Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery.

BACKGROUND: Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery. METHODS: Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. RESULTS: Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. CONCLUSIONS: EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Preoperative oral dextromethorphan does not reduce pain or analgesic consumption in children after adenotonsillectomy.

UNLABELLED: In this randomized, double-blinded, placebo-controlled, prospective study, we evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o. 1 h before adenotonsillectomy in 57 children 6-12 yr of age. Anesthetic management was standardized. Morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. were administered after anesthetic induction but before the start of surgery. A 4-point behavioral score (1 = asleep, 2 = awake and calm, 3 = awake and crying, 4 = thrashing) was recorded on admission to and discharge from the postanesthesia care unit (PACU). In the PACU, pain was assessed with Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and recorded every 15 min until the patient was transferred to the day surgery unit (DSU). In the DSU, patients rated their pain using a 10-cm baseline 0-10 visual analog pain scale (VAS) every 30 min until they were discharged home. A 24-h VAS was obtained by phone interview, and parental satisfaction was scored (yes/no) regarding their child's postoperative analgesia. Morphine 0.025 mg/kg i.v. was administered to children with CHEOPS score >6, who verbalized pain, or who were crying in any consecutive 5-min observation periods in the PACU. Total morphine consumption was recorded. The study groups were comparable with respect to demographic variables. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, CHEOPS, behavior scores, VAS, or parental satisfaction. IMPLICATIONS: Premedication with dextromethorphan 0.5 or 1.0 mg/kg p.o. does not improve postoperative analgesia in school-aged children who receive preemptive morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. during nitrous oxide and desflurane anesthesia for adenotonsillectomy.

A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis.

UNLABELLED: This prospective, nonrandomized, observational study of 76 infants with pyloric stenosis was conducted at an academic children's hospital and compared awake versus paralyzed tracheal intubation in terms of successful first attempt rate, intubation time, heart rate (HR) and arterial hemoglobin oxygen saturation (SpO2) changes, and complications. Three groups were determined by intubation method: awake (A) with an oxygen-insufflating laryngoscope, after rapid-sequence induction (R), or after modified rapid-sequence induction (M) including ventilation through cricoid pressure. Successful first attempt intubation rate was 64% for Group A versus 87% for paralyzed Groups R and M (P = 0.028). Median intubation time was 63 s in Group A versus 34 s in Groups R and M (P = 0.004). Transient, mild decreases in mean HR and SpO2 and incidences of significant bradycardia and decreased SpO2 did not vary by group. Complications, including bronchial or esophageal intubation, emesis, and oropharyngeal trauma, were few. Senior anesthesiologists intervened in four tracheal intubations. We advocate anesthetized, paralyzed tracheal intubation because struggling with conscious infants takes longer, often requires multiple attempts, and prevents neither bradycardia nor decreased SpO2. After induction, additional mask ventilation with O2 confers no advantage over immediate tracheal intubation in preserving SpO2. IMPLICATIONS: In our children's hospital, awake tracheal intubation was not superior to anesthetized, paralyzed intubation in maintaining adequate oxygenation and heart rate or in reducing complications, and should be abandoned in favor of the latter technique for routine anesthetic management of otherwise healthy infants with pyloric stenosis.

Endoscopic findings in hypertrophic pyloric stenosis: appearance in classic and evolving disease.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is the most common abdominal surgical disorder in infants. Although the majority of cases are diagnosed by ultrasound, equivocal cases may require endoscopy. This study was performed to assess the various endoscopic appearances of HPS in infants. METHODS: A prospective study comparing the endoscopic appearance of the antrum and pylorus of 18 children with HPS to 21 children in a normal control group. RESULTS: Antral or pyloric mucosal hypertrophy was visualized endoscopically in all 18 study patients. The degree of mucosal thickening varied depending on the age of presentation and duration of symptoms. Antral fold hypertrophy was first noted at 10 days of age, and in the oldest patient (4 months of age) a pyloric mass was noted. By comparison, 21 control infants had no evidence of antral or pyloric narrowing or mucosal thickening. CONCLUSIONS: Upper endoscopy can be a valuable adjunctive diagnostic tool in select cases of HPS when imaging tests are inconclusive or when infants present with clinical symptoms outside the typical age-time frame for HPS. Because HPS may evolve over time, it is important that the endoscopist recognize the different appearances of HPS.

Gastric fluid volume in infants for pyloromyotomy.

PURPOSE: To quantify gastric fluid volumes in infants with pyloric stenosis presenting for pyloromyotomy and to demonstrate endoscopically the efficacy of blind aspiration for gastric fluid recovery. We hypothesized that previous diagnostic contrast studies, preoperative nasogastric suction, and fasting interval would not affect these volumes. METHODS: Seventy-five infants scheduled for pyloromyotomy were given atropine before induction of anaesthesia. For those who had undergone preoperative nasogastric suction, the nasogastric tube was aspirated and removed. A 14 F multiorificed orogastric catheter was blindly passed to aspirate gastric fluid for measurement. Following tracheal intubation, 15/75 subjects underwent gastroscopy to measure residual gastric fluid. RESULTS: Gastric fluid volume removed by blind aspiration averaged 4.8 +/- 4.3 ml.kg-1 with 83% of patients having > 1.25 ml.kg-1. Although 14 of the 15 patients evaluated by endoscope had < or = 1 ml residual gastric fluid, one had 1.8 ml.kg-1. Recovery of total gastric fluid volume by blind aspiration averaged 96 +/- 7%. The large gastric fluid volumes were independent of a history of barium study, preoperative nasogastric suction, and fasting interval. CONCLUSION: Infants with pyloric stenosis have large gastric fluid volumes which are not substantially reduced by preoperative nasogastric suction. Blind aspiration of gastric contents prior to induction of anaesthesia provides a reliable estimate of total gastric fluid for most of these infants, although the occasional infant may retain a small amount of gastric fluid. The clinical importance of such a residual volume is uncertain.

Gastric fluid measurement by blind aspiration in paediatric patients: a gastroscopic evaluation.

PURPOSE: Numerous investigators have estimated gastric fluid volume using blind aspiration through multi-orificed catheters, but none have confirmed the validity of this technique in infants and children. We sought to validate the accuracy of this technique in a fasted paediatric population by using gastroscopy. Data from several studies were then combined to generate a gastric fluid volume frequency distribution for healthy paediatric patients fasted for surgery. METHODS: This is a prospective study of 17 patients aged six months to 11 yr who underwent elective upper endoscopy at a paediatric teaching hospital. Gastric contents were aspirated blindly with a syringe and a 16 or 18F multi-orificed orogastric tube, and the volume of gastric contents removed in the supine and decubitus positions was measured. Residual gastric fluid was aspirated using an endoscope. Data from 611 infants and children enrolled in previously published studies utilizing the same blind aspiration technique were pooled and a gastric fluid volume frequency distribution was created. RESULTS: Blind aspiration removed 97 +/- 8% of the total gastric fluid volume. In 661 children presenting for elective surgery, the gastric fluid volume was 0.40 +/- 0.45 ml.kg-1. Median volume was 0.27 ml.kg-1, with the 95%ile at 1.25 ml.kg-1 and an upper limit of 4.1 ml.kg-1. CONCLUSION: Blind aspiration of gastric contents accurately estimates gastric fluid volume for paediatric patients fasted for surgery. Population estimates for gastric fluid volume in otherwise healthy fasted paediatric patients are shown.

Oral and nasotracheal light wand guided intubation after failed fibreoptic bronchoscopy.

Fibreoptic bronchoscopic guided tracheal intubation is often the first choice for clinicians familiar with the technique, when faced with a patient in whom tracheal intubation presents known or possible difficulties. Regardless of the technique chosen, anticipated and unanticipated problems may arise. We report three patients with known difficult airways that illustrate the utility of light wand guided oral and nasotracheal intubation when tracheal intubation with fibreoptic bronchoscopy proved impossible.

A simple homemade lighted stylet for neonates and infants: a description and case report of its use in an infant with the Pierre Robin anomalad.

The glossoptosis and micrognathia associated with Pierre Robin anomalad can make tracheal intubation by conventional laryngoscopy quite difficult. Lighted stylets may be helpful in the successful intubation of infants with this anomalad, but those currently available that are small enough to accommodate 3.0 mm ID tracheal tubes have two major drawbacks limiting their utility: an insufficiently rigid stylet component and a nonadjustable, overly bright light. We describe a lighted stylet that can be easily assembled in the operating room which overcomes these problems and allowed us to successfully intubate a six-day-old with severe Pierre Robin anomalad.

Intraoperative latex anaphylaxis in children: classification and prophylaxis of patients at risk.

Over a 3-year period, in 36,075 general anesthetic anesthesia procedures done at our institution, 21 patients had type I (anaphylactic) intraoperative reactions to latex (phase 1). We subsequently established a system for classification of at-risk patients with a corresponding regimen for prophylaxis used prospectively between January 1992 and July 1994 (phase II). Three groups of patients at risk for type I hypersensitivity reaction were identified, and a regimen for prophylaxis developed (based in part on protocols used in preparing patients who are allergic to radiocontrast media). Since using this protocol, the incidence of intraoperative anaphylaxis has decreased. During phase 2, 34,513 patients received a general anesthetic in the operating room, and there have been three cases of suspected intraoperative latex anaphylaxis; two of these three patients did not meet any of the risk criteria and therefore did not receive preoperative prophylaxis or avoidance of latex. Of these 34,513 patients, 86 at-risk patients received prophylaxis. A prospective study is needed to determine whether the pharmacologic prophylaxis is needed in addition to a latex-free environment.

Do children who experience laryngospasm have an increased risk of upper respiratory tract infection?

BACKGROUND: Laryngospasm is the most frequently reported respiratory complication associated with upper respiratory infection and general anesthesia in retrospective studies, but prospective studies have failed to demonstrate any increase in risk. METHODS: A case-control study was performed to examine whether children with laryngospasm were more likely to have an upper respiratory infection on the day of surgery. The parents of all patients (N = 15,183) who were admitted through the day surgery unit were asked if their child had an active or recent (within 2 weeks of surgery) upper respiratory infection and were questioned about specific signs and symptoms to determine if the child met Tait and Knight's definition of an upper respiratory infection. Control subjects were randomly selected from patients whose surgery had occurred within 1 day of the laryngospasm event. RESULTS: Patients who developed laryngospasm (N = 123) were 2.05 times (95% confidence interval 1.21-3.45) more likely to have an active upper respiratory infection as defined by their parents than the 492 patients in the control group (P < or = 0.01). The development of laryngospasm was not related to Tait and Knight's definition for an upper respiratory infection or to recent upper respiratory infection. Children with laryngospasm were more likely to be younger (odds ratio = 0.92, 95% confidence interval 0.87-0.99), to be scheduled for airway surgery (odds ratio = 2.08, 95% confidence interval 1.21-3.59), and to have their anesthesia supervised by a less experienced anesthesiologist (odds ratio = 1.69, 95% confidence interval 1.04-2.7) than children in the control group. CONCLUSION: Laryngospasm was more likely to occur in children with an active upper respiratory infection, children who were younger, children who were undergoing airway surgery, and children whose anesthesia were supervised by less experienced anesthesiologists. Understanding the risk factors and the magnitude of the likely risk should help clinicians make the decision as to whether to anesthetize children with upper respiratory infection.

Intraoperative latex anaphylaxis in children: early detection, treatment, and prevention.

During the past five years, systemic IgE-mediated anaphylactic reactions to latex have been reported more frequently, and a significant proportion of these anaphylactic reactions have occurred intraoperatively. Anaphylactic reactions under general anesthesia occur without warning, and early signs often are obscured by surgical drapes. Therefore, early recognition of symptoms and prevention are essential to avoid catastrophic results. Orthopaedic surgeons must be aware of the risk, diagnosis, prevention, and treatment of latex anaphylaxis. Patients at risk, testing, and prevention are discussed in this review. Additionally, a classification system and the corresponding regimen for prophylaxis that is currently being used at Children's Hospital of Philadelphia is described.

Volumetric capnography in children. Influence of growth on the alveolar plateau slope.

BACKGROUND: Lung growth in children is associated with dramatic increases in the number and surface area of alveolated airways. Modelling studies have shown the slope of the alveolar plateau (phase III) is sensitive to the total cross-sectional area of these airways. Therefore, the influence of age and body size on the phase III slope of the volumetric capnogram was investigated. METHODS: Phase III slope (alveolar dcCO2/dv) and airway deadspace (VDaw) were derived from repeated single-breath carbon dioxide expirograms collected on 44 healthy mechanically ventilated children (aged 5 months-18 yr) undergoing minor surgery. Ventilatory support was standardized (VT = 8.5 and 12.5 ml/kg, f = 8-15 breaths/min, inspiratory time = 1 s, end-tidal partial pressure of carbon dioxide = 30-45 mmHg), and measurements were recorded by computerized integration of output from a heated pneumotachometer and mainstream infrared carbon dioxide analyzer inserted between the endotracheal tube and anesthesia circuit. Experimental data were compared to simulated breath data generated from a numeric pediatric lung model. RESULTS: An increased VDaw, a smaller VDaw/VT, and flatter phase III slope were found at the larger tidal volume (P < 0.01). Strong relationships were seen at VT = 12.5 ml/kg between airway deadspace and age (R2 = 0.77), weight (R2 = 0.93), height (R2 = 0.78), and body surface area (R2 = 0.89). The normalized phase III slopes of infants were markedly steeper than that of adolescents and were reduced at both tidal volumes with increasing age, weight, height, and body surface area. Phase III slopes and VDaw generated from modelled carbon dioxide washout simulations closely matched the experimental data collected in children. CONCLUSIONS: Morphometric increases in the alveolated airway cross-section with lung growth is associated with a decrease of the phase III slope. During adolescence, normalized phase III slopes approximate those of healthy adults. The change in slope with lung growth may reflect a decrease in diffusional resistance for carbon dioxide transport within the alveolated airway resulting in diminished acinar carbon dioxide gradients.

A single dose of morphine sulfate increases the incidence of vomiting after outpatient inguinal surgery in children.

BACKGROUND: In children, opioids are valuable both for their analgesic properties and for their salutary effect on emergence delirium. Although intraoperative administration of opioids is often cited as the cause of postoperative emesis, few data quantitating the magnitude of this effect exist. METHODS: Patients undergoing inguinal surgery as outpatients were randomly assigned to one of two groups. One group received a single intravenous dose of morphine 0.1 mg/kg (morphine group), and the other (control) group had the identical anesthetic but instead received saline. Intravenous ketorolac was administered in response to verbal complaints of pain or a Children's Hospital of Eastern Ontario Pain Score greater than 9 on two successive evaluations performed at 5-min intervals. The authors compared the incidence of postoperative emesis and emergence, behavior, and pain scores between the two groups. RESULTS: Patients in the morphine group (n = 48) were 5.6 +/- 2.8 yr old and weighed 20.8 +/- 7.8 kg, and those in the control group (n = 49) were 4.5 +/- 2.9 yr old and weighed 18.9 +/- 9.2 kg. More patients in the morphine group were cooperative and deeply asleep both on arrival and through the first 30 min of their stay in the postanesthesia care unit (PACU) (P < 0.05). Sixty-three percent of the children in the control group received ketorolac in the PACU compared with 20% of the morphine group (P < 0.01). The incidence of emesis for the 24 h after arrival in the PACU was 56% for those who received morphine compared with 25% in the control group (P < 0.01). CONCLUSIONS: For children undergoing inguinal surgery, the administration of a single dose of intravenous morphine after the induction of anesthesia smooths emergence from anesthesia as assessed by improved cooperation and sedation in the PACU, decreases the need for postoperative analgesics, but increases the incidence of vomiting in the first 24 h after surgery.