Amirnovin et al.,(88 Amirnovin R, Sanchez-Pinto LN, Okuhara C, Lieu P, Koh JY, Rodgers JW, et al. Implementation of a risk-stratified opioid and benzodiazepine weaning protocol in a pediatric cardiac ICU. Pediatr Crit Care Med. 2018;19(11):1024-32.) United States |
Foresight before and after intervention |
Children admitted to the pediatric cardiac ICU who received opioid infusions ≥7 days |
119 |
< 21 years (mean 10 months) |
Control: weaning at medical discretion Intervention: protocolized weaning |
Bowens et al.,(1919 Bowens CD, Thompson JA, Thompson MT, Breitzka RL, Thompson DG, Sheeran PW. A trial of methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged sedative infusions. Pediatr Crit Care Med. 2011;12(5):504-11.) United States |
Prospective, double-blind, randomized |
Children admitted to the pediatric ICU with ≥ 5 days of fentanyl infusion |
68 |
> 28 days to < 18 years (mean 4.4 months) |
Control: protocolized management of WS in “low doses” (according to weight) of methadone Intervention: protocolized management of WS using “high-dose” methadone (according to fentanyl infusion rate) |
Garisto et al.,(2020 Garisto C, Ricci Z, Tofani L, Benegni S, Pezzella C, Cogo P. Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial. Minerva Anestesiol. 2018;84(9):1053-62.) Italy |
Randomized clinical trial |
Children admitted to the pediatric ICU with congenital heart disease |
48 |
> 28 days to < 24 months (mean 5.5 months) |
Control: use of opioids and benzodiazepines alone Intervention: use of benzodiazepines and opioids with dexmedetomidine |
Hünseler et al.,(2121 Hünseler C, Balling G, Röhlig C, Blickheuser R, Trieschmann U, Lieser U, et al. Continuous infusion of clonidine in ventilated newborns and infants: a randomized controlled trial. Pediatr Crit Care Med. 2014;15(6):511-22.) Germany |
Prospective, double-blind, randomized controlled trial |
Children admitted to the pediatric ICU on MV for more than 3 days and on midazolam and fentanyl |
219 |
NB with GA > 37 weeks up to 2 years (mean 10 months) |
Control: patients received clonidine infusion Intervention: patients received a placebo infusion |
Tiacharoen et al.,(2222 Tiacharoen D, Lertbunrian R, Veawpanich J, Suppalarkbunlue N, Anantasit N. Protocolized sedative weaning vs usual care in pediatric critically ill patients: a pilot randomized controlled trial. Indian J Crit Care Med. 2020;24(6):451-8.) Thailand |
Open, randomized and controlled study |
Children who received intravenous sedatives or analgesics for ≥ 5 days |
30 |
> 1 month and < 18 years (mean 20.76 months) |
Control: weaning at medical discretion Intervention: weaning was protocolized through risk assessment for the development of WS |
Gaillard-Le Roux et al.,(2323 Gaillard-Le Roux B, Liet JM, Bourgoin P, Legrand A, Roze JC, Joram N. Implementation of a nurse-driven sedation protocol in a PICU decreases daily doses of midazolam. Pediatr Crit Care Med. 2017;18(1): e9-17.) França |
Prospective, before and after |
Children admitted to the pediatric ICU |
194 |
> 28 days to < 18 years (mean 6.6 months) |
Control: weaning at medical discretion |
Sanchez-Pinto et al.,(2424 Sanchez-Pinto LN, Nelson LP, Lieu P, Koh JY, Rodgers JW, Larson KA, et al. Implementation of a risk-stratified opioid weaning protocol in a pediatric intensive care unit. J Crit Care. 2018;43:214-9.) Estados Unidos |
Prospective pre- and post-intervention |
Children admitted to the pediatric ICU who received scheduled opioids for ≥ 7 days |
107 |
< 21 years (mean 26.4 months) |
Control: weaning at medical discretion Intervention: protocolized weaning |
Geven et al.,(2525 Geven BM, Maaskant JM, Ward CS, van Woensel JB. Dexmedetomidine and iatrogenic withdrawal syndrome in critically ill children. Crit Care Nurse. 2021;41(1):e17-23.) Holanda |
Retrospective observational |
Children admitted to the pediatric ICU who used benzodiazepines and opioids for 48 hours continuously |
102 |
< 18 years (mean 14 months) |
Observation of patients weaned on dexmedetomidine after use of benzodiazepines and opioids |
Sperotto F, et al.,(2626 Sperotto F, Mondardini MC, Dell’Oste C, Vitale F, Ferrario S, Lapi M, Ferrero F, Dusio MP, Rossetti E, Daverio M, Amigoni A; Pediatric Neurological Protection and Drugs (PeNPAD) Study Group of the Italian Society of Neonatal and Pediatric Anesthesia and Intensive Care (SARNePI). Efficacy and safety of dexmedetomidine for prolonged sedation in the PICU: a prospective multicenter study (PROSDEX). Pediatr Crit Care Med. 2020;21(7):625-36.) Italia |
Observational prospective |
Patients < 18 years of age who received dexmedetomidine for a period greater than or equal to 24 hours |
163 |
< 18 years (mean 13 months) |
Observation of patients before and after 24 hours of dexmedetomidine infusion |
van der Vossen et al.,(2727 van der Vossen AC, van Nuland M, Ista EG, Wildt SN, Hanff LM. Oral lorazepam can be substituted for intravenous midazolam when weaning paediatric intensive care patients off sedation. Acta Paediatr. 2018;107(9):1594-600.) Holanda |
Retrospective cohort |
Children admitted to the pediatric ICU |
73 |
< 18 years (mean 63.3 months) |
Control: evaluation of patients before conversion from midazolam to lorazepam Intervention: evaluation of patients 48 hours after conversion |
Sanavia et al,(2828 Sanavia E, Mencía S, Lafever SN, Solana MJ, Garcia M, López-Herce J. Sedative and analgesic drug rotation protocol in critically ill children with prolonged sedation: evaluation of implementation and efficacy to reduce withdrawal syndrome. Pediatr Crit Care Med. 2019;20(12):1111-7.) Espanha |
Observational prospective |
Children admitted to the pediatric ICU who received continuous infusions of sedatives and analgesics for > 4 days |
100 |
> 1 month to 16 years (mean 8 months) |
Observation of patients using medication rotation protocol |
Berrens et al.,(2929 Berrens ZJ, Sauro AL, Tillman EM. Prevention of withdrawal in pediatric patients receiving long-term dexmedetomidine infusions. J Pediatr Pharmacol Ther. 2021;26(1):81-6.) Estados Unidos |
Retrospective study |
Children admitted to the pediatric ICU |
50 |
> 1 month to < 18 years (mean 24 months) |
Observation of patients weaned on clonidine compared to patients weaned on dexmedetomidine alone |