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.

Infant botulism: a review of 12 years' experience at the Children's Hospital of Philadelphia.

Fifty-seven patients with infant botulism were cared for at The Children's Hospital of Philadelphia between 1976 and 1987. The ages of the children ranged from 18 days to slightly more than 7 months. The average duration of hospitalization was 44 +/- 34 days, with the average intensive care unit stay lasting 29 +/- 25 days (54 of 57 patients). The majority (77%) of the patients were ultimately intubated and mechanically ventilated (68%). The principal indication for intubation was loss of protective airway reflexes and not hypercarbia or hypoxemia. In those patients who required mechanical ventilation the average duration was 23 +/- 22 days, with the 10 most severely affected patients (greater than or equal to 28 days of mechanical ventilation) averaging 53 +/- 25 days. Excluding patients ventilated for more than a month, those who underwent tracheostomy were hospitalized nearly twice as long as those who were managed by nasotracheal intubation only (33.5 days vs 63.2 days). The use of continuous nasogastric feedings has supplied most infants with sufficient enteral feedings to avoid weight loss and the need for central intravenous alimentation.

Management of Reye's syndrome.

Reye's syndrome is a potentially devastating neurologic illness seen predominantly in children following a viral prodrome. The cause is unknown. The clinical history and laboratory presentation are stereotypical and easy to recognize if the clinician considers the diagnosis. Neurologic dysfunction is characterized by lethargy, obtundation, persistent vomiting, agitated delirium, and coma. Death is secondary to severe cerebral swelling with elevation of intracranial pressure. Although no specific therapy has been clearly demonstrated to be superior in terms of outcome, most clinicians have adopted a management scheme aimed at lowering and controlling the elevated ICP. We have described the management protocol in use at the Children's Hospital of Philadelphia. The protocol is summarized in the Appendix for the convenience of the reader.

Preoperative and postoperative fasting in children.

This article addresses the preoperative fast in the context of its historic background, the physiology of gastric emptying, and recent clinical studies. A rationale is developed for minimizing the traditional preoperative fasting interval for elective surgery. The timing and the necessity for patients to resume ingesting clear liquids in the postoperative period is also explored.

Pediatric home mechanical ventilation.

Infants and children with chronic respiratory failure are a byproduct of improvements in intensive care medicine. Home mechanical ventilation is an alternative to hospital care for the ventilator-assisted child. With proper preparation, safeguards, and support, these children are being successfully managed at home.

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 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.

Shortened preanesthetic fasting interval in pediatric cardiac surgical patients.

The recent liberalization of preoperative feeding orders in healthy pediatric outpatients prompts the question of whether this applies to children about to have cardiac surgery. The authors compared gastric fluid volume and pH in two groups of children undergoing elective cardiac surgery, one of which was not only permitted ad libitum clear liquids but was mandated to drink clear liquids 2-3 h before induction of anesthesia (study group). The other group followed routine inpatient preoperative fasting orders (control group). The study group (n = 44) averaged 3.1 +/- 4.1 yr and weighed 15.3 +/- 16.3 kg; the control group averaged 3.3 +/- 3.9 yr and weighed 14.3 +/- 12.1 kg (P = 0.82, 0.73, respectively). Aspiration of residual gastric fluid volume was attempted in all patients after induction of anesthesia. Gastric fluid volume averaged 0.6 +/- 0.9 mL/kg in the study group and 0.4 +/- 0.6 mL/kg in the control group (P = 0.13). Of the study patients, 41% had a measured gastric volume greater than or equal to 0.4 mL/kg compared with 32% of the control patients (P = 0.50). Of the 42 patients who had residual gastric fluid aspirated, pH determinations were completed on 37 aspirates; of these 19 of 20 (95%) in the study group and 14 of 17 (82%) in the control group had a gastric pH less than or equal to 2.5. Using a linear analogue scale, parents rated children in the study group to be more comfortable, less hungry, and less thirsty compared with the control patients (P = 0.004, 0.002, 0.0001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of heavy water for indicator dilution cardiac output measurement.

We evaluated deuterium oxide (D2O) as a tracer for cardiac output measurements. Cardiac output measurements made by thermodilution were compared with those made by indicator dilution with D2O and indocyanine green as tracers. Five triplicate measurements for each method were made at intervals of 30 minutes in each of 9 anesthetized, mechanically ventilated goats. Cardiac output ranged between 0.68 and 3.79 L/min. The 45 data points yielded a correlation coefficient of 0.948 for the comparison of D2O indicator dilution cardiac output measurements with thermodilution measurements and a linear regression slope of 1.046. D2O indicator dilution measurements were biased by -0.11 +/- 0.22 L/min compared with thermodilution measurements and had a standard deviation of +/- 0.12 L/min for triplicate measurements. Hematocrits ranging between 20 and 50 vol% had no effect on optical density for D2O. D2O is more stable than indocyanine green and approximately one-tenth the price (40 cents per injection compared with $4). The basic instrumentation cost of approximately $9,000 is an additional initial expense, but provides the ability to perform pulmonary extravascular water measurements with a double-indicator dilution technique. D2O has potential as a tracer for the clinical determination of indicator dilution cardiac output measurements and pulmonary extravascular water measurements.

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.

Ingestion of liquids compared with preoperative fasting in pediatric outpatients.

The preoperative fast is often an unpleasant preoperative experience that might be alleviated by allowing children to drink clear liquids. The authors compared gastric fluid volume and pH in two groups of children, one of whom was permitted clear liquids until 2 h before surgery (study group) and the other followed routine preoperative fasting orders (control group). The study group was not limited in the quantity of clear liquid allowed with the exception that the last intake prior to surgery was limited to 8 ounces. The study group (n = 53) averaged 5.9 +/- 5 yr and weighed 23.6 +/- 17 kg, while the control group averaged 7.3 +/- 4.6 yr and weighed 29 +/- 17.7 kg (P = NS). Gastric contents were aspirated following induction of anesthesia. Gastric fluid volume averaged 0.44 +/- 0.51 ml/kg for study group and 0.57 +/- 0.51 ml/kg in the control group (P = 0.12). Of the study patients, 48% had a measured gastric fluid volume greater than or equal to 0.4 ml/kg compared with 58% of the control patients (P = 0.77). Eighty three patients had sufficient gastric fluid for pH determination; of these 34/35 (97%) in the study group and 44/48 (92%) in the control group had a gastric fluid pH less than or equal to 2.5. Using a linear analog scale parents rated the children in the study group to be less irritable (P less than 0.001) and to have had a better overall preoperative experience (P less than 0.01) compared with the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic respiratory failure in infants with prolonged ventilator dependency.

One hundred one infants with chronic respiratory failure (CRF) who required prolonged mechanical ventilation were cared for in the pediatric intensive care unit at The Children's Hospital of Philadelphia between January 1967 and December 1984. Chronic respiratory failure of infancy is a condition that requires mechanical ventilation for more than 28 days in the first year of life. Thirty-six children had severe bronchopulmonary dysplasia, 50 had congenital anomalies, and 15 had neuromuscular disorders. The mean duration of mechanical ventilation for the 101 patients was 12.3 months. Seventy-one children were alive, and 53 (75%) of the 71 had been weaned from mechanical ventilation as of Dec 31, 1984. Pulmonary insufficiency and cardiac failure were the predominant causes of death in 17 of 22 infants in the first two years after the onset of CRF; four of eight deaths that occurred beyond two years were caused by airway- and ventilator-related accidents. Mechanical ventilatory support was emphasized for as long as necessary to provide normal blood gas tensions, nutrition, growth, and development rather than weaning as rapidly as possible. This clinical experience demonstrates that it is feasible to save over 70% of infants with the severest forms of CRF and prolonged ventilator dependency.

Should children drink before discharge from day surgery?

The ability to drink clear liquids without vomiting after anesthesia and surgery is a commonly used criteria for discharge of pediatric day surgery patients. We hypothesized that the ability to drink as a prerequisite for discharge would not affect the frequency of vomiting, delay discharge, or increase the frequency of readmission of children for dehydration after day surgical procedures. We randomized 989 patients between the ages of 1 month and 18.0 yr to one of two groups. The 464 "mandatory drinkers" were required to demonstrate the ability to drink clear liquids without vomiting prior to discharge from the hospital, whereas 525 "elective drinkers" were allowed but not required to drink. Other than the discharge criteria, the patients were managed in an identical fashion; the minimum volume of intravenous fluids received by all patients was adequate to supply a calculated 8-h fluid deficit prior to discharge from the hospital. There were no differences between the two groups in the incidence of vomiting in the operating room, the postanesthesia care unit, or after discharge from the hospital. However, in the day surgery unit, only 14% of the elective drinkers vomited compared to 23% of the mandatory drinker group (P less than 0.001). The mandatory drinkers had a more prolonged stay in the day surgical unit, averaging 101 +/- 58 min (mean +/- SD) compared to 84 +/- 40 min for elective drinkers (P less than 0.001). No patient in either group required admission to the hospital for persistent vomiting on the day of surgery, and no patient required readmission for vomiting or dehydration after discharge from the day surgery unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of alfentanil on intracranial pressure in children undergoing ventriculoperitoneal shunt revision.

The effects of alfentanil on intracranial pressure in patients with diminished intracranial compliance has not been established. Ten patients with hydrocephalus of varying etiologies, ages 16 months to 20 yr, presenting for ventriculoperitoneal shunt revision were studied. Following induction of anesthesia with thiopental, nitrous oxide/oxygen, and isoflurane, the trachea was intubated and anesthesia was maintained with isoflurane (0.5%), nitrous oxide (70%), and oxygen. After a minimum of 30 min and after the new shunt was placed, alfentanil was administered in increments of 10, 20, and 40 micrograms/kg at 3-min intervals, and intracranial pressure was measured over 12 min via the new shunt. In these unstimulated, normocapnic (PETCO2 32-38 mmHg) patients, heart rate, mean arterial pressure, and cerebral perfusion pressure declined from 110 +/- 26 beats/min, 90 +/- 11 mmHg, and 71 +/- 14 mmHg, to 84 +/- 25 beats/min, 66 +/- 11 mmHg, and 45 +/- 16 mmHg (mean +/- SD), respectively, by 3 min after the third dose (P less than 0.001). Intracranial pressure did not change from baseline (19 +/- 14 mmHg vs. 21 +/- 11) after any dose of alfentanil. Contrary to earlier studies in adult patients with brain tumors, the authors found that alfentanil, in pediatric patients with hydrocephalus anesthetized with oxygen, nitrous oxide, and isoflurane, did not increase intracranial pressure within a 9-min study period. The significant decreases in cerebral perfusion pressure observed merit concern and further study.

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.

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.

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: 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.

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.