Within 48 hours of discharge from the hospital, the parents were contacted by telephone by the research nurse to complete a structured questionnaire that included postoperative complications, all other problems, and the parent’s overall satisfaction with the anesthetic.
Sample size was estimated a priori using the following assumptions based on our clinical experience of adverse airway events with both techniques and the available literature16–18: α2 0.05, β 0.2, a 30% incidence of adverse airway events in the children anesthetized with isoflurane/N2O,16 and a 10% incidence in those anesthetized with propofol.17,18 These assumptions yielded a sample size of 72 children in each group. To account for study failures and dropouts, 75 children were enrolled in each group.
The primary outcome variable, the frequency of adverse airway events, was compared using Fisher exact test and reported as the 95% confidence interval of the risk difference using Instat 3.0b, 2003 (GraphPad, La Jolla, CA). Secondary outcome variables including cardiorespiratory responses were compared using 2-way repeated measures MANOVA (multivariate analysis of variance) with group (propofol and isoflurane) as the between-subjects factors and time (0–25 minutes) as the repeated measures factor. To control for experiment-wise errors, post hoc pairwise between group comparisons for systolic blood pressure, heart rate, ETCO2, and respiratory rate were compared using the t test and reported as Bonferroni-adjusted P values, 0.0083. Normally distributed demographic data (i.e., age, weight) were analyzed for between-group differences using unpaired Student t test. Nominal data (i.e., sex) were analyzed using χ2 analysis with the Yates correction.
The study times were tested for normality using the Kolmogorov-Smirnov goodness-of-fit test. Within-group comparisons of the study times were analyzed using the Kruskal-Wallis test with post hoc pairwise comparisons analyzed using the Mann-Whitney U test. Between-treatment comparisons of study times at the same CI level were also analyzed using the Mann-Whitney U test with unadjusted P values reported and interpreted relative to the critical P value of 0.05/3 or 0.017 to control for experiment-wise error. A P < 0.05 was considered statistically significant.
One hundred-fifty children were enrolled in the study (n = 75 children/group). Demographic data for the 2 groups were similar (Table 4). The frequency of medical conditions in the 2 groups was also similar: overall, 30 (20%) children received seizure medications, 17 (11%) were asthmatic, and 28 (19%) had a recent history of an URTI. Forty percent of the children presented with some degree of CI, although the frequency of CI in the 2 groups was similar (Table 4). The distribution of the scans was: 77% brain, 14% spine, and 9% extremities and pelvis (Table 4). All scans were completed, and none was repeated due to movement. The image quality in every scan was reported as good to excellent.
There were no adverse events in either group during maintenance of anesthesia; adverse events were detected only during emergence and recovery. The frequency of all adverse airway events in the children who received propofol (12%) was significantly less than in those who received isoflurane/N2O (49%) (P = 0.0001) (Table 5). Airway events, which occurred between scan completion and transport to the PACU, including airway obstruction, mild desaturation, other events, and those airway events that required intervention occurred significantly less frequently after propofol than those after isoflurane/N2O (Table 5). Adverse airway events (Table 2) responded quickly to 100% oxygen, continuous positive airways pressure, jaw thrust or inserting an oropharyngeal airway; neither succinylcholine nor bolus doses of propofol were required to treat laryngospasm. An oropharyngeal airway was not required in any children anesthetized with propofol but was required in 5 of those anesthetized with isoflurane/N2O/LMA. When the adverse airway events were stratified for CI, the need for airway intervention in children without CI (designated as “none” in Table 6), moderate/severe, and the combination of mild/moderate/severe in the propofol arm was significantly less than for the corresponding groups in the isoflurane/N2O/LMA arm (Table 6). The frequency of adverse airway events in children with a recent history of URTI or asthma in the 2 treatment groups was similar (Table 7).
The times for induction of anesthesia and to complete the MRI scans in the propofol and isoflurane/N2O/LMA groups were similar (bolded data under “Total” in Table 8). Early recovery, defined as the times between admission to PACU and either eye opening or full wakefulness, for all children who received propofol was significantly longer than the corresponding values for all children after isoflurane/N2O/LMA (entries under “Total” in Table 8). However, the times to discharge children from PACU, same day surgery, and the hospital after propofol and isoflurane/N2O/LMA were similar (Table 8). When the recovery times were stratified for CI, early recovery of children who were not cognitively impaired and of those who were moderately/severely impaired after propofol was significantly prolonged compared with those after isoflurane/N2O/LMA (Table 8).
The frequency of nausea and/or vomiting after propofol, 3%, was significantly less than that after isoflurane/N2O, 17%, (P = 0.0049). The 95% confidence interval for the risk difference (14%) was 5.7% to 25.2%. The majority (93%) of nausea occurred in the PACU; 2 children who received propofol required ondansetron compared with 12 who received isoflurane/N2O/LMA.
Mean systolic blood pressure during the MRI decreased significantly with time and the interaction, treatment × time (Fig. 1). Seventeen children experienced a decrease in arterial blood pressure >25% below baseline: 8 who were anesthetized with propofol and 9 who were anesthetized with isoflurane/N2O. Only 1 child who received isoflurane/N2O required interventions, which included a fluid bolus and a decrease in the concentration of isoflurane by 0.25%.
Mean heart rate in both groups decreased significantly during the MRI scan; there were main effects of treatment and time, but not an interaction (Fig. 2). The slowest heart rate in the children who received propofol was 62 bpm and in those who received isoflurane/N2O was 56 bpm. Both episodes of bradycardia resolved spontaneously.
The ETCO2 increased significantly during the scanning period (Fig. 3). There were significant main effects of both treatment and time, and the interaction, treatment × time (P = 0.0086). The mean EtCO2 in the children anesthetized with propofol was statistically significantly less than the EtCO2 in those anesthetized with isoflurane/N2O (Fig. 3). The EtCO2 readings <25 mm Hg were sustained and consistent in 13 children who received propofol compared with one who received isoflurane/N2O (P = 0.001). In addition, variability in the waveform of the capnogram in children anesthetized with propofol (n = 12) occurred significantly more frequently than in those anesthetized with isoflurane/N2O (n = 3) (P = 0.03).
Respiratory rate varied significantly during the scanning period (Fig. 4). Analysis revealed significant main effects of treatment, time, and the interaction, treatment × time (P = 0.019). The respiratory rate in those who received propofol during the MRI was significantly less than the rate in those who received isoflurane/N2O (Fig. 4).
Two children in the isoflurane/N2O/LMA group developed transient apnea before placement of the IV. In both children, the apnea resolved spontaneously. Neither hypoventilation nor hypercapnia was diagnosed in any child during the MRI scan or in the PACU. Hemoglobin oxygen saturation did not differ significantly between the 2 treatments either during the scan or recovery.
In the PACU, there was a significant effect of treatment only, for systolic blood pressure and heart rate. Overall, the systolic blood pressure (P = 0.00001) and heart rate (P = 0.00001) in the children anesthetized with propofol were less than those anesthetized with isoflurane/N2O. These differences were not clinically significant and required no interventions. Respiratory rate did not change significantly in either treatment group.
In the postdischarge follow-up phone calls, 1 child who had received propofol was sleepy and a second had a red rash on the face, whereas 3 children who had received isoflurane/N2O vomited and 1 child developed a red rash on the face. The 2 children with red rashes on their faces were scanned 1 week apart, the scans lasted <1 hour in duration, and they were without notable complications by the healthcare team. The rashes were not reported by the nurses in PACU and thus must have developed after discharge from PACU. The rashes were evident on the face only and were not pruritic, raised, or blotchy according to the parents. They were not in areas where tape had been applied and were not deemed to be drug reactions. Monitoring wires were not near or on the face, a common cause of burns during MRI. Both parents gave their children diphenhydramine without improvement. By the first postanesthetic day, the skin rashes had disappeared. We were advised that the new 1.5 Tesla MRI scanner was the most likely cause for the rashes. The manufacturer’s technical support staff investigated the scanner and concluded it was operating properly. No further explanation for the burns was provided. All parents were satisfied with the anesthesia technique that their child had received.
The primary purpose of this study was to compare the frequency of adverse events after propofol anesthesia with oxygen by nasal cannula with those after isoflurane with 70% N2O delivered via an LMA in children undergoing MRI scanning. We determined that the frequency of adverse events, in particular adverse airway events, during emergence/recovery from propofol anesthesia with a nasal cannula to deliver oxygen was significantly less than that after isoflurane/N2O/LMA. With respect to the secondary outcomes, cardiorespiratory responses were similar between the 2 treatments, although the frequency of vomiting after propofol was significantly less than after isoflurane/N2O/LMA. All clinical indices of recovery were similar for the 2 treatments including the time to discharge from hospital and unexpected hospital admissions.
The difference in the frequency of adverse airway events between the 2 anesthetic regimens was greater than expected (Tables 5 and 6). However, the frequency of adverse airway events is consistent with those reported for the 2 anesthetics.2,16,17,19 In the case of propofol with nasal cannula, avoiding a supraglottic airway may reduce the frequency of upper airway adverse events. Furthermore, in a model of upper airway irritability using saline to trigger apnea and laryngospasm, the incidence of acute airway responses during propofol anesthesia was significantly less than during sevoflurane anesthesia, independent of the depth of anesthesia.20 A similar model with isoflurane has not been evaluated, but isoflurane is known to irritate the upper airway in children.16,21,22 Furthermore, we removed the LMA at a deep level of anesthesia, a maneuver that has been associated with fewer adverse airway events than its removal in the awake state.16,23 This may have further decreased the difference in the rates of adverse airway events between the 2 treatments. The smaller frequency of desaturation after propofol may be attributed, in part, to the limited atelectasis reported after propofol anesthesia in spontaneously breathing children.24
The frequency of airway complications in children with CI in the current study was similar to those without CI (Table 6), although a previous study reported a 3-fold greater frequency of hypoxia between those with and without CI.13 This was not a primary outcome of the current study and could reflect a type II statistical error.
In the present study, none of the scans had to be repeated because of movement. This contrasts with several published studies in which children who were sedated with propofol required repeat scans because the children moved.3,6,7,25,26 The larger dose of propofol used in the current study is the most likely explanation for this difference in the incidence of movement.6,7,25–27
Although both anesthetic regimens provided an adequate depth of anesthesia to complete the scans, lack of movement and respiratory and circulatory indices cannot distinguish which anesthetic regimen provided a greater or lesser depth of anesthesia than the other.28 A single measurement using a depth of anesthesia monitor after egress from the scan room or the use of a sedation scale might have provided some evidence that one of the regimens maintained a different level of anesthesia from the other, but these assessments were not undertaken in the current study.
In contrast to previously published studies,10,29 we did not find a significant difference in the frequency of adverse airway events in children with a history of a recent URTI or asthma in either group compared with those without these diseases. The absence of a statistically significant difference in the frequency of adverse respiratory events may be explained by several factors including the anesthesiologist’s skills, the definition of a URTI and asthma, the criteria used to cancel an anesthetic, and the small sample size that might have introduced a Type II statistical error.
A blunted, distorted, or absent nasal capnogram did not present a major problem for respiration in those who were anesthetized with propofol. Nasal capnography has limitations in spontaneously breathing children, and even though 18% of the children who were monitored with nasal cannulae showed either a diminished, irregular, or absent capnogram trace, oxygen saturation was maintained and the scans were unaffected.27 Shifting breathing from the nose to the mouth is common in children who are anesthetized with propofol and breathing spontaneously. Such a finding is easily diagnosed and resolved by repositioning the nasal cannula between the lips. A second very important cause of a diminution in the nasal capnogram is an interruption in respiration, either breath-holding or apnea. In both instances, examination of the child’s breathing pattern will usually help to diagnose mouth breathing, for which the nasal cannulae should be moved to lie between the lips. If the airway is obstructed, a jaw lift should be applied and the neck position adjusted. If apnea is diagnosed, the dose of anesthetic should be reduced.
There are several weaknesses in this study that merit comment. The dose of propofol selected for the infusion rate was based on our personal experience to achieve as close to 100% success in completing the scans without movement. Smaller infusion rates may have abbreviated the emergence and recovery times, although they may have resulted in movement during scans particularly in younger children and in those who have CI.6,7,25–27
A second weakness relates to the use of only 1 anesthesiologist to provide the patient care and airway management and to 1 observer to evaluate and record all events and data, practices that might be viewed as limiting the external validity of the results. Although these criticisms are valid, standardization of technique and practice in a research investigation ensures homogeneity in the study execution and data acquisition. In effect, the rigidity of the protocol precluded modifications by individual practitioners. In this particular study, the single anesthesiologist was equally familiar with both anesthetic regimens that were used for the MRI scans and regarded both techniques with equipoise. Finally, we posit that our results are actually strengthened by using 1 observer and avoiding interindividual variability in the assessment of the outcome measures.
Adverse events, most notably airway events, after propofol anesthesia with nasal cannula were less frequent than after isoflurane/N2O/LMA, although hemodynamic responses and recovery characteristics were similar. These data favor the use of a propofol infusion with supplemental oxygen by nasal cannula for healthy children without active URTIs undergoing anesthesia for MRI scans and other nonpainful procedures approximately 1 hour in duration, particularly in remote locations.
Name: Christopher Heard, MBChB, FRCA.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Attestation: Christopher Heard has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Michael Harutunians, MD.
Contribution: This author helped conduct the study.
Attestation: Michael Harutunians reviewed the original study data.
Name: James Houck, MD.
Contribution: This author helped conduct the study.
Attestation: James Houck has seen the original study data and approved the current manuscript.
Name: Prashant Joshi, MD.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Prashant Joshi has seen the original study data and approved the current manuscript.
Name: Kristin Johnson, BS, PharmD, BCPS.
Contribution: This author helped design the study and conduct the study.
Attestation: Kristin Johnson has seen the original study data and approved the current manuscript.
Name: Jerrold Lerman, MD, FRCPC, FANZCA.
Contribution: This author helped design the study, analyze the data, and write the manuscript.
Attestation: Jerrold Lerman has seen the original study data, reviewed and analyzed the data, approved the current manuscript, and is the author responsible for archiving the study files.
This manuscript was handled by: Peter J. Davis, MD.
We thank Dr. Timothy T. Houle, PhD, Associate Professor, Department of Anesthesiology, Wake Forest Medical School, Winston-Salem, NC, for his expert advice and contributions to the statistical analysis of the data in this study.
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© 2015 International Anesthesia Research Society
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