Cisatracurium or rocuronium versus rocuronium-cisatracurium combination

The present report evaluates the incidence of pain on intravenous injection and the condition of tracheal intubation at one minute following the administration of cisatracurium or rocuronium versus rocuronium-cisatracurium combination. We studied 60 patients, ASA 1, aged 18-60 years, undergoing elective surgical procedures. The patients were randomly assigned to 3 groups who received intravenously either 0.15 mg/kg cisatracurium [2ED95], 0,6 mg rocuronium [2ED95] or a combination of 0.075 mg/kg cisatracurium [1ED95], plus 0.3 mg rocuronium [1ED95]. In the awake patients, the pain on injection of muscle relaxant was assessed on a four point scale (none, mild, moderate, severe). Administration of the relaxant was followed by 1-2 mg/kg of lidocaine and 2 mg/kg propofol. Orotracheal intubation was performed 60 seconds following the administration of the relaxant. The intubating conditions were assessed and rated as excellent, good, fair or poor. The administration of 2ED95 cisatracurium resulted in poor intubating conditions at 60s, without pain on injection. In contrast, the administration of 2ED95 rocuronium resulted in excellent or good intubating conditions at 60s associated with high incidence of pain on injection in most of the patients. However, the combination of 1ED95 cisatracurium with 1ED95 rocuronium provided similar intubating conditions to the 2ED95 rocuronium alone, associated with a significantly less pain on injection.     

Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.     

Rocuronium versus succinylcholine for rapid sequence induction of anesthesia and endotracheal intubation: a prospective, randomized trial in emergent cases

When anesthesia is induced with propofol in elective cases, endotracheal intubation conditions are not different between succinylcholine and rocuronium approximately 60 s after the injection of the neuromuscular relaxant. In the present study, we investigated whether, in emergent cases, endotracheal intubation conditions obtained at the actual moment of intubation under succinylcholine differ from those obtained 60 s after the injection of rocuronium. One-hundred-eighty adult patients requiring rapid sequence induction of anesthesia for emergent surgery received propofol (1.5 mg/kg) and either rocuronium (0.6 mg/kg; endotracheal intubation 60 s after injection) or succinylcholine (1 mg/kg; endotracheal intubation as soon as possible). The time from beginning of the induction until completion of the intubation was shorter after the administration of succinylcholine than after rocuronium (median time 95 s versus 130 s; P < 0.0001). Endotracheal intubation conditions, rated with a 9-point scale, were better after succinylcholine administration than after rocuronium (8.6 +/- 1.1 versus 8.0 +/- 1.5; P < 0.001). There was no significant difference in patients with poor intubation conditions (7 versus 12) or in patients with failed first intubation attempt (4 versus 5) between the groups. We conclude that during rapid sequence induction of anesthesia in emergent cases, succinylcholine allows for a more rapid endotracheal intubation sequence and creates superior intubation conditions compared with rocuronium.     

Comparison of the Intubation Conditions Provided by Rapacuronium (ORG 9487) or Succinylcholine in Humans during Anesthesia with Fentanyl and Propofol

Background: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation.

Methods: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography.

Results: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs.     

Dose-response and onset/offset characteristics of rapacuronium

BACKGROUND: A rigorous study of the dose-response relation of rapacuronium has, to our knowledge, yet to be performed. In addition, there is little information available regarding the onset or offset profile of rapacuronium when administered in subparalyzing doses. These issues necessitate further study. METHODS: Forty-seven adult patients, American Society Anesthesiologists physical status I or II, were studied. Tracheal intubation was accomplished without muscle relaxants. Anesthesia was maintained with use of nitrous oxide, propofol, and alfentanil. The electromyogram of the first dorsal interosseous muscle was measured using a monitor. Single stimuli at 0.10 Hz were administered. A single dose of rapacuronium was administered. After log-dose or logit transformation of the data, the best-fit line of regression was determined using the method of least squares. For each subject, the authors estimated the 50% effective dose (ED50) and 95% effective dose (ED95) from the Hill equation using the slope obtained from regression analysis. The onset times to 50 and 90% of peak effect were estimated in a subset of 10 individuals in which peak twitch depression decreased to the range of 90-99%. RESULTS: The calculated ED50 and ED95 values for rapacuronium were 0.39 +/- 0.08 (SD) and 0.75 +/- 0.16 mg/kg, respectively. After a single ED95 dose, 90% of the drug's peak effect was evident in 77 +/- 17 s. After this dose, rapacuronium has a clinical duration of 6.1 +/- 1.1 min. CONCLUSIONS: The authors found the ED95 of rapacuronium to be substantially less than suggested by previous estimates. Rapacuronium has an onset profile that is not different from that previously reported for succinylcholine. The rate of spontaneous recovery was faster after rapacuronium than the authors previously observed after mivacurium administration but was slower than after succinylcholine, using an identical protocol.     

Impact of the intubation model on the efficacy of rocuronium during rapid sequence intubation: systematic review of randomized trials

BACKGROUND: Propofol-rocuronium is thought to be superior to thiopental-rocuronium for rapid sequence intubation (RSI). The role of the intubation model per se has never been investigated. METHODS: Randomized comparisons of rocuronium with succinylcholine for true RSI (administration of muscle relaxant immediately after the hypnotic, intubation within 60 s) or modified RSI (delay between administration of the hypnotic and the muscle relaxant, intubation within 60 s) were sought. Good or excellent intubation conditions were expressed as relative risks (RR) with 95% confidence intervals (CI). RESULTS: Twelve trials (1,471 patients) used a true RSI. With propofol for induction, RR for good or excellent intubation conditions with conventional rocuronium doses (0.6-0.7 mg/kg) was 0.95 (95%CI, 0.90-1.00), with high doses (0.9-1.2 mg/kg) was 0.96 (0.92-1.01) compared with succinylcholine. With thiopental for induction, RR with conventional rocuronium doses was 0.69 (0.61-0.78) and with high doses was 0.99 (0.95-1.03). Nine trials (340 patients) used a modified RSI. With propofol for induction, RR with conventional rocuronium doses was 0.98 (0.91-1.06); data on high rocuronium doses were lacking. With thiopental for induction, RR with conventional rocuronium doses was 0.97 (0.92-1.02) and with high doses was 1.0. There was no evidence that concomitantly used opioids or the dose of the induction agent had an impact on intubation conditions, independent of the intubation model. CONCLUSION: The efficacy of rocuronium for RSI is influenced by both, the induction agent and the intubation model. To test the clinical usefulness of alternatives to succinylcholine for RSI, a true RSI model should be used.     

Dose-Response and Onset/Offset Characteristics of Rapacuronium

Background: A rigorous study of the dose-response relation of rapacuronium has, to our knowledge, yet to be performed. In addition, there is little information available regarding the onset or offset profile of rapacuronium when administered in subparalyzing doses. These issues necessitate further study.

Methods: Forty-seven adult patients, American Society Anesthesiologists physical status I or II, were studied. Tracheal intubation was accomplished without muscle relaxants. Anesthesia was maintained with use of nitrous oxide, propofol, and alfentanil. The electromyogram of the first dorsal interosseous muscle was measured using a monitor. Single stimuli at 0.10 Hz were administered. A single dose of rapacuronium was administered. After log-dose or logit transformation of the data, the best-fit line of regression was determined using the method of least squares. For each subject, the authors estimated the 50% effective dose (ED50) and 95% effective dose (ED95) from the Hill equation using the slope obtained from regression analysis. The onset times to 50 and 90% of peak effect were estimated in a subset of 10 individuals in which peak twitch depression decreased to the range of 90-99%.

Results: The calculated ED50 and ED95 values for rapacuronium were 0.39 +/- 0.08 (SD) and 0.75 +/- 0.16 mg/kg, respectively. After a single ED95 dose, 90% of the drug's peak effect was evident in 77 +/- 17 s. After this dose, rapacuronium has a clinical duration of 6.1 +/- 1.1 min.     

Use of the Intubating Laryngeal Mask Airway: Are Muscle Relaxants Necessary?

Background: The intubating laryngeal mask airway (ILMA) is designed to facilitate blind tracheal intubation. The effect of a muscle relaxant on the ability to perform tracheal intubation through the ILMA device has not been previously evaluated. This randomized, double-blind, placebo-controlled study was designed to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the success rate and incidence of complications associated with ILMA-assisted tracheal intubation.

Methods: A total of 75 healthy patients were induced with propofol 2 mg/kg and fentanyl 1 [mu]g/kg intravenously. After insertion of the ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of the study drug, tracheal intubation was attempted using a disposable polyvinyl tube. If unsuccessful, a reusable silicone tube was tried. In addition to recording the time and number of attempts required to secure the airway, the incidence of complications during placement of the tracheal tube and removal of the ILMA were noted.

Results: Tracheal intubation was successful in 76-96% of the patients. The overall success rates and times required to secure the airway were similar in all three treatment groups. The high-dose rocuronium group experienced less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than the low-dose rocuronium and saline groups, respectively. Use of rocuronium was also associated with a dose-related decrease in the requirement for supplemental bolus doses of propofol during intubation and removal of the ILMA device.     

Conditions of intubation and neuromuscular block induced by mivacurium: comparison with succinylcholine]

OBJECTIVE: To compare the clinical conditions for intubation and neuromuscular parameters after a high dose of mivacurium (0.25 mg/kg; 3 x SD95) administered in 30 s to those obtained after use of the usual dose of succinylcholine (1 mg/kg). PATIENTS AND METHODS: Eighty-two patients, 37 in the succinylcholine group and 45 in the mivacurium group, were studied. Intubating conditions were assessed on a scale of 3 to 12 points analyzing ease of laryngoscopy, relaxation of vocal cords and presence of cough 60 seconds after administration of the drug. Neuromuscular parameters were acceleration of the thumb induced by supramaximal train-of-four stimulation of the cubital nerve. Heart rate and non-invasive mean blood pressure were recorded throughout surgery. Cutaneous flush was looked for after administration of the relaxant. RESULTS: Time to onset of effect (159 s versus 82 s) and times to recovery after mivacurium were significantly longer than with succinylcholine. Mivacurium afforded excellent/good conditions for intubation in 95.6% of cases, with a neuromuscular blockade at intubation of 52.68%. No significant hemodynamic changes or side effects were observed. CONCLUSIONS: Given the moderate conditions of intubation achieved at 60 s, mivacurium can not be recommended as a relaxant in situations that require a rapid induction sequence. In elective surgery, 0.25 mg/kg of mivacurium can, however, be considered an alternative to succinylcholine.     

Use of the intubating laryngeal mask airway: are muscle relaxants necessary?

BACKGROUND: The intubating laryngeal mask airway (ILMA) is designed to facilitate blind tracheal intubation. The effect of a muscle relaxant on the ability to perform tracheal intubation through the ILMA device has not been previously evaluated. This randomized, double-blind, placebo-controlled study was designed to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the success rate and incidence of complications associated with ILMA-assisted tracheal intubation. METHODS: A total of 75 healthy patients were induced with propofol 2 mg/kg and fentanyl 1 microg/kg intravenously. After insertion of the ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of the study drug, tracheal intubation was attempted using a disposable polyvinyl tube. If unsuccessful, a reusable silicone tube was tried. In addition to recording the time and number of attempts required to secure the airway, the incidence of complications during placement of the tracheal tube and removal of the ILMA were noted. RESULTS: Tracheal intubation was successful in 76-96% of the patients. The overall success rates and times required to secure the airway were similar in all three treatment groups. The high-dose rocuronium group experienced less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than the low-dose rocuronium and saline groups, respectively. Use of rocuronium was also associated with a dose-related decrease in the requirement for supplemental bolus doses of propofol during intubation and removal of the ILMA device. CONCLUSIONS: Use of rocuronium did not significantly improve the success rate in performing tracheal intubation through the ILMA. However, it produced dose-related decreases in coughing and movement after tracheal intubation and reduced difficulties associated with removal of the ILMA device.     

Tracheal intubation conditions and cardiovascular effects after modified rapid-sequence induction with sevoflurane-rapacuronium versus propofol-rapacuronium

STUDY OBJECTIVES: To compare intubation conditions and hemodynamic effects resulting from rapid-sequence induction of anesthesia with sevoflurane-rapacuronium and propofol-rapacuronium. DESIGN: Randomized, blinded study. SETTING: Operating suites of a large university-affiliated medical center. PATIENTS: 40 ASA physical status I and II adult patients without airway abnormalities who were scheduled for elective surgery requiring endotracheal intubation. INTERVENTIONS: Patients were randomly allocated to receive either sevoflurane inhalational induction (Group 1) or propofol (2 mg/kg) intravenous induction (Group 2). Group 1 patients were coached on how to perform vital capacity breathing and the anesthesia machine was primed with sevoflurane 8%, N2O:O2 3.5:1.5 L/min. In both groups, when loss of consciousness was established, rapacuronium 1.5 mg/kg was administered. After 50 seconds, an anesthesiologist blinded to the study entered the room and attempted laryngoscopy and intubation. MEASUREMENTS: Intubation conditions were graded as excellent, good, poor, or impossible according to Good Clinical Research Practice (GCRP) criteria. Arterial blood pressure and heart rate changes accompanying both induction techniques were also monitored and recorded. MAIN RESULTS: All patients were successfully intubated within 60 seconds. Clinically acceptable intubating conditions (excellent or good scores) were obtained in 19 of 20 Group 1 patients and in 19 of 20 Group 2 patients. Moderate tachycardia was encountered in both groups and mild systolic hypotension in the Group 2 patients. There were no complications. CONCLUSIONS: Modified rapid-sequence inhalational induction using sevoflurane and rapacuronium produced clinically acceptable intubation conditions within 60 seconds of muscle relaxant administration. The intubation conditions were similar to those produced after intravenous propofol and rapacuronium.     

Probability of acceptable intubation conditions with low dose rocuronium during light sevoflurane anaesthesia in children

BACKGROUND: To define the rocuronium doses which would provide 50%, 90%, and 95% probability of 'acceptable' intubation conditions during light sevoflurane anaesthesia, we studied 60 children aged 2-7 years in a prospective, randomised, assessor blinded study. METHODS: After mask ventilation with 1 MAC sevoflurane/N2O for 17+/-1 (x+/-SD) min we administered rocuronium (either 0.15, 0.22, 0.3, 0.5, or 1.0 mg. kg(-1)) or placebo, and quantified the evoked force of the adductor pollicis muscle. Intubation conditions were assessed before and 2 min after injection of the test drug. RESULTS: Intubation conditions were improved significantly with rocuronium and scored 'acceptable' in 70%, 90%, and 100% of the children after injection of rocuronium 0.15, 0.22, and 0.3 mg x kg(-1), respectively. In parallel, twitch tension decreased to 53% (6-100), 26% (11-100), and 11% (0-19) of baseline (median (range)). Recovery of train-of-four ratio to 0.8 was achieved 13 (7-19), 16 (8-28), and 27 (23-44) min after injection of the respective rocuronium doses. Higher rocuronium doses did not further improve intubation conditions but only prolonged time of neuromuscular recovery. Logistic regression analysis revealed that rocuronium 0.11 (CI 0.05-0.16), 0.21 (0.14-0.28), and 0.25 (0.15-0.34) mg x kg(-1) provides a 50%, 90%, and 95% probability of 'acceptable' intubation conditions in children during 1 MAC sevoflurane/N2O anaesthesia, respectively. Furthermore, we calculated that force depression of adductor pollicis muscle to 81% (CI 72-90), 58% (42-74), and 50% (29-71) of baseline is associated with 50%, 90%, and 95% probability of 'acceptable' intubation conditions. CONCLUSIONS: Submaximal depression of muscle force with low dose rocuronium improves intubation conditions in children during light sevoflurane anaesthesia while allowing rapid recovery of neuromuscular function. However, when using low dose rocuronium neuromuscular monitoring may be helpful to detect children with inadequate response to the relaxant so as to avoid an unsuccessful intubation attempt.     

Circulatory responses to laryngoscopy and endotracheal intubation in patients with and without cardiovascular disease. Effect of prophylactic practolol

The effect of small intravenous doses of practolol (0.2 mg/kg body weight) on the circulatory response to laryngoscopy and endotracheal intubation, when administered with atropine (0.01 mg/kg b.w.) prior to anaesthesia was studied in 39 patients with and without cardiovascular disease. Practolol diminished significantly the rise of mean arterial pressure and pulse rate affected by laryngoscopy and endotracheal intubation when performed under thiopentone-succinylcholine anaesthesia. Arrhythmias were also less frequent through the statistical significance could not be ascertained in this small series. The small practolol dose used had no adverse circulatory effects. It is suggested that the administration of a small prophylactic dose of practolol is useful in preventing the excessive cardiovascular response due to laryngoscopy and endotracheal intubation.     

The hemodynamic effects of rapacuronium in patients with coronary artery disease: succinylcholine and vecuronium compared

Rapacuronium is a nondepolarizing muscle relaxant similar in structure to pancuronium, rocuronium, and vecuronium. Rapacuronium has a mild to moderate effect on heart rate and arterial blood pressure in ASA physical status I and II patients. However, rapacuronium was often administered after, e.g., thiopental, an inhaled anesthetic, and fentanyl, thus modifying or masking the hemodynamic effects of rapacuronium. In this study, we investigated the hemodynamic effects of rapacuronium and compared its effects with those of vecuronium and succinylcholine. Sixty patients scheduled to undergo routine coronary artery bypass grafting were selected to receive rapacuronium 1.5 mg/kg, vecuronium 0.1 mg/kg, or succinylcholine 1 mg/kg. Heart rate, blood pressure, pulmonary artery pressures, and cardiac index were measured at 30- and 60-s intervals during the 2 min after the induction of anesthesia with diazepam and for a 3-min period after study drug administration. The Rapacuronium group exhibited significantly larger decreases in blood pressure and systemic vascular resistance than the Vecuronium or Succinylcholine groups. One patient in the Rapacuronium group experienced cutaneous flushing associated with a 33% decrease in blood pressure. IMPLICATIONS: Rapacuronium is associated with a significantly larger decrease in blood pressure than succinylcholine or vecuronium, and this decrease should be considered when using rapacuronium in patients who cannot tolerate this decrease.     

A Dose-ranging Study of Rapacuronium in Pediatric Patients

Background: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children.

Methods: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 [mu]g/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph.

Results: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious.     

Does the choice of intravenous induction drug affect intubation conditions after a fast-onset neuromuscular blocker?

STUDY OBJECTIVES: To compare intubation conditions and hemodynamic effects resulting from thiopental-rapacuronium, propofol-rapacuronium, and etomidate-rapacuronium intravenous (IV) induction. DESIGN: Randomized, blinded study. SETTING: Operating suites of a large university-affiliated medical center. PATIENTS: 60 ASA physical status I and II adult patients without airway abnormalities, who were scheduled for elective surgery requiring endotracheal intubation.Patients were randomly allocated to receive IV thiopental sodium 5 mg/kg (Group 1), propofol 2 mg/kg (Group 2), or etomidate 0.3 mg/kg (Group 3) followed by rapacuronium 1.5 mg/kg. Fifty seconds later, an anesthesiologist, who had no knowledge of the induction drug used, entered the operating room and attempted laryngoscopy and intubation. MEASUREMENTS: Intubation conditions were graded as excellent, good, poor, or impossible according to Good Clinical Research Practice criteria. Arterial blood pressure and heart rate changes accompanying both induction techniques were also monitored and recorded. MAIN RESULTS: All patients were intubated within 55 to 70 seconds. Clinically acceptable intubation conditions were not statistically different among the three groups. Moderate tachycardia after induction was seen in all three groups, and blood pressure was significantly lower in Group 2 than in Groups 1 or 3. CONCLUSIONS: Clinically acceptable intubation conditions are similar after either thiopental, propofol, or etomidate when a fast-onset neuromuscular blocking drug (rapacuronium 1.5 mg/kg) is used to facilitate tracheal intubation.     

A dose-ranging study of rapacuronium in pediatric patients

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.     

复合七氟烷吸入用于患儿无肌松药气管插管时瑞芬太尼的半数有效剂量

目的 确定复合七氟烷吸入用于患儿无肌松药气管插管时瑞芬太尼的半数有效剂量(ED50).方法 择期手术患儿25例,年龄4～9岁,ASA Ⅰ或Ⅱ级.吸入5%七氟烷行麻醉诱导,维持呼气末二氧化碳分压30～35 mm Hg.吸入七氟烷3 min后静脉注射瑞芬太尼,注射时间30 s,瑞芬太尼注射完毕后90 s时行气管插管.采用序贯法进行试验,瑞芬太尼初始剂量为1.2 μg/kg,相邻剂量比值为1.2.采用Viby-Mogensen评分法评价气管插管条件,气管插管失败时,静脉注射罗库溴铵0.3 mg/kg,待肌肉松驰后再行气管插管.计算瑞芬太尼的ED50及其95%可信区间.结果 复合5%七氟烷吸入用于患儿无肌松药气管插管时瑞芬太尼的ED50及其95%可信区间为0.68(0.65～0.71)μg/kg.结论 复合5%七氟烷吸入用于患儿无肌松药气管插管时瑞芬太尼的ED50及其95%可信区间为0.68(0.65～0.71)μg/kg.     

Intubationsbedingungen und Verlauf der neuromuskulären Blockade nach Rocuronium bei endoskopischen Operationen in der HNO-Heilkunde

Rocuronium is a new nondepolarizing muscle relaxant for which a fast onset has been described. The goal of this study was to examine whether the characteristics of rocuronium could make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. These operations, which require the anaesthesiologist and surgeon to ”share” the patient’s airway, require good muscle relaxation for endotracheal intubation and placement of endoscopic instruments. In addition, the time course of neuromuscular blockade and its relation to the quality of intubating conditions were analysed. Methods: The study was approved by the local ethics committee; 30 patients (ASA status 1–3) scheduled for elective endoscopic upper airway surgery were included after written informed consent. Exclusion criteria were suspected difficult intubating conditions, neuromuscular disease, or antibiotic therapy with aminoglycosides during the last 24?h. Anaesthesia was induced by propofol 2?mg/kg and alfentanil 1?mg after volume loading with 500?ml Ringer’s lactate and preoxygenation, and was maintained by propofol infusion 5–8?mg/kg/h and repetitive alfentanil injections according to clinical needs. Endotracheal intubation was performed by a senior anaesthesiologist 90?s after injection of rocuronium 0.6?mg/kg (2×ED₉₅). Intubating conditions were graded 1 to 4 (1=excellent, 2=good, 3=sufficient, 4=inadequate). Acceleromyography was used for neuromuscular monitoring by means of the TOF-guard (Organon Teknika/Biometer). The adduction movement of the thumb was measured by an acceleration transducer while stimulating the ulnar nerve at the wrist via surface electrodes in a supramaximal train-of-four (TOF) mode (2?Hz every 15?s). Twitch height and TOF ratio were documented during the course of neuromuscular blockade. Data are presented as mean±standard deviation. Results: Patients were aged 37 to 64 years (mean 54±7). Intubating conditions were excellent in 17 cases and good in 7. In 2 cases intubating conditions were graded sufficient, as patients could be easily intubated but showed clear diaphragmatic movements at intubation. In 4 patients intubating conditions could not be judged, as a laryngoscopic view of the glottic structures was impossible for anatomic reasons. Neuromuscular block at intubation was 78±22%, onset time 152±62?s, clinical duration 30±8?min, and recovery index 11±4?min. The TOF ratio required 51±14?min to return to 0.7. Conclusions: Good to excellent intubating conditions can be expected 90?s after injection of rocuronium 0.6?mg/kg. Diaphragmatic reactions cannot be excluded. Complete relaxation of the adductor pollicis muscle is not necessary for endotracheal intubation. Intubation at a certain time interval, for example, 90?s after injection of rocuronium 0.6?mg/kg, can be recommended. Onset and recovery characteristics of rocuronium make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. Care should be given, however, to detect inadequate recovery of neuromuscular transmission, as there are considerable interindividual differences in recovery.     

Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration

BACKGROUND: A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. METHODS: Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. RESULTS: Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. CONCLUSIONS: In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.