A retrospective study of sedation and analgesic requirements of pediatric patients on extracorporeal membrane oxygenation (ECMO) from a single-center experience.

INTRODUCTION: The purpose of this study is to describe the sedative and analgesic requirements identifying factors associated with medication escalation in neonates and children supported on ECMO. METHOD: Observational retrospective cohort study in a tertiary pediatric intensive care unit from June 2009 to June 2013. RESULTS: One hundred and sixty patients were included in the study. Fentanyl and midazolam were the first line agents used while on ECMO. Higher opiate requirements were associated with younger age (p=0.01), thoracic cannulation (p=0.002), the use of dexmedetomidine (p=0.007) and prolonged use of muscle relaxants (p=0.03). Higher benzodiazepine requirements were associated with younger age (p=0.01), respiratory failure (p=0.02) and the use of second line agents (p=0.002). One third of the patients required second line agents as adjuvants for comfort without a decrease in opiate and/or benzodiazepine requirements. CONCLUSIONS: Providing comfort to subpopulations of pediatric ECMO patients seems to be more challenging. The use of second line agents did not improve comfort in our cohort. Prospective studies are required to optimize analgesia and sedation management in children on ECMO.

Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.

Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can aid in identifying this condition, although their relationship to the clinical manifestations is not known. Herein we describe clinical and laboratory findings in two fraternal twins with hawkinsinuria who presented with failure to thrive and metabolic acidosis. Close clinical follow-up and laboratory testing revealed previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia, and anemia, along with the characteristic urinary metabolites, including massive pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal growth and normalized or improved most biochemical parameters. The dramatic response to NAC therapy supports the idea that glutathione depletion plays a key role in the pathogenesis of hawkinsinuria.

Ileal-pouch anal anastomosis in pediatric NSQIP: Does a laparoscopic approach reduce complications and length of stay?

PURPOSE: The purpose of this study was to determine if a laparoscopic approach reduces complications and length of stay (LOS) after total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA) in pediatric patients using a multicenter prospective database. METHODS: The American College of Surgeons National Surgical Quality Improvement Project Pediatric database from 2012 to 2015 was used to identify patients with a diagnosis of chronic ulcerative colitis (CUC) or familial adenomatous polyposis (FAP) undergoing TPC-IPAA. Major complications, minor complications, and prolonged LOS were compared based on laparoscopic versus open approach. RESULTS: 195 (108 female) patients underwent TPC-IPAA at a median age of 14 years (IQR: 11-16) for CUC (N = 99) or FAP (N = 96). Two-thirds of cases were laparoscopic. A laparoscopic approach was not associated with major complications, but lower odds of minor complications were observed. A reduced LOS was seen in laparoscopic versus open surgery (median LOS 6 vs 8 days, p < 0.01). Open IPAA was independently associated with prolonged LOS (>9 days) in the FAP cohort (OR 4.0, 95% CI 1.1-14.0). CONCLUSION: A laparoscopic approach was not associated with increased major complications but was associated with lower odds of minor complications and shorter LOS. The laparoscopic approach should continue to be preferred for pouch procedures in pediatric patients. TYPE OF STUDY: Treatment; retrospective study. LEVEL OF EVIDENCE: Level III.

Use of radiotracer labeling of pulmonary nodules to facilitate excisional biopsy and metastasectomy in children with solid tumors.

PURPOSE: Excision of suspected pulmonary metastases in children is challenging in the setting of multiple nodules or nodules that are small, deep, or soft. This study describes preoperative technetium macro-aggregated albumin (Tc 99m MAA) localization of pulmonary lesions to aid in intraoperative identification and resection. METHODS: Patients with past or present pediatric solid tumors who underwent resection of pulmonary nodules following CT-guided Tc 99m MAA labeling were identified. The primary outcomes were successful preoperative localization and subsequent resection. RESULTS: Metastasectomy following Tc 99m MAA localization was performed 15 times in 11 patients from 2014 to 2016. Mean age was 13years; the most common diagnosis was osteosarcoma (33%). Tc 99m MAA labeling was attempted in 24 nodules with mean nodule diameter 6±5mm and mean depth from the pleural surface of 12±17mm; localization was successful in 23 nodules (96%). Subsequent resection was performed by thoracotomy in 12 cases and thoracoscopy in 3. All labeled nodules were identified intraoperatively; two were not resected and 17 of the 21 nodules resected demonstrated metastatic disease on pathology. CONCLUSION: Tc 99m MAA labeling of pulmonary nodules in children is effective in facilitating resection of sub-centimeter intraparenchymal metastases identified on preoperative imaging. Furthermore, this technique allows for thoracoscopic metastasectomy in select patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Case Series/Level IV.

Multicenter study of crystalloid boluses and transfusion in pediatric trauma-When to go to blood?

BACKGROUND: The 9th edition of Advanced Trauma Life Support recommends up to three crystalloid boluses in pediatric trauma patients with consideration of transfusion after the second bolus; however, this approach is debated. We aimed to determine if requirement of more than one fluid bolus predicts the need for transfusion. METHODS: The 2010 to 2016 highest tier activation patients younger than 15 years from two ACS Level I pediatric trauma centers were identified from prospectively maintained trauma databases. Those with a shock index (heart rate/systolic blood pressure) greater than 0.9 were included. Crystalloid boluses (20 ± 10 mL/kg) and transfusions administered prehospital and within 12 hours of hospital arrival were determined. Univariate and multivariable analyses were conducted to determine association between crystalloid volume and transfusion. RESULTS: Among 208 patients, the mean age was 5 ± 4 years (60% male), 91% sustained blunt injuries, and median (interquartile range) Injury Severity Score was 11 (6,25). Twenty-nine percent received one bolus, 17% received two, and 10% received at least three. Transfusion of any blood product occurred in 50 (24%) patients; mean (range) red blood cells was 23 (0-89) mL/kg, plasma 8 (0-69), and platelets 1 (0-18). The likelihood of transfusion increased logarithmically from 11% to 43% for those requiring 2 or more boluses (Fig. 1). This relationship persisted on multivariable analysis that adjusted for institution, age, and shock index with good discrimination (Area under the Receiver Operating Characteristic, 0.84). Shock index was also strongly associated with transfusion. CONCLUSION: Almost half of pediatric trauma patients with elevated shock index require transfusion following two crystalloid boluses and the odds of requiring a transfusion plateau at this point in resuscitation. This supports consideration of blood with the second bolus in conjunction with shock index though prospective studies are needed to confirm this and its impact on outcomes. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Regional Cerebral Abnormalities Measured by Frequency-Domain Near-Infrared Spectroscopy in Pediatric Patients During Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of advanced cardiorespiratory support provided to critically ill patients with severe respiratory or cardiovascular failure. While children undergoing ECMO therapy have significant risk for neurological morbidity, currently there is a lack of reliable bedside tool to detect the neurologic events for patients on ECMO. This study assessed the feasibility of frequency-domain near-infrared spectroscopy (NIRS) for detection of intracranial complications during ECMO therapy. The frequency-domain NIRS device measured the absorption coefficient (µa) and reduced scattering coefficient (µs') at six cranial positions from seven pediatric patients (0-16 years) during ECMO support and five healthy controls (2-14 years). Regional abnormalities in both absorption and scattering were identified among ECMO patients. A main finding in this study is that the abnormalities in scattering appear to be associated with lower-than-normal µs' values in regional areas of the brain. Because light scattering originates from the intracellular structures (such as nuclei and mitochondria), a reduction in scattering primarily reflects loss or decreased density of the brain matter. The results from this study indicate a potential to use the frequency-domain NIRS as a safe and complementary technology for detection of intracranial complications during ECMO therapy.

Rates and risk factors of unplanned 30-day readmission following general and thoracic pediatric surgical procedures.

BACKGROUND/PURPOSE: Postoperative unplanned readmissions are costly and decrease patient satisfaction; however, little is known about this complication in pediatric surgery. The purpose of this study was to determine rates and predictors of unplanned readmission in a multi-institutional cohort of pediatric surgical patients. METHODS: Unplanned 30-day readmissions following general and thoracic surgical procedures in children <18 were identified from the 2012-2014 National Surgical Quality Improvement Program- Pediatric. Time-dependent rates of readmission per 30 person-days were determined to account for varied postoperative length of stay (pLOS). Patients were randomly divided into 70% derivation and 30% validation cohorts which were used for creation and validation of a risk model for readmission. RESULTS: Readmission occurred in 1948 (3.6%) of 54,870 children for a rate of 4.3% per 30 person-days. Adjusted predictors of readmission included hepatobiliary procedures, increased wound class, operative duration, complications, and pLOS. The predictive model discriminated well in the derivation and validation cohorts (AUROC 0.710 and 0.701) with good calibration between observed and expected readmission events in both cohorts (p>.05). CONCLUSIONS: Unplanned readmission occurs less frequently in pediatric surgery than what is described in adults, calling into question its use as a quality indicator in this population. Factors that predict readmission including type of procedure, complications, and pLOS can be used to identify at-risk children and develop prevention strategies. LEVEL OF EVIDENCE: III.

Comparison of Lecture-Based Learning vs Discussion-Based Learning in Undergraduate Medical Students.

OBJECTIVE: To compare lecture-based learning (LBL) and discussion-based learning (DBL) by assessing immediate and long-term knowledge retention and application of practical knowledge in third- and fourth-year medical students. DESIGN: A prospective, randomized control trial was designed to study the effects of DBL. Medical students were randomly assigned to intervention (DBL) or control (LBL) groups. Both the groups were instructed regarding the management of gastroschisis. The control group received a PowerPoint presentation, whereas the intervention group was guided only by an objectives list and a gastroschisis model. Students were evaluated using a multiple-choice pretest (Pre-Test MC) immediately before the teaching session, a posttest (Post-Test MC) following the session, and a follow-up test (Follow-Up MC) at 3 months. A practical examination (PE), which tested simple skills and management decisions, was administered at the end of the clerkship (Initial PE) and at 3 months after clerkship (Follow-Up PE). Students were also given a self-evaluation immediately following the Post-Test MC to gauge satisfaction and comfort level in the management of gastroschisis. SETTING: University of Iowa Hospitals and Clinics and the Carver College of Medicine, Iowa City, IA. PARTICIPANTS: A total of 49 third- and fourth-year medical students who were enrolled in the general surgery clerkship were eligible for this study. Enrollment into the study was completely voluntary. Of the 49 eligible students, 36 students agreed to participate in the study, and 27 completed the study. RESULTS: Mean scores for the Pre-Test MC, Post-Test MC, and Follow-Up MC were similar between the control and intervention groups. In the control group, the Post-Test MC scores were significantly greater than Pre-Test MC scores (8.92 ± 0.79 vs 4.00 ± 1.04, p < 0.0001), whereas the Follow-Up MC scores were significantly lower than Post-Test MC scores (7.17 ± 1.75 vs 8.92 ± 0.79, p = 0.005). In the control group, the Follow-Up MC scores were significantly greater than Pre-Test MC scores (7.17 ± 1.75 vs 4.00 ± 1.04, p < 0.0001). Analysis of variance for all control group MC examinations had a p < 0.0001. In the intervention group, the Post-Test MC scores were significantly greater than Pre-Test MC scores (8.33 ± 1.23 vs 4.60 ± 1.55, p < 0.0001), whereas the Follow-Up MC scores were significantly lower than Post-Test MC scores (7.13 ± 1.77 vs 8.33 ± 1.23, p = 0.04). In the intervention group, the Follow-Up MC scores were significantly greater than Pre-Test MC scores (7.13 ± 1.77 vs 4.60 ± 1.55, p = 0.0002). Analysis of variance for all intervention group MC examinations had a p < 0.0001. Mean scores for the Initial PE were significantly higher for the intervention group compared with the control group's score (7.47 ± 1.68 vs 5.25 ± 2.34, p = 0.008). Mean scores for the Follow-Up PE were significantly higher for the intervention group compared with the control group's score (7.87 ± 1.77 vs 5.83 ± 2.04, p = 0.005). A comparison of Initial PE vs Follow-Up PE was not significant in either group. Students in the intervention group were more comfortable in the immediate management of gastroschisis and placement of a silo and felt that the educational experience was more worthwhile than students in the control group did. CONCLUSIONS: After a single instructional session, there was a significant difference in the students' scores between the control and the intervention groups on both administrations of the PEs. There were no significant differences between the 2 groups in any administration of the MC examinations. This seems to suggest that DBL may lead to better practical knowledge and potentially improved long-term knowledge retention when compared with LBL. Students in the DBL group also felt more comfortable with the management of gastroschisis and were more satisfied with the educational session.

Thoracoscopic Vs open resection of congenital cystic lung disease- utilization and outcomes in 1120 children in the United States.

PURPOSE: To determine if utilization of thoracoscopic resection of congenital cystic lung disease (CLD) is increasing and if this approach is associated with improved outcomes using a large national sample. METHODS: Children ≤20years old who underwent resection of a congenital cystic adenomatoid malformation, bronchopulmonary sequestration, or bronchogenic cyst were identified from the Healthcare Cost and Utilization Project Kids' Inpatient Database (2009, 2012) and Nationwide Inpatient Sample (2008, 2010-2011). Patient characteristics and outcomes were compared between thoracoscopic and open approaches using univariate and multivariable analyses stratified by magnitude of resection. RESULTS: Thoracoscopic resection was used in 39.4% of 1120 children who underwent resection of CLD. Utilization of the thoracoscopic approach increased from 32.2% in 2008 to 48.2% in 2012. Use of thoracoscopy was lower in lobectomy than segmental resection (32.5 vs 48.4%, p<.001). Newborns, those with comorbid congenital conditions, and those with respiratory infections also had lower rates of thoracoscopy. After stratifying by magnitude of resection and adjusting for patient complexity, complication rates and postoperative length of stay were similar between thoracoscopic and open approaches. CONCLUSION: Utilization of thoracoscopic resection for CLD in the United States is increasing with time. After adjusting for patient complexity, there is no difference in postoperative length of stay or complications between thoracoscopic and open lobectomy and sub-lobar resection.

Alternative schedules of levothyroxine administration.

PURPOSE: Published evidence on bedtime versus prebreakfast administration of levothyroxine is reviewed. SUMMARY: Because levothyroxine absorption has been shown to increase when the drug is administered to patients in a fasted state, the standard recommendation is that levothyroxine be taken one half to one hour prior to breakfast and at least four hours before or after potentially interacting drugs. However, compliance with this recommendation may be problematic for patients with unpredictable or variable schedules. A literature search identified four published studies of bedtime levothyroxine dosing. Two of the studies demonstrated a significant decrease in levels of thyroid-stimulating hormone (TSH) with levothyroxine administration at bedtime versus 30 minutes before breakfast, one study showed an increase in TSH when levothyroxine was taken at bedtime versus one hour before breakfast, and one study found no significant differences in TSH levels or other thyroid function monitoring limitations with bedtime versus standard dosing in subjects naive to levothyroxine therapy. The inconsistent study findings may be attributable to a number of variables, including dietary differences among the study populations, the use of potentially interacting supplements in one study, and variable intervals between levothyroxine administration and food intake. Neither dosing method correlated with substantial changes in assessments of quality of life or symptom severity; in two of the studies, patients indicated a preference for bedtime levothyroxine administration. CONCLUSION: Based on the available literature, bedtime administration of levothyroxine is an option for patients with hypothyroidism who want to avoid taking their medication with food.

Long-term outcomes of ileal pouch-anal anastomosis for pediatric chronic ulcerative colitis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with chronic ulcerative colitis (CUC). In the pediatric population, short-term outcomes of IPAA are excellent but long-term data limited. The purpose of this study is to report long-term functional and quality of life outcomes of IPAA in pediatric patients. METHODS: Functional outcomes and quality of life (QoL) following IPAA in patients ≤ 18 years of age were prospectively assessed by survey over a 30 year period. Preoperative information, chronic pouchitis and pouch loss were retrospectively reviewed. RESULTS: Over 30 years, 202 children with CUC underwent IPAA. Questionnaires were returned by 87% and median (range) survey follow-up was 181.5 (7.8-378.5) months. Postoperative day and night-time stool frequency did not increase over time though incontinence increased slightly. Quality of life (QoL) was generally excellent and stable over time. Crohn's disease (CD) was diagnosed in 33 (16%) patients during the follow-up period. Chronic pouchitis occurred in 22 patients and pouch failure in 13 patients. Kaplan Meier estimates of pouch survival at 20 years were 61% for patients with CD and 92% for CUC. CONCLUSIONS: Ileal pouch-anal anastomosis has long-term durability as a cure for pediatric chronic ulcerative colitis, with most patients reporting stable bowel function and QoL. Chronic pouchitis and pouch failure affect a minority of patients and require further study.

Single-incision laparoscopic colon and rectal surgery for pediatric inflammatory bowel disease and polyposis syndromes.

BACKGROUND: Minimally invasive procedures for inflammatory bowel disease have been shown to improve recovery in children. We report our initial experience with single-incision laparoscopic operations for pediatric intestinal disease. METHODS: We retrospectively reviewed 12 procedures in 11 patients (4 women) from March 2010 to January 2011. Procedures were conducted by using standard laparoscopic instruments. RESULTS: Mean age was 15 years (9-17 years). Procedures included three total abdominal colectomies, four two-stage ileal-pouch anal anastomosis (IPAA), two single-stage IPAA, two three-stage IPAA, and one ileocectomy. An accessory umbilical port was used in 6 cases. Mean operating time was 287 minutes. Mean length of stay was 4.1 days (3-9 days). Postoperative complications have occurred in 5 patients (42%). Anastomotic leak occurred in 2 patients with IPAA without protective ileostomy, 1 operative small bowel obstruction, 1 pelvic abscess and portal vein thrombosis, and 1 readmission for dehydration. Both patients who had leaked have recovered well and had their stomas reversed. Mean follow-up is 190 days. Average number of daily bowel movements is 4.5. Pouchitis has occurred in 50% (4/8) of patients. CONCLUSIONS: Single-incision laparoscopic surgery for pediatric intestinal disease is safe and feasible by using standard laparoscopic instruments. We do not advocate IPAA without a stoma due to the high rate of anastomotic leak. Continued experience will shorten operative times and reduce complications.

Role of twenty-four-hour ambulatory blood pressure monitoring in children on dialysis.

BACKGROUND AND OBJECTIVES: Pre- or postdialysis BP recordings are imprecise, can be biased, and have poor test-retest reliability in children on dialysis. We aimed to examine the possible differences between pre- and postdialysis BP levels and 24-hour ambulatory BP monitoring (ABPM) in diagnosis of hypertension (HTN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four children on dialysis had 24-hour ABPM in the interdialytic period, and values were compared with average pre- and postdialysis systolic BP (SBP) and diastolic BP (DBP) recordings that week. Each patient had an echocardiogram to determine presence of left ventricular hypertrophy (LVH). RESULTS: By ABPM, 8% of patients had white coat HTN and 12% had masked HTN. There was no significant difference in diagnosis of systolic HTN based on ABPM daytime SBP mean or load and postdialysis SBP. However, only 15% of patients had diastolic HTN based on postdialysis measures, whereas 46% of patients had significantly elevated daytime DBP loads and 71% had high nighttime DBP loads on ABPM. Forty-eight percent of patients were SBP nondippers. Children with LVH had higher daytime and nighttime SBP loads, significantly higher daytime and nighttime DBP loads, and lesser degree of nocturnal dipping of SBP compared with those who did not. CONCLUSION: ABPM is more informative than pre- and postdialysis BPs and improves the predictability of BP as a risk factor for target organ damage. Diagnosis and treatment monitoring of HTN among pediatric dialysis patients is enhanced with addition of ABPM.

Myocardial tagging and strain analysis at 3 Tesla: comparison with 1.5 Tesla imaging.

PURPOSE: To determine whether imaging at 3 T could improve and prolong the tag contrast compared to images acquired at 1.5 T in normal volunteers, and whether such improvement would translate into the ability to perform strain measurements in diastole. MATERIALS AND METHODS: Normal volunteers (N = 13) were scanned at 1.5 T (GE Signa CV/i) and 3.0 T (GE VH/i). An ECG-triggered, segmented k-space, spoiled-gradient-echo grid-tagged sequence was used during cine acquisition. Tag contrast was determined by the difference of the mean signal intensity (SI) of the tagline to the mean SI of the myocardium divided by the standard deviation (SD) of the noise (CNR(tag)). Matched short-axis (SA) slices were analyzed. Strain measurements were performed on images using a 2D strain analysis software program (harmonic phase (HARP)). RESULTS: The average CNR(tag) over the cardiac cycle was superior at 3 T compared to 1.5 T for all slices (3 T: 23.4 +/- 12.1, 1.5 T: 9.8 +/- 8.4; P < 0.0001). This difference remained significant at cycle initiation, end-systole, and the end R-R interval (at cycle termination: 3 T = 14.0 +/- 11.0 vs. 1.5 T = 4.4 +/- 3.5; P < 0.01). Strain measures were obtainable only in early systole for 1.5 T images, but were robust throughout the entire R-R interval for 3 T images. CONCLUSION: Imaging at 3 T had a significant benefit for myocardial tag persistence through the cardiac cycle. The improvement allowed strain analysis to be performed into diastole.