Susan K. Woelfel

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.

Isoflurane for refractory status epilepticus: a clinical series

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanils use as an anesthetic for children. IMPLICATIONS This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanils use as an anesthetic for children.

Effects of Bolus Administration of ORG-9426 in Children during Nitrous Oxide–Halothane Anesthesia

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)

Mivacurium chloride (BW B1090U)-induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients.

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patientsduring nitrous oxide-oxygen-isoflurane In = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supra-maximal stimulation of the ulnar nerve at 2 Hz for2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BALgroups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 ± 1.6 minutes In = 10]), than in the ISO group (7.4 ± 3.0 minutes [n = 261). The addition of isoflurane (0.5–0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade froma given dose of mivacurium and also prolongs the recovery index.

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia

&NA; We determined the dose‐response relationships of mivacurium (BW B1090U) in children (2‐10 years) during nitrous oxide‐halothane anesthesia (0.8% end‐tidal) and during nitrous oxide‐narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10‐second intervals. To estimate dose‐response relationships, for each anesthetic background four subgroups of nine patients received single bolus doses of 20‐120 μg/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log‐dose vs. probit of effect) were 52 μg/kg and 89 μg/kg during halothane anesthesia and 62 μg/kg and 103 μg/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 μg/kg mivacurium. Three of the 18 patients given 250 μg/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 μg/kg to 250 μg/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2‐4 minutes. The recovery index (T25‐75) in patients anesthetized with halothane was 4.3 ± 1.5 minute (mean ± SD); the time to complete recovery (T4:1 ≥ 0.75) was 19.8 ± 7.4 minutes.

Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide‐halothane anaesthesia

Rocuronium bromide (Zemuron) is a new steroidal nondepolarizing neuromuscular blocking drug. We were interested in determining the effect of a bolus of rocuronium in infants during halothane anaesthesia as we did previously in older children. Eighteen infants (2‐11 months) received a bolus of 600 μg·kg−1, which is equal to twice the dose of rocuronium estimated to produce 95% depression of neuromuscular function (ED95) in children (2‐12 yr). Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10‐s intervals. Time (mean ± SEM, range) from administration of 600 μg·kg−1 rocuronium to 90% (B90) and 100% (B100) neuromuscular block was 37 ± 2 (20‐60) s and 64 ± 10 (20‐180) s, respectively. The time to recovery of neuromuscular transmission to 10% (T10) was 35.3 ± 3.0 (20.7‐57.8) min and to 25% of baseline (T25) was 41.9 ± 3.2 (24.3‐67.7) min. The recovery index (T25‐T75) was 26.6 ± 2.7 (11.7‐44.5) min, and the time to recovery of the train‐of‐four ratio (T4/T1) ± 0.75 was 82.1 ± 6.9 (53.2‐138.3) min. The plasma concentration of rocuronium when T1 had recovered to about 30% was 654 ± 34 (417‐852) ng·ml−1 which is similar to that observed in children. Six‐hundred μg·kg−1 of rocuronium has a rapid onset of effect in infants and prolonged duration of action in infants compared to children.

Clinical Pharmacology of Atracurium in Infants

The neuromuscular effects of atracurium were studied in 25 infants anesthetized with 1.0% end-tidal halothane and N2O-O2. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five infants received 60, 80, and 100 μg/kg atracurium, respectively; another ten infants received 300 μg/kg (2 × ED95). The neuromuscular block produced by 60 μg/kg was 27% ± 10.9 (sem), by 80 μg/kg was 34% ± 8.0 and from 100 μg/kg was 70% ± 8.3. The ED50and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 85 μg/kg and 150 fig/kg, respectively. Neuromuscular blockade lasted 23 ± 1.6 min at 1 × ED95 and 32.5 ± 5.2 min at 2 × ED95. Changes in heart rate and mean rterial pressure were clinically insignificant.

Clinical pharmacology of doxacurium chloride (BW A938U) in children.

The neuromuscular effects of doxacurium were studied in 26 children during halothane-nitrous oxide-oxygen anesthesia. Neuromuscular blockade was measured using electromyography activity of the adductor pollicis muscle after supra maximal stimulation of the ulnar nerve at 2 Hz for 2seconds at 10-second intervals. To estimate the cumulative dose-response relation, nine patientsreceived incremental doses of doxacurium (2.5–10 μg/kg); nine patients received 27.5 μg/kg (the estimated ED95); eight patients received 50μg/kg (1.8 × ED95). The ED25, EDM, ED75′ and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 11.5, 14.8, 19.0, and 27.3 fJ-g/kg, respectively. Clinical duration (T25) was 27.8 ± 10.3 (mean ± SD) minutes at 1 × ED95 and 50.6 ± 15.6 minutes at 1.8 × ED95. Timeto recovery of the train-of-four ratio to 0.75 was 63.1 ± 32.9 minutes at 1 × ED95 and 108,5 ± 25.7 minutes at 1.8 × ED95. There were no significant changes in heart rate or mean arterial pressure after bolus administration of any dose ofdoxacurium.

Atracurium Infusion Requirements in Children during Halothane, Isoflurane, and Narcotic Anesthesia

We were interested in determining the dose---response relationship of atracurium in children (2--10 yr) during nitrous oxide---isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide---halothane (0.8%), nitrous oxide---isoflurane (1%), or nitrous oxide---narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose---response relationships, three groups of five children received 80,100, 150 μg/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 μg/kg was 23.6% ± 6.5 (mean ± SEM), by 100 μg/kg was 45% ± 7.2, and by 150 μg/kg was 64% ± 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 μg/kg and 280 μg/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 ± 0.6 μg·kg2 · min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 ± 0.8 μg·kg-1·min-1 (P < 0.05). There was no evidence of cumulation during prolonged atracurium infusion.