title: Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients.
abstract: BACKGROUND
  Short-acting opioids like remifentanil are suspected of an increased risk for tolerance, withdrawal and opioid-induced hyperalgesia (OIH). These potential adverse effects have never been investigated in neonates.
  
  
  OBJECTIVE
  To compare remifentanil and fentanyl concerning the incidence of tolerance, withdrawal and OIH.
  
  
  METHODS
  23 mechanically ventilated infants received up to 96 h either a remifentanil- or fentanyl-based analgesia and sedation regimen with low-dose midazolam. We compared the required opioid doses and the number of opioid dose adjustments. Following extubation, withdrawal symptoms were assessed by a modification of the Finnegan score. OIH was evaluated by the CHIPPS scale and by testing the threshold of the flexion withdrawal reflex with calibrated von Frey filaments.
  
  
  RESULTS
  Remifentanil had to be increased by 24% and fentanyl by 47% to keep the infants adequately sedated during mechanical ventilation. Following extubation, infants revealed no pronounced opioid withdrawal and low average Finnegan scores in both groups. Only 1 infant of the fentanyl group and 1 infant of the remifentanil group required methadone for treatment of withdrawal symptoms. Infants also revealed no signs of OIH and low CHIPPS scores in both groups. The median threshold of the flexion withdrawal reflex was 4.5 g (IQR = 2.3) in the fentanyl group and 2.7 g (IQR = 3.3) in the remifentanil group (p = 0.312), which is within the physiologic range of healthy infants.
  
  
  CONCLUSIONS
  Remifentanil does not seem to be associated with an increased risk for tolerance, withdrawal or OIH.
authors: Department of Neonatology, Children's Hospital, University Hospital of Bonn, Bonn, Germany. lars.welzing@ukb.uni-bonn.de
authors: Lars
authors: L
authors: Welzing
authors: Florian
authors: F
authors: Link
authors: Shino
authors: S
authors: Junghaenel
authors: Andre
authors: A
authors: Oberthuer
authors: Urs
authors: U
authors: Harnischmacher
authors: Hartmut
authors: H
authors: Stuetzer
authors: Bernhard
authors: B
authors: Roth
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D004361:Drug Tolerance; D005283:Fentanyl / Q000627:therapeutic use; D005865:Gestational Age; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000453:epidemiology; D006993:Hypnotics and Sedatives; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000628:therapy; D007363:Intensive Care Units, Neonatal; D015278:Intensive Care Units, Pediatric; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077208:Remifentanil; D012121:Respiration, Artificial; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology*
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D010880:Piperidines; D000077208:Remifentanil; D005283:Fentanyl