Remifentanil-induced tolerance, withdrawal or hyperalgesia in infants: a randomized controlled trial. RAPIP trial: remifentanil-based analgesia and sedation of paediatric intensive care patients.

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. OBJECTIVES: 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.

Fast diastolic swinging motion of the mitral valve as a clinical marker of familial hypertrophic cardiomyopathy in genetically affected young children without left ventricular hypertrophy: a new role for noninvasive imaging?

Structural mitral valve (MV) abnormalities are common in patients with hypertrophic cardiomyopathy (HCM). This is the first report demonstrating MV abnormalities in very young children as the sole overt clinical feature of a known HCM-causing sarcomere protein gene mutation. Due to MV leaflet elongation, we also noticed a typical fast diastolic swinging motion of the MV in our patients. This novel echocardiographic feature may be used as a clinical marker of HCM disease in the absence of left ventricular hypertrophy.

Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of mechanically ventilated neonates and young infants: a randomized controlled trial.

PURPOSE: Common opioids for analgesia and sedation of mechanically ventilated infants may tend to accumulate and cause prolonged sedation with an unpredictable extubation time. Remifentanil is a promising option due to its unique pharmacokinetic properties, which seem to be valid in adults as well as in infants. METHODS: In this double-blind, randomized, controlled trial mechanically ventilated neonates and young infants (<60 days) received either a remifentanil or fentanyl-based analgesia and sedation regimen with low dose midazolam. The primary endpoint of the trial was the extubation time following discontinuation of the opioid infusion. Secondary endpoints included efficacy and safety aspects. RESULTS: Between November 2006 and March 2010, we screened 431 mechanically ventilated infants for eligibility. The intention to treat group included 23 infants who were assigned to receive either remifentanil (n = 11) or fentanyl (n = 12). Although this was designed as a pilot study, median extubation time was significantly shorter in the remifentanil group (80.0 min, IQR = 15.0-165.0) compared to the fentanyl group (782.5 min, IQR = 250.8-1,875.0) (p = 0.005). Remifentanil and fentanyl provided comparable efficacy with more than two-thirds of the measurements indicating optimal analgesia and sedation (66.4 and 70.2 %, respectively; p = 0.743). Overall, both groups had good hemodynamic stability and a comparably low incidence of adverse events. CONCLUSIONS: As neonates and young infants have a decreased metabolism of common opioids like fentanyl and are more prone to respiratory depression, remifentanil could be the ideal opioid for analgesia and sedation of mechanically ventilated infants.

Massive macroglossia after palatoplasty: case report and review of the literature.

UNLABELLED: Cleft palates are among the most common birth defects. Serious complications in perioperative airway management after palatoplasty are rare and mostly described in children with preexisting compromise of airway due to craniofacial anomalies. A very uncommon but typical and frightening complication is postoperative extreme, very rapid emergence, and life-threatening macroglossia. While macroglossia usually has its peak within 24-48 h after palatoplasty and resolves spontaneously, we report a patient with massive lingual swelling with complete obstruction of the upper airway on the fifth postoperative day requiring tracheotomy. Swelling only resolved after removing the endotracheal tube after tracheotomy. Next to the description of our case, we discuss standard care procedure in perioperative management of patients with cleft palate to prevent this life-threatening complication after palatoplasty. CONCLUSION: Macroglossia can occur even 3-5 days after surgery and can be maintained by the pressure of the endotracheal tube to the tongue ground. Knowledge and avoidance of these risk factors are as important as early treatment of respiratory compromise.

Remifentanil and propofol for weaning of mechanically ventilated pediatric intensive care patients.

Mechanically ventilated pediatric intensive care patients usually receive an analgesic and sedative to keep them comfortable and safe. However, common drugs like fentanyl and midazolam have a long context sensitive half time, resulting in prolonged sedation and an unpredictable extubation time. Children often awake slowly and struggle against the respirator, although their respiratory drive and their airway reflexes are not yet sufficient for extubation. In this pilot study, we replaced fentanyl and midazolam at the final phase of the weaning process with remifentanil and propofol. Twenty-three children aged 3 months-10 years were enrolled. Remifentanil and propofol revealed throughout excellent or good weaning conditions with rapid transition from hypnosis to the development of regular spontaneous breathing, airway protective reflexes, and an appropriate level of alertness. Extubation time following discontinuation of the remifentanil and propofol infusion was only 24 ± 20 min (5-80 min). We conclude that the combination of remifentanil and propofol is a promising option to improve the weaning conditions of pediatric intensive care patients. Randomized controlled trials are needed to compare remifentanil and propofol with conventional weaning protocols.