Lai K. Luo

Dose-response and time course of effect of rocuronium in male and female anesthetized patients

To determine differences from dose-response and time-course of rocuronium between male and female patients, 60 adult patients (30 male and 30 female), ASA grade I, aged 17-52 yr, undergoing elective plastic surgery were studied. Anesthesia was maintained with 60% nitrous oxide in oxygen, thiopental, and incremental doses of fentanyl as required. Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 s, and the percentage depression of the T1 response was used as the study variable. The dose-response relationship of rocuronium was determined by a cumulative dose-response technique. The results showed that the dose-response curve of rocuronium in the men was shifted to the right, indicating a decrease in the sensitivity to rocuronium-induced neuromuscular block versus the women. The 50%, 90%, and 95% effective doses of rocuronium were 178.4 +/- 53.7, 358.7 +/- 101.3, and 386.2 +/- 113.4 micro g/kg, respectively, in male patients, and 128.8 +/- 42.5, 252.8 +/- 51.7, and 274.4 +/- 59.4 micro g/kg in female patients. After an intravenous administration of total dose of 400 micro g/kg rocuronium, neuromuscular block was significantly longer in the men than in the women. The duration of peak effect, clinical duration, and total duration were 6.5 +/- 3.0,12.5 +/- 4.9, and 33.6 +/- 8.7 min, respectively, in male patients, and 11.8 +/- 2.7, 18.5 +/- 5.3, and 46.8 +/- 9.6 min in female patients. We conclude that women were approximately 30% more sensitive to rocuronium compared with men. Implications: The authors found that women were 30% more sensitive to rocuronium than men. This suggests that the routine dose of rocuronium should be reduced in women compared with men. (Anesth Analg 1997;85:667-71)

The influence of surgical sites on early postoperative hypoxemia in adults undergoing elective surgery.

UNLABELLED To determine the influence of the surgical sites on early postoperative hypoxemia, we studied postoperative hypoxemia in 994 patients, ASA physical status I or II, aged 18-68 yr, scheduled for various types of elective surgery. Patients were divided into three groups on the basis of the surgical sites: Group 1 = elective superficial plastic surgery (n = 288); Group 2 = upper abdominal surgery (n = 452); and Group 3 = thoracoabdominal surgery (n = 254). Anesthesia was maintained with 1%-2% enflurane and 67% nitrous oxide in oxygen; thiopental or fentanyl was given IV as required. SpO2 levels were recorded while patients breathed room air shortly after arrival in the recovery room (0 min) and 5, 10, 15, 20, 30, 40, 50, 60, 120, and 180 min thereafter. The results showed that during the early postoperative period, the degree of arterial desaturation and the incidences of hypoxemia (SpO2 86%-90%) and severe hypoxemia (SpO2 85%) were closely related to the operative sites and were greatest for thoracoabdominal operations, less for the upper abdominal operation, and least for the peripheral surgery. The incidence of hypoxemia and severe hypoxemia in the recovery room was 7% and 0.7%, respectively, in Group 1, 38% and 3% in Group 2, and 52% and 20% in Group 3. Mild airway obstruction and hypothermia in the postanesthesia recovery unit (PAR) were the predictive factors of early postoperative hypoxemia. We conclude that during the early postoperative period, there were significant differences in SpO2 levels and incidences of hypoxemia and severe hypoxemia among the three groups. IMPLICATIONS We found that the severity of arterial desaturation and the incidence of hypoxemia during the early postoperative period are closely related to the surgical sites and are strongest for thoracoabdominal surgery, less for upper abdominal surgery, and least for peripheral surgery.

The pharmacokinetics of vecuronium in male and female patients

To evaluate the effect of gender on the pharmacokinetics of vecuronium, we studied 30 patients (15 male and 15 female) undergoing elective plastic surgery with anticipated surgical blood loss of <300 mL under general anesthesia.General anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 [micro sign]g/kg and was maintained with 60% nitrous oxide in oxygen and an end-tidal concentration of 1.5%-2% enflurane. After a 2-min infusion of vecuronium 100 [micro sign]g/kg, a modified fluorometric assay was used to determine the plasma concentrations of vecuronium for 5 h. The results showed that, compared with women, the plasma concentrations of vecuronium in men were significantly lower during the first 20 min and that the disposition kinetics of vecuronium can be best described mathematically by a three-compartment open model in the two groups. The volume of the central compartment and the volume of distribution at steady state were 39.6 +/- 8.6 and 164.8 +/- 29.3 mL/kg, respectively, in women. These values increased significantly to 54.4 +/- 14.4 and 201.4 +/- 75.8 mL/kg in men (P < 0.05). When the data were calculated on the basis of ideal body weight, the volume of distribution of vecuronium was also different between men and women (P < 0.05. The half-lives of fast distribution and distribution, the elimination half-life, mean residual time, area under the plasma-concentration curve, and plasma clearance were not different between the two groups. We conclude that the pharmacokinetics of vecuronium are significantly different between genders and that and men have the greater volume of distribution of vecuronium. Implications: The authors found that, compared with women, men had lower plasma concentrations of vecuronium after the IV administration of vecuronium and a larger volume of distribution of vecuronium. The pharmacokinetic differences may be related to the differences in the sensitivity to vecuronium between genders. (Anesth Analg 1998;86:1322-7)

Study of the safe threshold of apneic period in children during anesthesia induction

STUDY OBJECTIVES (1) To investigate changes in arterial oxygen saturation via pulse oximeter (SpO2) during apnea and after reinstitution of manual ventilation at SpO2 of 95% or 90% following rapid sequence induction of anesthesia in children after 2-minute preoxygenation; (2) to determine whether the setting of a safe threshold of apneic period to an SpO2 of 95% is appropriate in children during anesthetic induction; and (3) to evaluate the influences of age, body weight, and height on the time from the start of apnea to SpO2 of 95%. DESIGN A clinical study of random design and comparison among groups. SETTING Operating room of a plastic surgery hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS 152 infants and children, ASA physical status 1, aged 3 months to 12 years, scheduled for elective plastic surgery. INTERVENTIONS Patients were divided into three age groups: Group 1-infants 3 months to 1 year (n = 39); Group 2 children 1 to 3 years (n = 41); and Group 3-children 3 to 12 years (n = 72). Patients in each age group were randomly allocated again to Subgroups A and B. After a 2-minute preoxygenation, anesthesia was induced with thiopental 5 mg/kg, fentanyl 5 micrograms/kg and suxamethonium 1.5 mg/kg. Patients were manually ventilated when SpO2 decreased to 90% in Subgroups A and 95% in Subgroups B, respectively, during apnea. MEASUREMENTS AND MAIN RESULTS SpO2 was measured continuously with a Datex pulse oximeter applied to the right index finger. During apnea, the times for SpO2 to decrease to 09% (T99) and 95% (T99) in all children, and 90% (T90) in Subgroups A were recorded. The time for SpO2 to decrease from 95% to 90% (T95-90) in Subgroups A was also measured. After reinstitution of manual ventilation, the time when SpO2 continued to decrease (T1) and the time from the end of apnea to recovery of SpO2 baseline (T2) were determined. In addition, the lowest value of SpO2 after apnea was also recorded. The results showed that younger children were more susceptible than older children to the risk of hypoxemia during apnea. There were significant differences in T99, T95, T90, and T95-90 between the three age groups T1 and T2 were significantly longer in Group 3 than in Groups 1 and 2. There were significant differences in the lowest values of SpO2 following apnea among the three Subgroups A and between Subgroups A and B of each age group. During apnea, heart rate decreased gradually as SpO2 decreased, showing a significant decrease at SpO2 of 95%. Bradycardia was found in three children in Subgroups A. The apnea time to SpO2 of 95% correlated well with age, weight, and height by linear regression analysis. CONCLUSIONS The safe threshold of an apneic period setting to an SpO2 of 95% was appropriate in children during anesthesia induction. Despite the same duration of preoxygenation, younger children were more susceptible than elder ones to the risk of hypoxemia during apnea. The apnea time to SpO2 of 95% correlated with age, body weight, and height using linear regression analysis.

Dose–response and time‐course of the effect of rocuronium bromide during sevoflurane anaesthesia

To evaluate the influence of sevoflurane on the dose–response relationship and on the time‐course of the effect of rocuronium, 60 adult patients undergoing elective plastic surgery were randomly allocated to either the control or the sevoflurane group. Anaesthesia was maintained with 60% nitrous oxide in oxygen and thiopentone in the control group and with 60% nitrous oxide in oxygen and an end‐tidal concentration of 1.75% sevoflurane in the sevoflurane group. Neuromuscular function was assessed mechanomyographically with train‐of‐four stimulation at the wrist every 12 s and the percentage depression of the first twitch of the train‐of‐four was used as the study parameter. The dose–response relationship of rocuronium in the two groups was determined by the cumulative dose–response technique. The dose–response curve of rocuronium in the sevoflurane group was shifted to the left compared to the control group, indicating a potentiation of rocuronium‐induced neuromuscular block. The effective doses of rocuronium required to produce 50%, 90% and 95% twitch depression in the sevoflurane group were decreased by 30.5%, 26.7% and 25.2%, respectively, compared to the control group. Following the administration of a total dose of rocuronium of 400 μgkg−1, the duration of action of, and the recovery from, rocuronium were both significantly prolonged by sevoflurane. There were significant differences in the duration of peak effect, clinical duration, recovery index and the total duration of action between the control and the sevoflurane groups.

Observation of early postoperative hypoxaemia in children undergoing elective plastic surgery

The incidence, severity and duration of early postoperative hypoxaemia were determined in 420 healthy infants and children undergoing elective plastic surgery. Mean value of preoperative Spo2 was 98.3 ± 0.87%. However, it decreased significantly to 92.7 ± 4.01% immediately following anaesthesia in the postanaesthesia recovery room (PAR) when children breathed room air. Then Spo2 gradually increased to 93.8 ± 4.25% at 10 min, 95.4 ± 3.14% at 30 min, 96.6 ± 2.25% at 60 min, 96.9 ± 1.69% at 120 min, and 97.4 ± 1.55% at 180 min, respectively. The incidence of hypoxaemia and severe hypoxaemia, which were 14.8% and 6.2% respectively on arrival in the PAR, decreased significantly to 6.6% and 1.9%, 30 min later. The hypoxaemia occurred most commonly within 1 h, particularly the first 30 min following anaesthesia. The hypoxaemia was more common and more severe in children undergoing cleft palate repair than other kinds of plastic surgery. A significant correlation was found between low Spo2 levels on admission to the PAR and childrens age, fentanyl doses, and the infants’ recovery score.

Influence of acute normovolaemic haemodilution on the dose-response and time-course of action of atracurium.

Background: Acute normovolaemic haemodilution is a common method to save and avoid homologous blood transfusion during surgery. The aim of this study was to evaluate the influence of acute isovolaemic haemodilution on the dose‐response and time‐course of action of atracurium.

The influence of acute normovolemic hemodilution on the dose-response and time course of action of vecuronium

To evaluate the influence of acute isovolemic hemodilution on the dose-response and time course of action of vecuronium, we studied 60 adult patients with and without hemodilution during surgery. The patients with hemodilution underwent major elective plastic surgery with an anticipated surgical loss of more than 600 mL. Anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 [micro sign]g/kg IV and was maintained with 60% nitrous oxide in oxygen. Further increments of thiopental 2 mg/kg or fentanyl 2 [micro sign]g/kg were given as required. Acute isovolemic hemodilution in the hemodilution group was induced by drainage of venous blood and an IV infusion of lactated Ringers solution and 6% dextran, during which hematocrit and hemoglobin decreased from 45.7% to 26.2% and from 148.5 g/L to 90.2 g/L, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s, and the percent depression of T1 response was used as the study parameter. The dose-response relationships of vecuronium in the two groups were determined by using the cumulative dose-response technique. The results showed that during hemodilution, the dose-response curve of vecuronium was shifted to the left in a parallel fashion, and the potency of vecuronium was increased. There were significant differences in the 50%, 90%, and 95% effective doses between the two groups. After the IV administration of vecuronium 80 [micro sign]g/kg, vecuronium-induced neuromuscular block was significantly longer in the patients with hemodilution than in the control patients. The duration of peak effect, clinical duration, recovery index, and total duration in the hemodilution patients were significantly different from those in the control patients. We conclude that hemodilution induces significant changes in the pharmacodynamics of vecuronium. Implications: We found that patients with hemodilution were 20% more sensitive to vecuronium and had a longer duration of action after the administration of the same dose than the controls. This should be taken into account when vecuronium is used as a muscle relaxant during acute hemodilution. (Anesth Analg 1998;86:861-6)

A comparative study of the dose-response and time course of action of rocuronium and vecuronium in anesthetized adult patients

STUDY OBJECTIVES (1) To compare the dose-response relations of rocuronium and vecuronium in healthy adult patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental; and (2) to evaluate the time-course of action of two drugs following equipotent doses. DESIGN Prospective, randomized, clinical comparison. SETTING Operating room, Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS 60 ASA physical status I patients, aged 17-51 years, scheduled for elective plastic surgery. INTERVENTIONS All patients were randomly assigned to either the rocuronium or vecuronium group. General anesthesia was induced with thiopental 4 to 6 mg/kg and fentanyl 2 to 4 micrograms/kg intravenously (i.v.), and maintained with 60% nitrous oxide (N2O) in oxygen. Further increments of thiopental or fentanyl were given as required. The dose-response relations of rocuronium and vecuronium were determined by the cumulative dose-response technique. MEASUREMENTS AND MAIN RESULTS Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of first twitch (T1) was used as the study parameter. The cumulative dose-response curve of vecuronium was shifted to the left in a parallel fashion compared with that of rocuronium. As assessed by linear regression, the potency ratio of vecuronium: rocuronium was 1:7.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After i.v. administration of equipotent doses of both drugs (2 x ED90), the duration of peak effect, clinical duration, recovery index, and total duration were not significantly different between the two drugs. CONCLUSIONS Compared with vecuronium, rocuronium is a low-potency, nondepolarizing relaxant, and its neuromuscular blocking potency is approximately 15% that of vecuronium in adult patients anesthetized with N2O and fentanyl. Following equipotent doses, the time-course of recovery for rocuronium is similar to that of vecuronium.

Observation of the correlation of postanaesthesia recovery scores with early postoperative hypoxaemia in children

To observe the correlation of the postanaesthesia recovery score (PARS) with the incidence, and severity of early postoperative hypoxaemia in children, 1213 infants and children, ASA physical status I, aged three months to 14 years, scheduled for elective plastic surgery were included in this study. Arterial oxygen saturation (SpO 2) levels were recorded while children were breathing room air shortly after arrival in the recovery room (0 min), and 5, 10, 15, 20, 30, 40, 50, 60, 120 and 180 min thereafter. The PARS was also determined on all patients when SpO 2 levels were recorded in the recovery room. On the basis of different PARS, children were divided into the three groups: Group 1 – children having the PARS of ≤6; Group 2 – children having the PARS of 7–9; and Group 3 – children having a PARS of 10. The results showed that during the early postoperative period, the incidence and severity of hypoxaemia correlated closely with the PARS. The lower the childrens PARS, the higher the incidences of hypoxaemia (SpO 2=86–90%) and severe hypoxaemia (SpO 2≤85%). The incidences of hypoxaemia and severe hypoxaemia were 12.9% and 15.8%, respectively, in Group 1, 20.9% and 2.9% in Group 2, 0.8% and 0% in Group 3. There were significant differences among the three groups. Of the 91 children who required O2 supplementation in the recovery room because of low measured SpO 2, 69 had the PARS of ≤6, and 22 had the PARS of 7–8. It is concluded that if a patient has a PARS of 10, the patient will not need routine oxygen supplement because hypoxaemia will not occur.