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Brian J Anderson

Publications and source records attributed to Brian J Anderson.

31 records · Page 2Linked to original sources
PubMed2004

Intravenous paracetamol (propacetamol) pharmacokinetics in term and preterm neonates.

BACKGROUND: The aim of this study was to describe propacetamol pharmacokinetics in term and preterm neonates to suggest dosing regimens. METHODS. A population pharmacokinetic analysis of paracetamol (acetaminophen) time-concentration profiles in 48 neonates was undertaken using non-linear mixed-effects models. Neonates were given either single (n=30) or multiple doses (n=18) of propacetamol infusion over 15 min. Neonates had a median postnatal age of 1 day (range, 1-76 days). Median post-conceptual age (PCA) was 35 weeks (range, 27-42 weeks), and median weight was 2.4 kg (range, 0.51-4 kg). RESULTS: The population volume of distribution estimate and between-subject variability (%) for a one-compartment model with zero-order input and first-order elimination was 70.4 l (30.7%)/70 kg. Clearance increased from 2.85 l/70 kg, CV 40.7% at 27 weeks PCA to reach 7.05 l/h per 70 kg by 42 weeks PCA (standardised to a 70-kg person using allometric "1/4-power" models). Between-occasion variability for volume of distribution and clearance were 17.4% and 26%, respectively. CONCLUSIONS: A mean paracetamol steady-state target concentration above 10 mg/l at trough can be achieved using a loading dose of 40 mg/kg and maintenance doses of 20 mg/kg 6 h in 28-week PCA neonates, 25 mg/kg 6 h at 32 weeks, 30 mg/kg 6 h at 36 weeks and 20 mg/kg 4 h at term (propacetamol doses). Since the role of the oxidative enzyme CYP2E1 and production of the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine still is unknown in premature neonates, lower doses scaled by age-related clearance and centred on a daily dose of 60 mg/kg per day in a child of 6-8 years with a clearance of 0.25 l/h per kg (12.5 l/h per 70 kg) may be more appropriate.

Acetaminophen↗
PubMed2004

Day stay pediatric tonsillectomy--a safe procedure.

OBJECTIVE: There is a controversy about day stay pediatric tonsillectomy in the UK and Australia. New Zealand has a similar health structure and we wished to compare day stay tonsillectomy from our hospital with those reported from other centers. METHODS: We performed a prospective audit of day stay tonsillectomy to determine conversion to hospital admission rate and the incidence of postoperative hemorrhage. RESULTS: There were 4850 paediatric tonsillectomies performed with 80% of them as day stay procedures over a 9-year study period (1993-2002) in a university-affiliated tertiary children's hospital. The primary postoperative hemorrhage rate (within 24h of surgery) was 0.9% (CI 0.68-1.22%) and 83% occurred within the mandatory 4h postoperative observation period. Primary hemorrhage requiring re-operation to achieve hemostasis occurred in 18 children (0.37%, CI 0.2-0.54%). No child with a primary hemorrhage who presented after discharge following day stay surgery required re-operation or blood transfusion. Day stay surgery was planned in 4041 children and 4.7% (CI 4.1-5.4%) required conversion to hospital admission. Postoperative vomiting was the most common indication for conversion (2.65%, CI 2.2-3.1%), while hemorrhage contributed only 0.95% (CI 0.64-1.24%). CONCLUSIONS: This study was performed in a health system similar to that of Australia and the UK. Complication and conversion rates are similar to those reported in North American centers. Pediatric day stay tonsillectomy is a safe procedure when performed with strict preoperative criteria, trained day stay unit (DSU) staff, and with in-patient facilities on site.

Adolescent↗
PubMed2004

Diclofenac and metabolite pharmacokinetics in children.

BACKGROUND: Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. METHODS: Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. RESULTS: Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. CONCLUSION: The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1) 70 kg(-1)). The rectum is a suitable route for administration of diclofenac in children 2-8 year of age and was associated with a higher relative bioavailabilty than enteric-coated tablets and an earlier maximum concentration (50 vs. 108 min). This pharmacokinetic profile renders diclofenac suppository a suitable formulation for short duration surgery.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Airway management during an EXIT procedure for a fetus with dysgnathia complex.

Nonsyndromal dysgnathia is a rare disorder with a probable genetic basis characterized by a hypoplastic or absent mandible (agnathia), microstomia, microglossia, and ear anomalies secondary to a defect in the ventral portion of the first branchial arch caused by defective neural crest migration or proliferation. Dysgnathic newborn infants often suffer fatal respiratory failure from airway obstruction. Nineteen children with isolated dysgnathia complex are described in the literature--six were stillborn, eight died shortly after birth, and only five survived infancy. All survivors required tracheostomy to maintain an airway. It is difficult to intubate the trachea of these children and early airway management planning is important. We report a neonate who presented with a prenatal ultrasound diagnosis of severe micrognathia, polyhydramnios and a family history of severe micrognathia. Airway management was achieved with fiberoptic intubation through a laryngeal mask airway (LMA) during an ex utero intrapartum treatment procedure. Fiberoptic intubation was hampered by copious amounts of amniotic fluid. This child and her sibling are the first two siblings with isolated dysgnathia complex to have survived infancy and provide further support for a genetic basis to this condition.

Abnormalities, Multiple↗
PubMed2003

Paracetamol and metabolite pharmacokinetics in infants.

BACKGROUND: Data concerning metabolism of paracetamol in infants are scant. Previous studies have examined urinary metabolite recovery rates after a single dose of paracetamol in either neonates (<6 weeks) or children (3-9 years). There are no studies investigating infants. METHODS: Infants ( n=47) undergoing major craniofacial surgery were given paracetamol 19-45 mg/kg 6-, 8-, or 12-hourly as either elixir or suppository formulation for postoperative analgesia, after a loading dose of 33-59 mg/kg rectally during the operation. Serum was assayed for paracetamol concentration in 40 of these infants at 5, 8, 11, 14, 17 and 20 h postoperatively. Urine samples were collected every 3 h for 24 h in 15 of these infants. The clearances of paracetamol to glucuronide and sulphate metabolites as well as the urinary clearance of unmetabolised paracetamol were estimated using non-linear, mixed-effects models. RESULTS: Mean (+/-SD) age and weight of the patients were 11.8+/-2.5 months and 9.1+/-1.9 kg. Clearances of paracetamol to paracetamol-glucuronide (%CV) and to paracetamol-sulphate were 6.6 (11.5) l/h and 7.5 (11.5) l/h respectively, standardised to a 70-kg person using allometric "1/4 power" models. Glucuronide formation clearance, but not sulphate formation, was related to age and increased with age from a predicted value in a neonate of 2.73 l/h/70 kg to a mature value of 6.6 l/h/70 kg with a maturation half-life of 8.09 months. Urine clearance of paracetamol-glucuronide, paracetamol-sulphate and unchanged paracetamol (%CV) were, respectively, 2.65, 3.03 and 0.55 (28) l/h/70 kg. The urine clearance of unchanged paracetamol and metabolites was related to urine volume flow rate. Clearance attributable to pathways other than these measured in urine was not identifiable. The glucuronide/sulphate formation clearance ratio was 0.69 at 12 months of age. Sulphate metabolism contributed 50% towards paracetamol clearance. CONCLUSION: Glucuronide formation clearance increases with age in the infant age range but sulphate formation does not. Renal clearance of paracetamol and its metabolites increases with urine flow rate. This and other studies show that paracetamol metabolism to glucuronide appears to be similar in infants and children, but in adults is increased in comparison with children. Oxidative pathways were undetectable in this infant study and may explain, in part, the reduced incidence of hepatotoxicity in infants.

Acetaminophen↗
PubMed2002

The effects of analgesia in the vulnerable infant during the perinatal period.

Although our knowledge of pain and its management in the perinatal period has increased, little is known about the first hours and days of life when major physiologic transition events occur. Prematurity and critical illnesses further complicate analgesic use during this time. Increased morbidity and mortality have been shown in infants receiving placebo infusions after surgery compared with infants with analgesia, highlighting the negative consequences of pain in infants. Opioids can help promote hemodynamic stability, promote respirator synchrony, and decrease the incidence of grade III & IV intraventricular hemorrhage in ventilated preterm neonates. Long-term follow-up studies suggest improved behavioral and cognitive outcomes in children given morphine infusions during NICU confinement. The necessity of fetal analgesia is dictated by the ability of the fetus to feel pain and by the adverse effects of noxious stimuli on future sensory development. Effects of drugs given to the pregnant woman on the (preterm) newborn might be influenced by decreased or absent transplacental transport, compression of the umbilical cord during delivery, or diminished blood flow in the placenta in pre-eclamptic women, resulting in higher serum concentrations. Pharmacokinetics and drug metabolism change in the last trimester, and pain sensitivity may be altered after 32 weeks of gestation. Consequently, dose and dose interval may vary considerably between neonates and within an individual during the first days of life. This subpopulation is not homogenous, and drug doses in a term neonate with a postnatal age of 2 weeks may be quite different from those at birth and are certainly different from those in a premature neonate. Size must be disentangled from age-related factors when examining developmental pharmacokinetic parameters. There are no longitudinal studies published investigating the pharmacokinetic properties of any analgesic more than once per infant. Polymorphisms of the genes encoding for the enzymes involved in the metabolism of analgesics or in genes involved in receptor expression may contribute to the large interindividual pharmacokinetic parameter variability. Polymorphism of the human mu opioid receptor has not yet satisfactorily explained pharmacodynamic variability.

Analgesia↗
PubMed2002

Jet ventilation for anterior paediatric scoliosis surgery.

Single-lung anaesthesia for thoracotomy is usually achieved with endobronchial intubation, a double-lumen tube or an endobronchial blocker. High-frequency jet ventilation (HFJV) is seldom described for thoracotomy in children, although it is used for both laryngology procedures in the operating room and as a ventilation mode in intensive care. HFJV was used in three children, aged 10-12 years, who presented for scoliosis correction involving thoracotomy. The jet ventilation catheter was passed through a tracheal tube to reduce the risk of outflow obstruction and allow a smooth conversion to intermittent positive-pressure ventilation when required. Mean airway pressures measured at the tip of the HFJV catheter were at or below 4 cmH2O. Surgical opening of the nondependent lung pleura resulted in sufficient collapse of the pulmonary parenchyma with the patient in the lateral decubitus position for the surgical procedure. Arterial blood gas analyses performed during thoracotomy were within normal limits, with no CO2 retention. HFJV is an alternative ventilation strategy for thoracotomy in children because of its unique ability to deliver small tidal volumes at low mean airway pressures via a narrow catheter.

Blood Gas Analysis↗
PubMed2002

Use of ultrasound bladder monitoring in children after caudal anaesthesia.

Urinary retention occurring after caudal anaesthesia in children has a low incidence. Most children will void within 12 h of surgery, although the incidence of retention is higher after hypospadias repair. However, overdistention causing bladder atony that is temporary, or may become permanent, is described in adults. Long-term effects of overdistention in children have not been described. Urine volume, used to describe overdistention, is traditionally measured after catheterization. We report two children suffering from urine retention after caudal anaesthesia (bupivacaine 0.25%) was used to supplement a general anaesthetic. Ultrasound bladder monitoring was used to assist with the clinical diagnosis of bladder distension in the postanaesthesia care unit (PACU) and subsequent management. In-out catheterization was required in a 1-year-old-girl with a bladder volume of 12 ml.kg-1 after external manual compression over the bladder was unable express urine. Spontaneous micturation occurred within the subsequent 8 h. A 10-year-old boy suffered distress in PACU with a bladder volume, measured by ultrasound, of 5 ml.kg-1. Catheterization relieved distress and spontaneous micturation returned 18 h after surgery. Measured urine volumes were similar to those estimated by ultrasound. Ultrasound bladder monitoring is a simple, noninvasive technique that can be used to assist with the diagnosis and management of urinary retention in children. It may replace catheterization as the prefered technique to measure urine volume. The correlation between measured bladder volumes and urine volume appears reasonable. A volume of approximately 10 mg.kg-1 may be considered as causing overdistension.

Anesthesia, Caudal↗
PubMed2002

Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis.

BACKGROUND: The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens. METHODS: A population pharmacokinetic analysis of acetaminophen time-concentration profiles in 283 children (124 aged < or = 6 months) reported in six studies was undertaken using nonlinear mixed-effects models. Neonates and infants were given either single or multiple doses of four different formulations: oral elixir, rectal solution, or triglyceride or capsular suppository. The median postnatal age of children younger than 6 months was 1 day (range, birth to 6 months), median postconception age was 40 weeks (range, 28-64 weeks), and median weight was 3.1 kg (range, 1.2-9.0 kg). RESULTS: Population pharmacokinetic parameter estimates and their variability (percent) for a one-compartment model with first-order input, lag time, and first-order elimination were as follows: volume of distribution, 66.6 l (20%); clearance, 12.5 l/h (44%); standardized to a 70-kg person using allometric "1/4 power" models. The volume of distribution decreased exponentially with a maturation half-life of 11.5 weeks from 109.7 l/70 kg at 28 weeks after conception to 72.9 l/70 kg by 60 weeks. Clearance increased from 28 weeks after conception (0.74 l x h(-1) x 70 kg(-1)) with a maturation half-life of 11.3 weeks to reach 10.8 l x h(-1) x 70 kg(-1) by 60 weeks. The absorption half-life for the oral elixir preparation was 0.21 h (120%) with a lag time of 0.42 h (70%), but absorption was further delayed (2 h) in premature neonates in the first few days of life. Absorption half-life parameters for the triglyceride base and capsule suppositories were 0.80 h (100%) and 1.4 h (57%), respectively. The absorption half-life for the rectal solution was 0.33 h. Absorption lag time was negligible by the rectal route for all three formulations. The bioavailability of the capsule suppository relative to elixir decreased with age from 0.92 (22%) at 28 weeks after conception to 0.86 at 2 yr of age, whereas the triglyceride base decreased from 0.86 (35%) at 28 weeks postconception to 0.5 at 2 yr of age. The relative bioavailability of the rectal solution was 0.66. CONCLUSIONS: A mean steady state target concentration greater than 10 mg/l at trough can be achieved by an oral dose of 25 mg x kg(-1) x d(-1) in premature neonates at 30 weeks' postconception, 45 mg x kg(-1) x d(-1) at 34 weeks' gestation, 60 mg x kg(-1) x d(-1) at term, and 90 mg x kg(-1) x d(-1) at 6 months of age. The relative rectal bioavailability is formulation dependent and decreases with age. Similar concentrations can be achieved with maintenance rectal doses of 25 (capsule suppository) or 30 (triglyceride suppository) mg. kg-1. d-1 in premature neonates at 30 weeks' gestation, increasing to 90 (capsule suppository) or 120 (triglyceride suppository) mg x kg(-1) x d(-1) at 6 months. These regimens may cause hepatotoxicity in some individuals if used for longer than 2-3 days.

Absorption↗