A multicenter, randomized, open-label, active-comparator trial to determine the efficacy, safety, and pharmacokinetics of intravenous ibuprofen for treatment of fever in hospitalized pediatric patients.

BACKGROUND: Oral antipyretics are commonly used to treat pediatric patients who develop fevers. However, patients presenting to the emergency department or undergoing surgery are frequently unable to tolerate oral antipyretics. Rectal formulations are available; however, this route of administration is unpredictable. The main objectives of this randomized controlled study was to evaluate the efficacy and safety of single or multiple doses of intravenous ibuprofen to acetaminophen (oral or suppository) in pediatric patients with fever and to assess plasma ibuprofen concentrations. METHODS: This multi-center study was conducted in hospitalized patients, ≤ 16 years, with a new onset of fever ≥ 38.3°C. Patients were randomly assigned to receive either 10 mg/kg intravenous ibuprofen or acetaminophen. Study drug was administered at hour 0, and thereafter every 4 h as needed, up to 5 days. The primary outcome was to evaluate the effect of a single dose of intravenous ibuprofen compared to acetaminophen in reducing temperature in the first 2 h after administration. Data were compared using an analysis of variance model for continuous measurements and Cochran-Mantel-Haenszel test of general association for categorical data. A two-sided testing was used and a p-value ≤ 0.05 was considered significant. RESULTS: A total of 103 patients received study medication. Intravenous ibuprofen resulted in a greater reduction in temperature as measured by the area under the change from baseline at 2 h (p = 0.005) and 4 h (<0.001); in a greater reduction in change from baseline temperature compared to treatment with acetaminophen, and it reduced fever throughout a 24 h dosing period. There were no differences in safety parameters or serious adverse events. CONCLUSIONS: A single 10 mg/kg dose of intravenous ibuprofen provided a significant reduction of temperature for febrile pediatric patients compared to those that received 10 mg/kg acetaminophen at 2 h and 4 h post-treatment. A reduction in temperature was also demonstrated over 24 h; however the reduction was not considered statically significant. Intravenous ibuprofen provides an effective option for reducing fever in hospitalized pediatric patients. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov on 26 October 2009, Study Identifier: NCT01002573.

Airway responses to desflurane during maintenance of anesthesia and recovery in children with laryngeal mask airways.

BACKGROUND: We sought to characterize the airway responses to desflurane during maintenance of and emergence from anesthesia in children whose airways were supported with laryngeal mask airways (LMAs). METHODS/MATERIALS: Four hundred healthy children were randomized in a 3 : 1 ratio to either desflurane or isoflurane (reference group) during anesthetic maintenance. After induction of anesthesia, anesthesia was maintained with the designated anesthetic. The investigator chose the airway (LMA and facemask), ventilation strategy and when to remove the LMA. The incidence of airway events during maintenance, emergence and recovery was recorded. RESULTS: Ninety percent of children received LMAs. The frequency of major airway events after desflurane (9%) was similar to that after isoflurane (4%) (number needed to harm [NNH] 20), although the frequency of major events after the LMA was removed during deep desflurane anesthesia (15%) was greater than during awake removal (5%) (NNH 10) (P < 0.006) and during deep isoflurane removal (2%) (NNH 8) (P < 0.03). The frequency of airway events of any severity after desflurane was greater than that after isoflurane (39% vs 27%) (P < 0.05). The frequencies of laryngospasm and coughing of any severity after desflurane were greater than those after isoflurane (13% vs 5% and 26% vs 14%, respectively) (P < 0.05). CONCLUSIONS: When an LMA is used during desflurane anesthesia in children, fewer airway events occur when it is removed when the child is awake. Although the time to discharge from recovery was not delayed and no child required overnight admission, caution should be exercised when using an LMA in children who are anesthetized with desflurane.

Presurgical fentanyl vs caudal block and the incidence of adverse respiratory events in children after orchidopexy.

BACKGROUND: There is controversy about the etiology of early postoperative hypoxemia. Age, weight, intubation, surgical procedure, use of muscle relaxants, and/or administration of opioids may affect the incidence of early postoperative hypoxemia. In this prospective, randomized, and single-blinded study, we evaluated whether the administration of caudal analgesia vs i.v. fentanyl affected the number of children who develop postextubation adverse upper airway respiratory events, (upper airway obstruction, laryngospasm) and/or early postoperative hypoxemia. METHODS/MATERIALS: Institutional approval and written parental informed consents were obtained. Thirty-eight healthy outpatient boys, aged 1-6 years, scheduled for elective orchidopexy were randomized to receive pain relief either with a presurgical caudal block or by i.v. fentanyl. The primary outcome of the study was the number of children who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia. RESULTS: The number of boys who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia in the caudal group was less compared with those in the fentanyl group (P = 0.04). CONCLUSIONS: Compared to fentanyl, placement of a presurgical caudal block in boys scheduled for orchidopexy was associated with a lower incidence of postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia.

Caffeine in children with obstructive sleep apnea.

BACKGROUND: Children with obstructive sleep apnea (OSA) have a higher rate of adverse post-extubation respiratory events, such as laryngospasm, upper airway obstruction, apnea, desaturation and/or need for re-intubation. They are overly sensitive to sedatives and narcotics. Although the etiology of OSA is primarily obstruction (mechanical or neuromuscular), a central element may contribute to OSA. Caffeine citrate has been shown to be effective in treating apnea of prematurity. This study evaluated whether the administration of caffeine benzoate to children with OSA decreases the number of children who experience adverse post-extubation respiratory events. METHODS: In a randomized, double-blind and placebo-controlled study, children with OSA scheduled for adenotonsillectomy (T&A) received either caffeine benzoate, 20 mg/kg IV, (caffeine group, n = 36) or saline (placebo group, n = 36). The primary outcome evaluated the number of children who developed adverse post-extubation respiratory events, and the secondary outcome was the incidence of those events. RESULTS: The results demonstrated the two groups differed in the number of children who developed adverse post-extubation respiratory events (p = 0.032). The overall incidence of adverse postoperative respiratory events was less in the caffeine group than the placebo group (p = 0.0196). CONCLUSION: In children with OSA scheduled for T&A, administration of caffeine benzoate, 20 mg/kg IV, decreased the number of children who developed adverse post-extubation respiratory events and decreased the overall incidence of adverse post-extubation respiratory events. PACU duration, hospital discharge time and postoperative delirium did not differ between groups.

Presurgical caudal block attenuates stress response in children.

BACKGROUND: Our aim was to determine if the anesthesia technique for pain relief in children affects the stress response after minor surgery. A rise in blood glucose reflects stress-related effects in children who do not receive glucose perioperatively. METHODS: Twenty-eight children, ages 17-81 mos, undergoing elective urologic procedures, were enrolled. For pain relief, patients received presurgical caudal block (group 1), intravenous narcotics (group 2), or postsurgical caudal block (group 3). Blood samples were analyzed for glucose concentrations immediately after induction of anesthesia at baseline, 15 min after surgical incision (second sample), and 30 min after end of surgery (third sample). RESULTS: In group 1 there was no change in glucose concentration in the second or third samples compared to baseline, while in group 3 there were significant increases in those samples, and in group 2 there was a significant increase in the second sample compared to baseline. Children in group 1 required significantly fewer narcotics in the postanesthesia care unit (PACU), and those in group 2 had significantly longer PACU and hospital durations. CONCLUSIONS: Presurgical caudal analgesia attenuates the stress response of anesthesia and surgery and decreases postoperative narcotic use while narcotics prolong PACU and discharge times.

Regional analgesia combined with avoidance of narcotics may reduce the incidence of postoperative vomiting in children.

BACKGROUND: The anesthesia literature cites a high incidence of postoperative vomiting (POV) after pediatric ochidopexy and hernia repair (34-50%) and after penile procedures (37-49%). We hypothesized that regional analgesia combined with avoidance of narcotics administered to children scheduled for lower abdominal or urologic procedures may be associated with a lower incidence of POV. The aim of this prospective study was to 1) assess the incidence of POV in children in the hospital and during a 24-h post-anesthesia study period, and 2) evaluate the effect of age on POV. METHODS: After obtaining institutional and parental consent, 110 pediatric outpatients, 1-12 yr old, ASA physical status I or II, scheduled for elective outpatient urologic or lower abdominal procedures, were enrolled. Children were fasting and premedicated with midazolam, 0.5 mg/kg p.o. They received a combined light general anesthesia and a presurgical caudal block. Anesthesia was induced via a mask and consisted of halothane and nitrous oxide in oxygen. For the caudal block 1 ml/kg of 0.25% bupivacaine or 0.2% ropivacaine were used to provide intra- and postoperative pain relief. No prophylactic antiemetics were administered. RESULTS: All caudal blocks provided adequate intraoperative pain relief. The incidence of POV was low, 12% at the hospital, 13% for the 24-h study period, and was not affected by age. CONCLUSIONS: We concluded that regional analgesia combined with the avoidance of narcotics administered to children scheduled for elective urologic or lower abdominal procedures, is associated with a lower incidence of POV and that age did not affect the incidence of POV.

A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.

UNLABELLED: We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). IMPLICATIONS: This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.

A paediatric trial comparing midazolam/Syrpalta mixture with premixed midazolam syrup (Roche).

BACKGROUND: The bitter taste of midazolam is more acceptable to children when the drug is mixed with fruit juice or syrup. We use a thick grape syrup (Syrpalta), and children are sedated in 10-15 min. A premixed cherry-flavoured midazolam solution (Roche), 2 mg.ml (-1), is currently available. It has been our impression that the premixed midazolam has a slower onset of action. Our aim was to evaluate the effects of the midazolam mixtures (midazolam 0.5 mg.kg (-1), 2 mg.ml (-1)) on children's anxiety, sedation, separation anxiety, mask acceptance, and recovery time. METHODS: Seventy-six healthy children, 1-4 years of age, scheduled for elective placement of ear tubes, were enrolled. The trial was double-blinded and randomized. For premedication, one group received the premixed midazolam, and a second group received the midazolam/Syrpalta mixture. An independent blinded observer evaluated the children, using anxiety and sedation scales at baseline, at 5, 10 and 15 min and at parental separation. Mask acceptance and awakening time were evaluated. RESULTS: Children who received the midazolam/Syrpalta mixture had less anxiety at 15 min (P = 0.046) and at parental separation (P < 0.001) than those who received the premixed midazolam solution. Mask acceptance was not different. CONCLUSIONS: We concluded that the midazolam/Syrpalta mixture has a faster onset of action than the premixed midazolam solution.