Sedation and Analgesia for Reduction of Pediatric Ileocolic Intussusception

This cross-sectional study characterizes the prevalence of opioid analgesia and sedation among children undergoing reduction of ileocolic intussusception and assesses their association with intestinal perforation and failed reduction.


Introduction
Ileocolic intussusception refers to the invagination of the ileum through the ileocecal valve into the cecum. 1 With a yearly incidence of approximately 56 of 100 000, ileocolic intussusception is an important cause of acute intestinal obstruction in children younger than 6 years. 2 If untreated, intussusception can result in tissue ischemia, potentially leading to bowel necrosis, perforation, and shock. 3 In countries with higher resources, case fatality is less than 1%, 1 while it may be as high as 9% in nations with fewer resources. 3 Transabdominal ultrasonography is the diagnostic modality of choice due to its high sensitivity (98%), safety, and availability. 4 Emergent reduction of ileocolic intussusception using air or hydrostatic enema is the standard of care to prevent complications. 5 Reduction involves inserting a French Foley catheter into the rectum and instilling water or air under pressure into the colon. 5 No studies have objectively quantified pain during reduction, but it is believed to be painful based on analogies with colonoscopy, where the bowel is also distended with gas and children usually require sedation. 6 In contrast, reduction of ileocolic intussusception is usually performed on awake children without sedation or analgesia. In the United States, only 7% of children with ileocolic intussusception receive sedation during reduction. 1 The risk of bowel perforation during reduction is less than 1%. 5 Although some studies report that sedation improves the success of intussusception reduction, 7-10 most American and European radiologists do not support this practice. 11,12 This may be due to requirements for specialized equipment, personnel skilled in airway maneuvers, or the belief that sedation may increase the risk of perforation during reduction. 13 The management and complications of reduction of intussusception vary considerably by country, 1 highlighting the importance of a global perspective of practice patterns to evaluate the risks of perforation during reduction and failed reduction related to sedation and analgesia. Our objective was to characterize practice patterns surrounding opioid analgesia and sedation for the reduction of ileocolic intussusception in children and to assess their association with intestinal perforation and failed reduction in an exploratory analysis.

Methods
This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. The institutional review board of each site approved the study and waived requirements for individual informed consent because patient data were deidentified.

Design Eligibility
We included patients aged 4 to 48 months with a sonographic diagnosis of ileocolic intussusception who underwent attempted reduction of intussusception. Medical records were consecutively identified through electronic queries at each institution. We excluded repeat presentations of intussusception.

Data Collection
Data were deidentified before being entered into an electronic case report form hosted on Research Electronic Data Capture (REDCap) 14 by a research assistant or coinvestigator at each site. One coinvestigator (D.M.) reviewed the data for accuracy. We collected demographics, symptoms, pain scores, analgesics and sedative medications, time to reduction, reduction parameters (pneumatic or hydrostatic reduction, insufflation pressure, personnel performing the procedure and training level, number of attempts, and success of reduction), sedation-and reduction-related adverse events, and operative management. Source documents included the medical record, anesthetic record, radiology, and operative reports. We defined analgesia as any pharmacologic nonsedative agent administered in the ED for pain management within 120 minutes prior to reduction (eg, ibuprofen, acetaminophen, opioids). We defined sedation as any pharmacologic agent with anxiolytic, sedative, dissociative, or anesthetic properties administered immediately prior to reduction (eg, ketamine, midazolam). Although some opioids (eg, morphine) have sedating properties, we elected to classify these as analgesics because we believed they were primarily used for this purpose. Time to reduction was measured from triage assessment to radiology department entry. A failed reduction was defined as all enema attempts failing to reduce intussusception as documented by the physician performing the procedure. Successful reduction was defined as such regardless of the number of enema attempts as documented by the physician performing the procedure. Adverse events were based on the Medical Dictionary of Regulatory Activities, 15 and recorded at any time during sedation or reduction from the physician or nursing anesthetic record.

Outcomes
The primary outcomes were opioid analgesia within 120 minutes of reduction based on the therapeutic window of IV morphine 16 and sedation immediately before reduction of intussusception.
Exploratory outcomes included associations between opioid analgesia and sedation and intestinal perforation during reduction and failed reduction.

Sample Size Considerations
Based on an expected incidence of intussusception in children (56 of 100 000), 2 the risk of perforation during reduction of 0.6%, 17 and the risk of failed reduction of 13.1%, 17 we believed our study period would capture 3000 to 3500 patient encounters and yield a sample size supporting a multivariable model with at most 2 factors for perforation and at most 32 factors for failed reduction in keeping with a general requirement of 10 to 12 covariates per outcome. 18

Statistical Analysis
Demographic characteristics were summarized with counts and percentages for categorical data and means and SDs or medians and interquartile ranges (IQRs) for continuous data. Bivariate and separate multivariable analyses were used to explore the associations between (1) perforation and the following prespecified covariates: age, sex, analgesia (opioids with or without nonopioid analgesics; nonopioid analgesics alone) at triage and within 120 minutes of reduction, triage pain assessment, sedation for reduction, opioids with or without nonopioid analgesics plus sedation, duration of symptoms prior to reduction, and number of reduction attempts and (2) failed enema reduction and the following prespecified covariates: age, sex, analgesia (opioids with or without nonopioid analgesics; nonopioid analgesics alone) at triage and within 120 minutes of reduction, sedation for reduction, opioids with or without nonopioid analgesics plus sedation, duration of symptoms prior to reduction, type of enema reduction (pneumatic vs hydrostatic), and preexisting gastrointestinal anomaly. Fentanyl was excluded from the opioid category for bivariate and multivariable modeling because we could not reliably ascertain that it was administered within its 60-minute therapeutic window. We included covariates in adjusted (multivariable) models if they were biologically plausible and had an unadjusted association with the outcome significant at a threshold of P < .05. Unadjusted bivariate and adjusted multivariable odds ratios (ORs) and 95% CIs were obtained from generalized mixed-effects logistic regression models with the factors of interest as fixed effects and site as a random effect using a simple variance components covariance structure with random intercept. Analyses were conducted using SPSS version 27 (IBM SPSS). A type I error rate of 0.05 was used to reject the null hypothesis of no association. All P values were 2-tailed. Data were analyzed using complete case analysis, and the analysis took place in August 2022.

Participants
Overall, 3555 records were screened, and 3203 were eligible and included in the analysis (2054

Sedation and Analgesia Within 120 Minutes of Reduction of Intussusception
Any analgesia was documented in 466 of 3175 patients (14.7%), and morphine was the most common analgesic used (276 of 466 [59.2%]) ( Table 3 and Table 4

Discussion
In this international cross-sectional study, more than two-thirds of children received neither analgesia nor sedation for the reduction of ileocolic intussusception. However, neither analgesia, sedation, nor their combination was associated with intestinal perforation or failed reduction. In fact, the strongest covariate associated with failed reduction was preexisting gastrointestinal anomaly.
Our results suggest the infrequency of provision of analgesia and sedation for this likely painful procedure and challenge the widespread practice of withholding analgesia and sedation.
Our perforation rate was consistent with a published rate of less than 1%, 5 and our results are corroborated by a recent systematic review 17 of 849 propofol-based sedations for reduction of intussusception in children where the incidence of intestinal perforation was 0.6%. Current reluctance to sedate children for reduction of intussusception appears to be common in the US 11 and Europe, 12 the source of most of our data and may stem from a study involving a porcine model where an induced Valsalva maneuver was deemed protective through decreasing transmural pressure with associated lower risk of perforation. 13 Due to the small number of perforations, we were unable to adjust for risk factors, such as high insufflation pressures (Ն120 mm Hg), 13 duration of symptoms for more than 12 hours, 19 lack of a Valsalva maneuver, 13 dehydration, 19 and younger age. 9 Adverse events were uncommon, but importantly, our study was not powered to detect all adverse events, and it was not possible to determine their exact cause, whether related to sedation, analgesia, or   b Odds ratios and 95% CIs compare the odds of failed reduction for each group vs the reference category, an increase in age by 1 month, an increase in number of reduction attempts by 1 attempt, or an increase in time to reduction by each 1-hour increment.

JAMA Network Open | Pediatrics
c P values test for a difference between any levels of a categorical factor, or for an odds ratio of zero for a continuous factor. d Analgesia data are available in eTable 1 of Supplement 1.
e Sedation for reduction data are available in eTable 2 of Supplement 1.
f Types of anomalies are listed in Table 2. procedure. Nevertheless, we found that neither opioid analgesia nor sedation within 2 hours of reduction was independently associated with perforation, in concert with the findings of Yeoh et al, 20 where opioid analgesia within 2 hours of reduction was provided to 65.8% of Australian children and no perforations were reported.
Only 9.6% and 14.9% of patients received analgesia at triage and within 120 minutes of reduction, respectively. Although abdominal pain is a frequent presenting feature of intussusception in children, 21 the most likely explanation for not providing analgesia at triage was low pain scores.
Fortunately, pain assessment was most often performed using the FLACC scale, an appropriate behavioral instrument validated in children younger than 5 years. 22 However, less than 60% of patients had a documented pain assessment. Along with being mandated by The Joint Commission, 23 the importance of consistent pain assessment using age-appropriate instruments cannot be overemphasized as these have been associated with a greater likelihood of receiving The frequency of failed reduction in our sample (15.2%) is consistent with previous reports. 19 The findings of a recent systematic review that included 1434 children who underwent sedation reported a success rate of 86.9% under sedation. 17 Our finding that neither analgesia nor sedation was associated with failed reduction is in line with evidence that sedation actually improves the success rate of both hydrostatic 7,8,10 and pneumatic enema reduction. 9,29 For reasons that remain uncertain, in the adjusted analysis, we found that older age and shorter duration of symptoms were associated with an increased odds of failed reduction. Importantly, the strength of these associations was very weak and future prospective studies should control for factors, such as clinician experience, length of intussusception, and duration of symptoms.
Our findings provide preliminary evidence that neither opioid analgesia nor sedation is associated with perforation or failed reduction. Although this may inform the decision to consider analgesia and sedation, there are no studies that have rigorously characterized the pain and distress associated with reduction of intussusception. Clinicians must also weigh the potential benefit of sedation for patient comfort with the need for specialized equipment, monitoring, and personnel trained in pediatric resuscitative maneuvers outside the acute care setting. Nevertheless, our work lays the foundation for future interventional studies that may provide definitive evidence of distress during reduction of intussusception and evaluate the risks and benefits of providing analgesia and sedation, while controlling for risk factors for perforation and failed reduction, such as age and clinician experience.

Limitations
This study had limitations. It is, to our knowledge, the largest study to date on this topic and provides a global perspective of children undergoing reduction of ileocolic intussusception who received sedation or opioid analgesia. Participating sites were primarily academic centers, where most reductions of intussusception in children are performed, and our results are likely only generalizable to these institutions. Due to the retrospective nature of the data, we were unable to characterize factors that may have influenced the provision of opioids and sedation, such as the timing of prehospital analgesia, inability to tolerate oral medication, and specific contraindications. We did not collect data on nonpharmacologic strategies, such as distraction that may have been facilitated by a caregiver or child life specialist. We were unable to characterize other possible risk factors for perforation and failed reduction, including degree of behavioral resistance during reduction, dehydration, duration of symptoms prior to reduction, length of intussusception, and clinician experience. This may have reduced the precision of our ORs. Pain during reduction may have been an important factor of failed reduction and perforation. This data was not available and highlights the importance of evaluating distress during reduction of intussusception. Most importantly, our results were highly dependent upon, and therefore limited to, the accuracy and completeness of the information contained in the medical record. Given that this was an unfunded global study, 2 blinded data abstractors at each site were not possible.

Conclusions
The findings of this multinational cross-sectional study suggest that reduction of pediatric ileocolic intussusception can be successfully performed in most children with a very low risk of perforation.
More than two-thirds of patients received neither sedation nor analgesia within 120 minutes of reduction. Our findings challenge the widespread practice of withholding analgesia and sedation and lay the foundation for future prospective studies exploring the benefits of sedation or analgesia for reduction of intussusception in children.

ARTICLE INFORMATION
Accepted for Publication: April 24, 2023.