'NOPAIN-ROP' trial: Intravenous fentanyl and intravenous ketamine for pain relief during laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants: A randomised trial.

OBJECTIVES: To investigate if intravenous fentanyl or intravenous ketamine can provide adequate analgesia in preterm infants undergoing laser photocoagulation for retinopathy of prematurity (ROP). DESIGN: Open-label randomised trial. SETTING: Tertiary care institution. PARTICIPANTS: Preterm infants who underwent laser photocoagulation for ROP. INTERVENTIONS: Infants were randomised to receive fentanyl as intravenous bolus dose of 2 µg/kg, followed by an intravenous infusion of 1 µg/kg/hour increased to a maximum of 3 µg/kg/hour or intravenous ketamine as bolus dose of 0.5 mg/kg, followed by further intermittent intravenous bolus doses of 0.5 mg/kg to a maximum of 2 mg/kg in the initial phase and intravenous fentanyl (bolus of 2 µg/kg followed by infusion of 2 µg/kg/hour to a maximum of 5 µg/kg/hour) or intravenous ketamine (bolus dose of 1 mg/kg followed by intermittent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) in the revised regimen phase. MAIN OUTCOME MEASURES: Proportion of infants with adequate analgesia defined as the presence of both: (1) all the Premature Infant Pain Profile-Revised scores measured every 15 min less than seven and (2) proportion of the procedure time the infant spent crying less than 5%.Secondary outcomes included apnoea, cardiorespiratory or haemodynamic instability, feed intolerance and urinary retention requiring catheterisation during and within 24 hours following the procedure. RESULTS: A total of 97 infants were randomised (fentanyl=51, ketamine=46). The proportions of infants with adequate analgesia were 16.3% (95% CI 8.5% to 29%) with fentanyl and 4.5% (95% CI 1.3% to 15.1%) with ketamine. Ten infants (19.6%) in the fentanyl group and seven infants (15.2%) in the ketamine group had one or more side effects. In view of inadequate analgesia with both the regimens, the study steering committee recommended using a higher dose of intravenous fentanyl and intravenous ketamine. Consequently, we enrolled 27 infants (fentanyl=13, ketamine=14). With revised regimens, the proportions of infants with adequate analgesia were higher: 23.1% (95% CI 8.2% to 50.2%) with fentanyl and 7.1% (95% CI 1.3% to 31.5%) with ketamine. However, higher proportions of infants developed apnoea (n=4; 30.7%), need for supplemental oxygen (n=5, 38.4%) and change in cardiorespiratory scores (n=7; 53.8%) with fentanyl but none with ketamine. CONCLUSIONS: Fentanyl-based and ketamine-based drug regimens provided adequate analgesia only in a minority of infants undergoing laser photocoagulation for ROP. More research is needed to find safe and effective regimens that can be employed in resource constrained settings. TRIAL REGISTRATION NUMBER: CTRI/2018/03/012878.

Diagnostic Accuracy of WINROP, CHOP-ROP and ROPScore in Detecting Type 1 Retinopathy of Prematurity.

BACKGROUND: Algorithms for predicting retinopathy of prematurity (ROP) requiring treatment need to be validated in Indian settings to determine if the burden of screening can be reduced without compromising the sensitivity of existing gestation and weight-based cut offs. OBJECTIVE: To evaluate the performance of the available algorithms namely, WINROP (Weight, Insulin-like growth factor I, Neonatal ROP), CHOP-ROP (Children's Hospital of Philadelphia ROP) and ROPScore in predicting type 1 ROP and time from alarm to treatment by each algorithm. STUDY DESIGN: Ambispective observational. SETTING: Tertiary care neonatal intensive care unit in India. PARTICIPANTS: Neonates less than 32 weeks or less than 1500 g born between July, 2013 to June, 2019 (N=578), who underwent ROP screening. PRIMARY OUTCOME: Sensitivity, specificity and time from alarm to treatment by each algorithm. RESULTS: The sensitivity and specificity of WINROP was 85% and 36%, for CHOP-ROP it was 54% and 71%, and for ROPScore it was 73% and 67%, respectively in detecting type 1 ROP. A total of 50/51 (98%) of neonates with type 1 ROP underwent treatment at median gestation of 9 weeks and median time from alarm to treatment by WINROP, CHOP-ROP and ROPScore was 7, 7 and 3 weeks, respectively. CONCLUSION: WINROP, CHOP-ROP and ROPScore were not sensitive enough to replace the gestational age, weight and risk factor-based screening criteria for type 1 ROP.

Non-immune Hydrops in Neonates: A Tertiary Care Center Experience.

OBJECTIVE: To evaluate the clinical profile and outcome of neonates with non-immune hydrops (NIH). METHODS: Data of all the NIH cases admitted to neonatal intensive care unit at our center, New Delhi from January, 2010 to October, 2017 were extracted from hospital records, which included clinical profile and outcomes. RESULTS: Of the 17,299 total births, 27 neonates were identified to have NIH. Antenatal interventions were undertaken in five (18.5%) cases. The most common etiology of NIH was cardiac (n=5; 18.5%). Two babies with chylothorax were successfully managed with octreotide infusions. Overall survival rate of NIH was 70.3% (n=19). All neonates with a suspected genetic syndrome died. CONCLUSIONS: Multidisciplinary team including obstetricians, pediatric surgeons, geneticists and neonatologists can improve outcome in neonates with NIH.

Quality improvement initiative for reduction of false alarms from multiparameter monitors in neonatal intensive care unit.

INTRODUCTION: Unnecessary and excessive activation of alarms ("false alarm") in neonatal intensive care unit (NICU) often results in alarm fatigue among health-care professionals, which can potentially result in deleterious effects in sick neonates. AIMS AND OBJECTIVES: The aim of this study is to reduce the frequency of false alarms from multiparameter monitors (MPM) by 50% from the existing baseline level over a period of 12 weeks. METHODS: In this quality improvement (QI) project conducted over 1 year (November 2016-October 2017) at All India Institute of Medical Sciences, New Delhi, we collected data on activation of false alarms from MPM (outcome measure) over a period of 2 months in 134 randomly selected observations of 1-h duration (baseline phase [10 days, 20 observations] and developing and testing the changes in five Plan-Do-study-Act (PDSA) cycles over the next 50 days, 114 observations. We also measured the pre- and postassessment of knowledge level in use of MPM among health-care professionals using checklist (process measure). Following that, we continued data collection for next 10 months to check sustenance of the project. RESULTS: Baseline characteristics including gestation, birth weight, and sickness level did not vary during the study period. The median (range) number of activation of false alarms/hour/MPM was 23 (18-35) in the baseline phase. This reduced to 22 (17-30), 19 (15-30), 16 (14-30), 14 (8-17), and 9 (6-12) at the end of 1st, 2nd, 3rd, 4th, and 5th PDSA cycles, respectively. In sustenance phase, it could be maintained in target range from January 2017 to October 2017. CONCLUSIONS: Small sustained changes can contribute a lot in continuous QI in decreasing false alarms and subsequent improvement of neurodevelopmental outcomes discharged neonates.

Long-acting intramuscular ACTH stimulation test for the diagnosis of secondary adrenal insufficiency in children.

Background The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children. Methods All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week. Results Forty-eight patients (36 boys/12 girls, age range: 5-14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 µg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 µg/dL [± 8.8] vs. 23.8 µg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 µg/dL (500 nmol/L) and <22 µg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively. Conclusions A peak cortisol value <18 µg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 µg/dL rules out SAI.