Berens et al. (1515. Berens RJ, Meyer MT, Mikhailov TA, Colpaert KD, Czarnecki ML, Ghanayem NS, et al. A prospective evaluation of opioid weaning in opioid-dependent pediatric critical care patients. Anesth Analg. 2006;102(4):1045-50.) |
Clinical trial (IB) |
n=37, ≤ 18 yrs |
Switch over fentanyl or morphine to enteral methadone using an initial dosage (“attack dosage ”) and a maintenance daily dosage. Comparison between 5 day weaning protocol reducing 20% of initial dosage + 5 days of placebo vs. 10 days weaning protocol reducing 10% of initial dosage. |
Additional dose of methadone equal to the same dose administered the day before or 0,025mg/kg of morphine IV or 0,05mg/kg of methadone incrementally every 30 minutes |
Neonatal Abstinence Score - Finnegan (NAS), modified Ramsay. |
5 days (n=16) vs. 10 days (n=21) |
No difference in incidence of abstinence between groups. |
Duration of mechanical ventilation, vasopressor therapy, pediatric intensive care unit (ICU) length of stay and pediatric risk of mortality scores did not differ between the two groups |
Steineck et al. (1616. Steineck KJ, Skoglund AK, Carlson MK, Gupta S. Evaluation of a pharmacist-managed methadone taper. Pediatr Crit Care Med. 2014;15(3):206-10.) |
Case - control (III) |
n=52, 1m – 16 yrs |
Weaning protocol based on the risk of development of abstinence by the duration of opioid and by the accumulate dose of fentanyl. Initial dose ranges from 0,05 to 0,2mg/ kg/dose every 8 or 6 hours with reduction rate of 10% to 33% per day. |
Additional dose of 0,05mg/kg of morphine IV every 2 hours if abstinence score between 9-11 or 0,1mg/kg if score ≥ 12 |
Modified Neonatal Abstinence Score - Finnegan (NAS) |
pharmaceutic guided protocol (n=20) vs. regular protocol (n=32) |
No difference in incidence of abstinence between groups. |
A shorter weaning time of methadone (24,7 days vs. 15 days; p=0,003) and shorter length of hospital stay (38%) in the intervention group |
Neunhoeffer et al. (44. Neunhoeffer F, Kumpf M, Renk H, Hanelt M, Berneck N, Bosk A, et al. Nurse-driven pediatric analgesia and sedation protocol reduces withdrawal symptoms in critically ill medical pediatric patients. Pediatric Anesth. 2015;25(8):786-794.) |
Clinical trial (IIB) |
n=337, 0-18 yrs |
Taper based on duration of opioid exposure: < 5 day - decrease of 50% of initial dose every 24hours; > 5 days - decrease of 10 to 20% every 24hours. |
Dose of morphine, fentanyl and midazolam is adjusted according to COMFOT-B and NISS scale. The reduction is suspended for 24 hours if SOS ≥ 4 |
COMFORT-B, Nurse Interpretation Sedation Scale (NISS), Sophia Observation Withdrawal (SOS). |
before protocol (n=165) vs. after protocol (n=172) |
Lower incidence of abstinence after implementation of protocol (12,8% vs. 23,6%, p=0,005) |
No difference in duration of mechanical ventilation, in days in ICU or total dosage of opioid. |
Best et al. (1717. Best KM, Asaro LA, Franck LS, Wypij D, Curley MA; Randomized Evaluation of Sedation Titration for Respiratory Failure Baseline Study Investigators. Patterns of sedation weaning in critically ill children recovering from acute respiratory failure. Pediatr Crit Care Med. 2016;17(1):19-29.) |
Prospective cohort (III) |
n=145, 2 wks – 17 yrs |
Group comparisons were made between patients with an intermittent weaning pattern, defined as a 20% or greater increase in daily opioid dose after the start of weaning, and the remaining patients defined as having a steady weaning pattern. |
Not specified in the study |
FLACC, Wong-Baker Faces, numerical scales to evaluate analgesia; State Behavior Scale; WAT-1. |
intermittent pattern (n=66) vs. steady pattern (n=79) |
Lower incidence of abstinence (WAT-1 ≥ 3) in the steady group: 46% vs. 85%, p<0,001. The tapering time of steady group was also shorter. |
Comparison between protocol group and non-protocol group: lower length of mechanical ventilation (5,9 vs. 9,1 days, p<0,001), lower length of ICU stay (9,3 days vs. 12,8 days, p<0,001) and lower length of hospital stay (14 days vs. 21,5 days, p<0,001). |
Robertson et al. (1414. Robertson RC, Darsey E, Fortenberry JD, Pettignano R, Hartley G. Evaluation of an opiate-weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care Med. 2000;1(2):119-23.) |
Clinical trial (III) |
n=20, 6 m – 18 yrs |
Weaning protocol based on duration of opioid exposure: 7 to 14 days: decrease of 20% every day (taper time of 5 days) > 14 day: decrease of 20% every 2 days (taper time of 10 days) |
Not specified in the study |
Scale based on signs and symptoms from Neonatal Abstinence Score. |
protocol (n=10) vs. non protocol (n=10) |
No difference in incidence of abstinence between groups. |
Lower weaning time in protocol group (9 days vs. 20 days, p<0,001). |