Unraveling the mysteries of sleep-disordered breathing in children.
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Biomedical subjects
Publications and source records attributed to Jerrold Lerman.
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BACKGROUND: To investigate dexmedetomidine in children, the authors performed an open-label study of the pharmacokinetics and pharmacodynamics of dexmedetomidine. METHODS: Thirty-six children were assigned to three groups; 24 received dexmedetomidine and 12 received no drug. Three doses of dexmedetomidine, 2, 4, and 6 microg x kg x h, were infused for 10 min. Cardiorespiratory responses and sedation were recorded for 24 h. Plasma concentrations of dexmedetomidine were collected for 24 h and analyzed. Pharmacokinetic variables were determined using nonlinear mixed effects modeling (NONMEM program). Cardiorespiratory responses were analyzed. RESULTS: Thirty-six children completed the study. There was an apparent difference in the pharmacokinetics between Canadian and South African children. The derived volumes and clearances in the Canadian children were V1 = 0.81 l/kg, V2 = 1.0 l/kg, Cl1 (systemic clearance) = 0.013 l x kg x min, Cl2 = 0.030 l x kg x min. The intersubject variabilities for V1, V2, and Cl1 were 45%, 38%, and 22%, respectively. Plasma concentrations in South African children were 29% less than in Canadian children. The volumes and clearances in the South African children were 29% larger. The terminal half-life was 110 min (1.8 h). Median absolute prediction error for the two-compartment mammillary model was 18%. Heart rate and systolic blood pressure decreased with time and with increasing doses of dexmedetomidine. Respiratory rate and oxygen saturation (in air) were maintained. Sedation was transient. CONCLUSION: The pharmacokinetics of dexmedetomidine in children are predictable with a terminal half-life of 1.8 h. Hemodynamic responses decreased with increasing doses of dexmedetomidine. Respiratory responses were maintained, whereas sedation was transient.
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BACKGROUND: Local anesthetics inhibit mediator and free radical release from polymorphonuclear granulocytes and migration to their site of action. In a recent study, lidocaine significantly improved the alveolar-arterial oxygen difference gradients (A-aDO2) after tracheal instillation of acid in rabbits. The purpose of the current study was to evaluate the effects of lidocaine and pulse-dose steroids on human breast milk (HBM)-induced lung injury in rabbits. METHODS: After Animal Care Committee approval, six adult rabbits were assigned to each of three treatments: control, lidocaine, and steroids. After induction of anesthesia and controlled ventilation, acidified HBM at pH 1.8 and volume 1.2 ml.kg(-1) was instilled into the trachea. Rabbits in the lidocaine group received lidocaine 2 mg.kg(-1) i.v. before tracheal instillation and then 2 mg.kg(-1).h(-1) i.v. continuously. Rabbits in the steroid group received 30 mg.kg(-1) methylprednisolone before tracheal instillation. A-aDO2, static compliance and blood for white cell count, and cytokine interleukin-8 (IL-8) concentration were obtained at baseline and at 1 and 4 h postinstillation. After 4 h, the rabbits were killed. The left upper lobe was isolated and excised to determine the wet/dry ratio. The right lung was lavaged with 30 ml normal saline to determine the white cell count and the concentrations of albumin and IL-8. Data were analyzed using one- or two-way anova with repeated measures and an Student-Newman-Keuls (SNK) posthoc test (P < 0.05). RESULTS: All rabbits completed the protocol. A-aDO2 and CO2 tensions increased significantly at 1 and 4 h compared with baseline, although there were no differences among the treatments (P < 0.05). Compliance in the control group decreased compared with lidocaine and steroids. CONCLUSION: We conclude that preemptive lidocaine and steroids attenuate in part HBM-induced lung injury in rabbits.
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BACKGROUND: The effects of low-flow anesthesia on the temperature and humidity of the inspired gas in infants during mechanical ventilation is unknown. This study was designed to evaluate the temperature and humidity of the inspired gas in infants using a pediatric circle absorber system with high and low fresh gas flow (HFGF and LFGF) anesthesia. METHODS: Twenty infants participated in this observational, sequential, cross-over study. Each infant was mechanically ventilated with a Kion Anesthesia Workstation, using a pediatric anesthesia circle circuit with both HFGF (6 l.min(-1)) and LFGF (0.6 l.min(-1)) technique. Airway temperature was recorded continuously at 16 sites throughout the breathing circuit. The relative humidity of the inspired gas was measured at the elbow connector adjacent to the CO2 sampling line. RESULTS: The mean airway temperatures of the inspired gas and the changes in mean airway temperatures throughout the breathing circuit during HFGF and LFGF did not differ significantly. The mean relative humidity of the inspired gas at steady state using a LFGF technique, 33.7 +/- 3.6%, was approximately threefold greater than it was with a HFGF technique, 11.9 +/- 5.1% (P < 0.05). CONCLUSIONS: Low-flow anesthesia with a pediatric circle system in infants neither increases the temperature of the inspired gas, nor achieves the minimum humidity of 50% reported to prevent ciliary damage, although the humidity during LFGF did increase threefold compared with HFGF. To maintain the temperature and humidity of the inspired gas during mechanical ventilation in infants, passive or active gas humidification should be used.
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BACKGROUND: Emergence delirium has been investigated in several clinical trials. However, no reliable and valid rating scale exists to measure this phenomenon in children. Therefore, the authors developed and evaluated the Pediatric Anesthesia Emergence Delirium (PAED) scale to measure emergence delirium in children. METHODS: A list of scale items that were statements describing the emergence behavior of children was compiled, and the items were evaluated for content validity and statistical significance. Items that satisfied these evaluations comprised the PAED scale. Each item was scored from 1 to 4 (with reverse scoring where applicable), and the scores were summed to obtain a total scale score. The degree of emergence delirium varied directly with the total score. Fifty children were enrolled to determine the reliability and validity of the PAED scale. Scale validity was evaluated using five hypotheses: The PAED scale scores correlated negatively with age and time to awakening and positively with clinical judgment scores and Post Hospital Behavior Questionnaire scores, and were greater after sevoflurane than after halothane. The sensitivity of the scale was also determined. RESULTS: Five of 27 items that satisfied the content validity and statistical analysis became the PAED scale: (1) The child makes eye contact with the caregiver, (2) the child's actions are purposeful, (3) the child is aware of his/her surroundings, (4) the child is restless, and (5) the child is inconsolable. The internal consistency of the PAED scale was 0.89, and the reliability was 0.84 (95% confidence interval, 0.76-0.90). Three hypotheses supported the validity of the scale: The scores correlated negatively with age (r = -0.31, P <0.04) and time to awakening (r = -0.5, P <0.001) and were greater after sevoflurane anesthesia than halothane (P <0.008). The sensitivity was 0.64. CONCLUSIONS: These results support the reliability and validity of the PAED scale.
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BACKGROUND: Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as bupivacaine but less toxic. Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children. METHODS: After Research Ethics Board approval and informed written consent, 120 healthy children aged 6 months to 12 yr who were scheduled to undergo urologic or abdominal surgery were randomized in a double-blinded and concealed manner to receive one of four epidural solutions as a continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml fentanyl. After induction of anesthesia and tracheal intubation, a lumbar epidural catheter was sited, a loading dose was administered (0.75 ml/kg levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary endpoint was the need for rescue analgesia (morphine) in the first 10 h after surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous blood was collected from 18 children to determine the plasma concentrations of levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after the start of the epidural infusion. RESULTS: Of the 114 children who were analyzed for intention to treat, a similar number of children in each group reached the 10-h mark. The time to the first dose of morphine in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 +/- 0.11 mug/ml in the 0.125% group and 0.48 +/- 0.12 mug/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 +/- 0.11 ng/ml by 24 h. CONCLUSION: We conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children when infused at a rate of 0.3 ml. kg-1. h-1. The plasma concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 mug/ml) at the end of a 24-h infusion are low.
Pain has been an understated concern in infants and children. Failure to recognize pain in the past has resulted in undue suffering by infants and children of all ages, but with the introduction of instruments to measure pain and a widespread appreciation of the severity of this problem in this age group, pain is rapidly coming under control. Novel concepts in both old and new analgesics have created safe and effective pain management strategies for infants and children. This review examines three analgesics and their potential roles in infants and children: cyclo-oxygenase (COX)-2 inhibitors, alpha 2-agonists and opioids.
BACKGROUND: Preparation of anesthetic machines for use with malignant hyperthermia-susceptible (MHS) patients requires that the machines be flushed with clean fresh gas. We investigated the washout of inhalational anesthetics from the KION anesthetic machine. METHODS: In part 1, halothane was circulated through KION anesthetic machines for either 2 or 12 h using a test lung. The times to washout halothane (to 10 parts per million [ppm]) first, from the internal circuitry and second, from the ventilator-patient cassette (without the carbon dioxide absorber) were determined at 5 and 10 l/min fresh gas flow (FGF). In part 2, the rates of washout of halothane or isoflurane from either the KION or Ohmeda Excel 210 machines were compared. The effluent gases were analyzed using calibrated Datex Capnomac Ultima (Helsinki, Finland) and a Miran LB2 Portable Ambient Air Analyzer (Foxboro, Norwalk, CT). RESULTS: Halothane was washed out of the internal circuitry of the KION within 5 min at 10 l/min FGF. Halothane was eliminated from the ventilator-patient cassette in 22 min at the same FGF. The times to reach 10 ppm concentration of halothane and isoflurane in the KION at 10 l/min FGF, 23 to 25 min, was four-fold greater than those in the Ohmeda Excel 210, 6 min. CONCLUSIONS: To prepare the KION anesthetic machine for MHS patients, the machine without the carbon dioxide absorber must be flushed with 10 l/min FGF for at least 25 min to achieve 10 ppm anesthetic concentration. This FGF should be maintained throughout the anesthetic to avoid increases in anesthetic concentration in the FGF.