic receptor stimulation in airway smooth muscle. The potency order was halothane > sevoflurane > or = isoflurane.

Acetylcholine↗