Preprocedural, intraprocedural, and postprocedural complications for all infants are described in Table 3. Oxyhemoglobin desaturation or need for supplemental oxygen was the most common complication. It was more prevalent during the procedure than in the postprocedure phase (19.6% vs 2.0%) because of the higher frequency of administration of supplemental oxygen by nursing personnel in response to gradually decreasing oxyhemoglobin saturations during the MRI scan. There was a sedation failure rate of 4.8%, whereby the MRI scan was unable to be successfully completed.
A comparison of dependent and independent variables between term and preterm infants was assessed by univariate analysis (Table 4). Preterm infants were more likely to be inpatients, have a lower weight, have a history of apnea, and have lower hemoglobin levels. The incidence of oxyhemoglobin desaturation <90% or the need for supplemental oxygen was approximately 20% in both term and preterm infants. Preterm infants were not more likely to develop postprocedure oxyhemoglobin desaturation than term infants (P = 0.2); however, because there were only 8 preterm infants who developed this complication, a type 2 error may have occurred because of the lack of sufficient statistical power. The clinical characteristics of these infants are detailed in Table 5.
There were 10 instances of postprocedural bradycardia in 8 infants (2 infants had a repeat MRI with CH sedation). Six (2.3%) involved preterm-born infants and there were 4 (0.4%) instances in term infants (P = 0.005). The PCA of the preterm infants ranged from 36 to 40 weeks, and the chronological age of the term infants ranged from 3 to 7 days. Three of the 10 episodes were associated with oxyhemoglobin desaturation. The nadir heart rates in these cases were 45 bpm, 78 bpm, and one unspecified. In the remaining 7 instances of bradycardia that were not associated with oxyhemoglobin desaturation, nadir heart rates ranged from 66 to 99 bpm. All resolved with physical stimulation.
We examined the influence of independent variables based on the occurrence of postprocedure oxyhemoglobin desaturation. Univariate analysis revealed that postprocedure oxyhemoglobin desaturation or need for supplemental oxygen was more likely in inpatients (P < 0.001) and was associated with a lower body weight (3.9 ± 2.1 kg vs 6.6 ± 3.0 kg; P < 0.001), history of apnea (33.3% vs 9.9%; P = 0.001), higher ASA physical status (P = 0.002), and younger chronological age (58.7 ± 82.8 days vs 152 ± 105.9 days; P < 0.0001; Fig. 2). Eighty-six infants (6.4%) in our cohort were classified as ASA physical status I (healthy without systemic disease), and none of these patients demonstrated postprocedure oxyhemoglobin desaturation or need for supplemental oxygen. Infants with postprocedural oxyhemoglobin desaturation tended to have higher hemoglobin levels (14.7 ± 3.8 g/dL vs 12.4 ± 3.0 g/dL; P = 0.035). In term and preterm infants, the presence of preprocedure or intraprocedure oxyhemoglobin desaturation was not associated with postprocedure oxyhemoglobin desaturation or need for supplemental oxygen. When the preterm group was analyzed separately, the risk of postprocedure oxyhemoglobin desaturation or need for supplemental oxygen was directly correlated with younger chronological age (56.0 ± 41.5 days vs 150.6 ± 107.1 days; P = 0.012) and younger PCA (39.5 ± 4.1 days vs 54.4 ± 15.2 days; P = 0.005), but not gestational age. Additional doses of CH or supplementation with midazolam also did not increase the incidence of postprocedural oxyhemoglobin desaturation or need for supplemental oxygen.
Chloral hydrate is a relatively mild sedative that, when administered orally in doses of 50 to 75 mg/kg, induces sleep without untoward respiratory or hemodynamic complications in most infants.14,15 However, in certain patients, CH has been associated with prolonged recovery and oxygen requirement.16 This is likely attributable to the relatively long half-life of its active metabolite, trichloroethanol, which is further delayed in preterm infants.10
Term infants younger than 1 month and preterm infants younger than approximately 48 to 60 weeks' PCA are at increased risk of developing central apnea after general anesthesia.1,3 It has become standard policy in most children's hospitals that these infants are admitted and monitored for at least 12 hours after administration of general anesthesia. Similar studies have not been performed to define the risk of apnea for at-risk infants who receive sedative drugs for medical procedures.
The most important findings in our analysis were that a relatively high proportion (approximately 20%) of both term and preterm infants required oxygen supplementation during the MRI scan, and the risk of postprocedure oxyhemoglobin desaturation or need for oxygen supplementation was directly correlated with younger chronological age in term infants, and directly correlated with lower weight, lower PCA, and younger chronological age in preterm infants. When compared with the term infant group, preterm infants did not have an increased incidence of postprocedure oxyhemoglobin desaturation or need for supplemental oxygen (P = 0.2). However, because this was a retrospective study, no a priori power estimates were performed. A post hoc power estimate revealed that with the current observation of postprocedure oxyhemoglobin desaturation or need for supplemental oxygen between preterm and full-term infants, we would need 5859 cases (1172 preterm and 4687 full term) to achieve 80% power to detect an absolute difference of 1.4% with a 5% level of significance using χ2 test. Thus, we cannot firmly accept the null hypothesis of similar rates of postprocedure oxyhemoglobin desaturation or need for supplemental oxygen between term and preterm groups. Bradycardia, however, was more common in preterm infants after the MRI scan. Allegaert et al.11 reported an increased incidence of bradycardia in former preterm infants who received CH. In their group, the development of bradycardia was associated with a younger gestational age but not a younger PCA.
When the group of infants who developed postsedation oxyhemoglobin desaturation or need for supplemental oxygen was examined more closely, several patterns are evident (Table 5). None of the preterm infants with postsedation oxyhemoglobin desaturation or need for supplemental oxygen was older than 48 weeks' PCA. All preterm infants with postprocedure oxyhemoglobin desaturation or need for supplemental oxygen were inpatients. In our group of term infants, there were 4 outpatients with relatively minor decreases in oxyhemoglobin saturation, and all were discharged home within several hours after the MRI scan completion. Six term infants required prolonged oxygen supplementation. None was older than 3 weeks, and all had significant comorbidities.
Previous studies that defined the risk of apnea after administration of general anesthesia were performed prospectively. Apnea was detected by using pneumography and nasal flow sensors.2 This prospective study design, although scientifically rigorous, is applicable for studying relatively small numbers of patients. A combined analysis was necessary to pool such studies for more meaningful results.3 By using the retrospective methodology in this study, we were not able to detect apnea, per se, but relied on the presence of oxyhemoglobin desaturation or requirement for additional oxygen administration as surrogate outcomes. The addition of supplemental oxygen did not have definite and consistent criteria throughout different locations in our institution, but, in exchange for using these surrogate outcomes, we were able to study a relatively large number of patients to determine relative risk of low chronological age, preterm birth, and other associated factors such as gestational age and PCA.
Our population of infants did not include those with congenital heart disease. At our institution, these patients are cared for and sedated by a separate service with separate sedation protocols.17 In addition, we thought that exclusion of this group was necessary to reduce bias from a population of infants at higher baseline risk for hypoxemia.18
There are additional limitations inherent in the use of a database populated by data obtained from electronic and paper-based patient records. The most important is the absence of documentation of important complications such as oxyhemoglobin desaturation. Thus, our incidence may be an underestimate of the true incidence, which could only be determined by prospective continuous observation. However, we expect that there is no bias toward underreporting based on the chronological age, gestational age, or PCA of our patients. Subjective complications such as upper airway obstruction, bronchospasm, laryngospasm, or flaccidity are also likely to be underestimated or documented to a lesser degree than would an objective number (i.e., Spo2) obtained from a patient monitor. Similarly, because discharge criteria were based on attainment of baseline clinical measures and not time per se, it is possible that some episodes of postdischarge oxyhemoglobin desaturation occurred. These limitations underscore the importance of carefully designed prospective studies to definitively investigate the effects of a variety of types of sedatives on postprocedural complications. Another possible limitation that is particular to this study is the lack of data after discharge from the MRI facility. Vital signs and oxygen requirements are recorded on the nurses' flow sheets up until the time of discharge, but there was no mechanism to identify subsequent sedation-related problems after discharge, such as subclinical oxyhemoglobin desaturation that self-resolved or did not result in an obvious change in the infant's health.
Finally, when considering important complications that guide clinical care, the interpretation of zero numerators must be done with extreme caution.19 For example, if one uses the case of the 86 ASA physical status I patients who did not develop postprocedure oxygen desaturation, the Hanley-Lippman-Hand rule of 3s predicts that we can be 95% confident that the rate of zero complications in this group is not >3 of 86, or approximately 3.5%. It is conceivable that healthy term infants may be safely discharged home without extended monitoring, but because CH causes delayed sedation after discharge home,16 communication with caretakers until the following day is essential. The inpatients in our study group had the advantage of documented vital signs over the postprocedure 24-hour period, but these data were impossible to know for outpatients.
In conclusion, the occurrence of postprocedural oxyhemoglobin desaturation that we were able to detect or need for supplemental oxygen was directly correlated with younger chronological age in term infants and younger PCA in preterm infants. Term infants who developed extended postprocedural hypoxemia were inpatients and had significant comorbidities. Preterm infants had a higher incidence of postprocedure bradycardia.
The authors are grateful to Mary Beth Bartko, MSN, Nurse Coordinator in the Department of Radiology, The Children's Hospital of Philadelphia, for providing the original database. They also acknowledge the invaluable assistance of research assistants in the Department of Anesthesiology and Critical Care at The Children's Hospital of Philadelphia: Sina Shah-Hosseini, MSE, Jared Mendelsohn, BS, Sabaa Dam, BS, and Reshma Pachikara, BS.
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© 2010 International Anesthesia Research Society
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