Etsuro K. Motoyama

Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane.

Background Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open‐labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed. Methods Three hundred seventy‐five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurane or halothane, both in 60% N2 O and 40% O2. Anesthesia was induced using a mask with an Ayres t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End‐tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia. Results During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC *symbol* h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end‐tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean (+/‐SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3+/‐3.5 micro Meter. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004). Conclusions Sevoflurane compared favorably with halothane. Early recovery after sevoflurane was predictably more rapid than after halothane, although this was not reflected in a more rapid discharge from the hospital. The incidence of adverse events was similar for both anesthetics. Clinically, the induction, recovery, and safety characteristics of sevoflurane and halothane are similar. Sevoflurane is a suitable alternative to halothane for use in children undergoing minor ambulatory surgery.

Clinical Characteristics of Sevoflurane in Children A Comparison with Halothane

Background For pediatric patients, sevoflurane may be an alternative to halothane, the anesthetic agent used most commonly for inhalational induction. The induction, maintenance, and emergence characteristics were studied in 120 unpremedicated children 1–12 yr of age randomly assigned to receive one of three anesthesia regimens: sevoflurane with oxygen (group S), sevoflurane with nitrous oxide and oxygen (group SN), or halothane with nitrous oxide and oxygen (group HN). Methods Anesthetic was administered (via a Mapleson D, F or Bain circuit) beginning with face mask application in incremental doses to deliver maximum inspired concentrations of 4.5% halothane or 7% sevoflurane. End‐tidal concentrations of anesthetic agents and vocal cord position were noted at the time of intubation. Elapsed time intervals from face mask application to loss of the eyelash reflex, intubation, surgical incision, and discontinuation of the anesthetic were measured. Heart rate, systolic, diastolic, and mean blood pressures, and end‐tidal anesthetic concentrations were measured at fixed intervals. Anesthetic MAC‐hour durations were calculated. The end‐tidal concentration of anesthetic was adjusted to 1 MAC (0.9% halothane, 2.5% sevoflurane) for at least the last 10 min of surgery. Intervals from discontinuation of anesthetic to hip flexion or bucking, extubation, administration of first postoperative analgesic, and attaining discharge criteria from recovery room were measured. Venous blood was sampled at anesthetic induction, at the end of anesthesia, and 1, 4, 6, 12, and 18–24 h after discontinuation of the anesthetic for determination of plasma inorganic fluoride content. Results Induction of anesthesia was satisfactory in groups SN and HN. Induction in group S was associated with a significantly greater incidence of excitement (35%) than in the other groups (5%), resulting in a longer time to intubation. The end‐tidal minimum alveolar concentration multiple of potent inhalational anesthetic at the time of intubation was significantly greater in patients receiving halothane than in patients receiving sevoflurane. Induction time, vocal cord position at intubation, time to incision, duration of anesthesia, and MAC‐hour duration were similar in the three groups. During emergence, the time to hip flexion was similar among the three groups, whereas the time to extubation, time to first analgesic, and time to attaining discharge criteria were significantly greater in group HN than in groups S and SN. Mean heart rate and systolic blood pressure decreased during induction in group HN but not in groups S and SN. The maximum serum fluoride concentration among all patients was 28 micro Meter. Conclusions Sevoflurane with nitrous oxide provides satisfactory anesthetic induction and intubating conditions; however, induction using sevoflurane without nitrous oxide is associated with a high incidence of patient excitement and prolonged time to intubation. There were greater decreases in heart rate and systolic blood pressure during induction with halothane than with sevoflurane; however, these differences may be dose‐related. The more rapid emergence with sevoflurane when compared with halothane is consistent with the low solubility of sevoflurane in blood and tissues. Children receiving sevoflurane for up to 9.6 MAC‐hours did not develop high serum fluoride concentrations.

Pulmonary Aspiration in Pediatric Patients During General Anesthesia: Incidence and Outcome

STUDY OBJECTIVES To determine the incidence of, outcome of, and risk factors for anesthesia-related pulmonary aspiration in the predominantly pediatric population receiving anesthesia care. DESIGN Using a clinical concurrent quality assessment system we developed, we used data stored in a custom-designed computerized database to initiate a retrospective review. Statistical relationships were analyzed by Fishers exact test and binary logistic regression with commercially available software. SETTING University-affiliated pediatric hospital. PATIENTS All patients receiving anesthesia (n = 50,880) between April 1, 1988, and March 31, 1993. MEASUREMENTS AND MAIN RESULTS Aspiration occurred in 52 (0.10% or 10.2 per 10,000) of the 50,880 general anesthesia cases. Aspirate was food or gastric contents in 25 cases (0.049% or 4.9 per 10,000), blood in 13 (0.026% or 2.6 per 10,000), and unknown material in 14 (0.0275% or 2.76 per 10,000). There were no deaths attributable to aspiration. Morbidity was confined to unanticipated hospital admission (n = 12), cancellation of the surgical procedure (n = 4), and intubation, with or without ventilation (n = 15). Aspiration occurred significantly more often in patients with greater severity of underlying illness (ASA physical status III or IV) (p = 0.0015), intravenous induction (p = 0.0054), and age equal to or greater than 6.0 years and less than 11.0 years (p = 0.0029). Emergency procedures had a marginally significant increased aspiration risk (p = 0.0527). CONCLUSIONS The overall incidence of anesthesia-related aspiration in our series (0.10%) was twice that reported in studies of adults, and four times (0.25%) higher for those at highest risk (ASA physical status III or IV vs. physical status I or II). Anesthesia-related pulmonary aspiration was proven to be a rare event in this tertiary pediatric center and its consequences relatively mild. Because of the very low frequency and the lack of serious outcome after aspiration in ASA physical status I and II pediatric patients, it appears that routine prophylactic administration of histamine blockers or propulsive drugs in healthy pediatric patients is unwarranted.

Multicenter Study of General Anesthesia. II. Results

A prospective, stratified, randomized clinical trial of the safety and efficacy of four general anesthetic agents (enflurane, fentanyl, halothane, and isoflurane) was conducted in 17,201 patients (study population). Patients were studied before, during, and after anesthesia for up to 7 days. Nineteen patients died (0.11%), and in seven of these (0.04%) the anesthetic may have been a contributing factor. The rates of death, myocardial infarction, and stroke in the study population were so low (less than 0.15%) that no conclusions regarding the relative rates of these outcomes among the four anesthetic agents could be reached. The rates of 16 of 66 types of adverse outcomes in the study population were significantly different among the four study agents. Most of these outcomes were minor. However, severe ventricular arrhythmia (P less than 10(-6)) was more common with halothane, severe hypertension (P less than 10(-6)) and severe bronchospasm (P = 0.028) were more common with fentanyl, and severe tachycardia (P = 0.001) was more common with isoflurane. Recovery from anesthesia during the first 30 min was slowest in those patients who received halothane (P less than or equal to 0.001). In addition, patients who received fentanyl experienced less pain during the first hour in the recovery room (P less than 10(-6)). In conclusion, clinically important differences do exist for some outcomes among the four study agents.

Continuous Monitoring of Arterial Oxygen Saturation with Pulse Oximetry during Transfer to the Recovery Room

The incidence of hypoxemia in the immediate postoperative period was determined using a pulse oximeter for continuous monitoring of arterial oxygen saturation (Sao2) in 95 ASA class I or II adult patients breathing room air during their transfer from the operating room to the recovery room. Hypoxemia was defined as 90% Sao2 (arterial oxygen partial pressure (PaO2) ≅ 58 mm Hg). Severe hypoxemia was defined as 85% Sao2 (PaO2 ≅ 50 mm Hg). Hypoxemia occurred in 33 (35%) patients; severe hypoxemia occurred in 11 (12%). Postoperative hypoxemia did not correlate significantly with anesthetic agent, age, duration of anesthesia, or level of consciousness. There was a statistically significant correlation (P < 0.05) between hypoxemia and obesity. All three patients with a history of mild asthma became severely hypoxemic even though none had perioperative evidence of obstructive disease, also a statistically significant (P < 0.003) finding.

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow‐volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air‐trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV1), and the ratio FEV1/FVC remained at or above the predicted normal range in all patients. FEF25–75, FEF50, and FEF75 were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air‐trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34.

Effect of preoperative stabilization on respiratory system compliance and outcome in newborn infants with congenital diaphragmatic hernia.

To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.

Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals, and diaphragm in cats: an electromyographic study

To determine the possible differential effects of depth of inhalation anesthetics on inspiratory muscle activity, the following were studied in seven adult cats: the phasic activity of the diaphragm, the external intercostals, and the genioglossus, by means of electromyography (EMG) and its moving time average (MTA). The animals spontaneously breathed 1.0-3.0% halothane in O2, while arterial PCO2 was maintained constant at approximately 60 mmHg by adjusting CO2 in the inspired gas mixture. Muscle activity was evaluated in terms of peak height of MTA, with measurements at 1% halothane used as control values. Halothane anesthesia attenuated inspiratory muscle activity significantly (P less than 0.05) in a dose-dependent fashion; muscle activity decreased most in the genioglossus, least in the diaphragm, and intermediately in the intercostals. Respiratory frequency, inspiratory time, and inspiratory duty cycle did not change significantly with increasing concentration of halothane.

Cardiac output during liquid (perfluorocarbon) breathing in newborn piglets

Background and MethodsLiquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (&OV0422;t) in several animal species, casting doubt as to its feasibility. This study tested whether &OV0422;t could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous &OV0422;t measurement, and subjected to 2 hr of liquid breathing. Paco2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and Pao2 >80 torr (>10.7 kPa). Additional colloid was given during liquid breathing if &OV0422;t decreased to <90% of preliquid breathing values. ResultsFour piglets maintained &OV0422;t throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for &OV0422;t 82% to 89% of the baseline value, after which &OV0422;t rapidly increased to >90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing. Conclusion&OV0422;t is readily maintained during liquid breathing in properly hydrated animals. (Crit Care Med 1991; 19:225)

Effects on lung function of multiple expansion thoracoplasty in children with thoracic insufficiency syndrome: a longitudinal study.

Study Design. Longitudinal study of intraoperative pulmonary function in young children with thoracic hypoplasia and scoliosis undergoing multiple expansion thoracoplasty using the vertical expandable prosthetic titanium ribs (VEPTRs). Objective. To test the long-term efficacy of VEPTR multiple expansion thoracoplasty. Summary of Background Data. To our knowledge, no direct measurements of pulmonary function have been reported with VEPTR expansion thoracoplasty. Methods. There were 10 children with thoracic insufficiency syndrome, secondary to thoracic hypoplasia with progressive scoliosis, studied. A mobile pulmonary function laboratory unit was used to study forced vital capacity (FVC), maximum expiratory flow volume curves, and respiratory system compliance (Crs) with the patient under general anesthesia immediately before and after expansion thoracoplasty. Studies were repeated every 6 months at each subsequent operation for expansion thoracoplasty for the duration up to 33 months. Results. At the baseline studies, FVC showed a moderate-to-severe decrease (69% of predicted values), indicating the presence of significant restrictive lung defect. Only 1 of 10 children had severe airway obstruction. The baseline Crs was markedly decreased in part because of the presence of significant atelectasis. Crs increased with an average of 42% after repeated hyperinflation (deep sighs). There was no change in lung volume or function immediately before versus after completion of expansion thoracoplasty. FVC increased significantly over time, with an average rate of 26.8% per year, the rate of increase similar to that of healthy children of comparative ages. In terms of percent-predicted values, FVC did not change significantly between the baseline and last test, indicating that in most children studied, lung growth kept up with body growth. Conclusion. Although it is difficult to assess the extent of the efficacy without a proper or historical control group for comparison, the present study indicates that in children with severe thoracic insufficiency syndrome, the insertion of VEPTRs with multiple expansion thoracoplasties is beneficial over time, by allowing the lungs to expand with body growth without further deterioration in lung function.