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N S Morton

Publications and source records attributed to N S Morton.

At least 19 recordsLinked to original sources
PubMed2005

High-performance liquid chromatography determination of alpha1-acid glycoprotein in small volumes of plasma from neonates.

In order to investigate how the alpha1-acid glycoprotein (AGP) concentrations of neonates change in response to surgical stress, a simple high-performance liquid chromatography (HPLC)-assay for the measurement of alpha1-acid glycoprotein levels was developed. A fraction containing alpha1-acid glycoprotein was isolated from the bulk of plasma protein by addition of 0.6M perchloric acid and was then analysed directly on a short PLRP-S 4000A reversed phase column column. The method was validated by analysis of pooled plasma from healthy adults both in comparison with a calibration curve and by standard additions. The procedure was able to isolate alpha1-acid glycoprotein rapidly (<30 min) and required only 50 microl of plasma. The mean extraction recovery was 79.1% (CV 6.4%). The within-run precision for the analysis of three replicates of quality control sample ranged from +/-1.2 to +/-3.8% and the between-run precision was +/-6.1%. The method was linear (r(2)=0.988) over a concentration range from 6 to 100.0 mg/100 ml. The AGP levels in neonatal samples ranged from 25 to 93 mg/100 ml.

Adult↗
PubMed2002

A simple microanalytical technique for the determination of paracetamol and its main metabolites in blood spots.

The use of blood spot collection cards is a simple way to obtain specimens for analysis of drugs with a narrow therapeutic window. We describe the development and validation of a microanalytical technique for the determination of paracetamol and its glucuronide and sulphate metabolites from blood spots. The method is based on reversed phase high-performance liquid chromatography with ultraviolet detection. The limit of detection of the method is 600 pg on column for paracetamol. Intra- and inter-day precision of the determination of paracetamol was 7.1 and 3.2% respectively. The small volume of blood required (20 microl), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring paracetamol concentrations. The method was applied to the analysis of blood spots taken from neonates being treated with paracetamol.

Acetaminophen↗
PubMed2001

Treatment with paracetamol in infants.

BACKGROUND: Paracetamol (N-acetyl-p-amino-phenol) or acetaminophen has become the most widely used analgesic and antipyretic in children. However, there is a wide discrepancy between the extent to which paracetamol is used and the limited available pharmacological data in small infants. The purpose of this article is to present a review of the current literature regarding the use of paracetamol in neonates and infants with a particular emphasis on pharmacological issues. METHODS: A MEDLINE search (up to March 2000) was conducted to identify relevant English-language publications using paracetamol, children, infants and neonates as search terms. Additional studies were identified from bibliographies of the reviewed literature. RESULTS: Pharmacological studies on paracetamol in infants are few. Most studies have focused on the administration of one single paracetamol dose, and the problem of cumulative toxicity with repeated dosing has not been addressed. Plasma paracetamol concentration should be 10-20 mg ml(-1) to achieve antipyretic and analgesic effects. The bioavailability of the different formulations and routes of administration vary with age. Rectal absorption is slower and more erratic than the oral; however, in the very young, rectal bioavailability is higher than in older patients. Volume of distribution seems to be age-independent, whereas clearance is reduced in neonates and particularly in preterm babies. Neonates and infants are capable of forming the reactive intermediate metabolite that causes hepatocellular damage, particularly after multiple doses. They have an immature glucuronide conjugation system, but the rate constant for the sulphation metabolic pathway is larger than in older children, and this is the most important route of metabolism. CONCLUSIONS: The pharmacokinetics and pharmacodynamics of paracetamol differ substantially in neonates and infants from those in older children and adults; hence, dosing should be adjusted accordingly.

Acetaminophen↗
PubMed2001

Plasma concentrations and pharmacokinetics of bupivacaine with and without adrenaline following caudal anaesthesia in infants.

BACKGROUND: The aim of this study was to determine whether the use of adrenaline 1/400000 added to 0.25% bupivacaine significantly delays the systemic absorption of the drug from the caudal epidural space in young infants. METHODS: Fifteen infants less than 5 months of age undergoing minor lower abdominal procedures under a standardised general anaesthetic were randomised to receive a caudal block with either 0.25% plain bupivacaine 2.5 mg/kg (n=7) or bupivacaine 0.25% with 1/400000 adrenaline (n=8). Blood samples were drawn at 30, 60, 90, 180, 240 and 360 min according to the infant's weight and analysed for total and free bupivacaine concentrations using a gas chromatography-mass spectrometry (GC-MS) technique. RESULTS: The total C(MAX) and T(MAX) were comparable in both groups. The total bupivacaine concentration at t=360 min was significantly higher in the "adrenaline" group compared to the "plain" group, i.e. a median (range) 742 ng/ml (372-1423 ng/ml) vs. 400.5 ng/ml (114-446 ng/ml), P=0.0080. The median "apparent" terminal half-life (t1/2) was significantly longer in the "adrenaline" group (363 min; range 238-537 min) compared to the "plain" group (n=6) (165 min; range 104-264 min), P=0.0087. The free bupivacaine concentrations (n=3 in both groups) ranged between 13 ng/ml and 52 ng/ml, corresponding to a percentage of free bupivacaine between 1.3% and 6.7%. CONCLUSION: The addition of 1/400.000 adrenaline prolongs the systemic absorption of caudally administered bupivacaine in infants less than 5 months of age.

Algorithms↗
PubMed2001

Review of ethics in paediatric anaesthesia: consent issues.

The concepts of law and ethics as related to medical practice have always been of paramount importance to the medical profession. This series of three reviews, examines the changes in the law in the last 10 years in relation to ethics and the practice of paediatric anaesthesia. The reviews cover, in a practical question and answer format, the topics of consent, research, intensive care and organ donation issues in children.

Anesthesia↗
PubMed2001

Review of ethics in paediatric anaesthesia: research issues.

This is the second of a series of three articles reviewing the recent changes in the law in relation to ethics and the practice of paediatric anaesthesia. The review covers, in a practical question and answer format, the topics of consent, research, intensive care issues and organ donation in children.

Anesthesia↗
PubMed2001

Review of ethics in paediatric anaesthesia: intensive care issues.

This is the third of a series of three articles examining the recent changes in the law in relation to ethics and the practice of paediatric anaesthesia. The review covers, in a practical question and answer format, the topics of consent, research, intensive care issues and organ donation in children.

Anesthesiology↗
PubMed2000

Determination of free concentrations of ropivacaine and bupivacaine in plasma from neonates using small-scale equilibrium-dialysis followed by liquid chromatography-mass spectrometry.

Attempts to determine a safe plasma concentration of ropivacaine and bupivacaine in neonates have not been consistent. This might be due to an underestimation of free drug in small plasma samples by currently used techniques, e.g., ultrafiltration. We describe a simple microscale equilibrium-dialysis technique for the separation of free and bound ropivacaine and bupivacaine. The free drug in the dialysate was determined using solid-phase extraction and liquid chromatography with mass spectrometry. Pentycaine was used as an internal standard and added to the dialysates prior to extraction. The method is very selective and sensitive, as no compounds other than the analyte and internal standard were observed in the resulting chromatograms at low ng/ml levels. The limit of quantitation was 2.5 ng/ml. The calibration curve was linear in the range of 2 to 1000 ng/ml. The precision of the whole procedure was 8.1% (n=10) and 6.5% (n=7) for ropivacaine and bupivacaine, respectively. The method was tested in the analysis of plasma samples taken from neonates who had received epidural injections.

Amides↗
PubMed1999

Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants.

BACKGROUND: Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants. METHODS: Perioperatively, 17 neonates and infants < or =160 days of age received one rectal paracetamol dose (mean 23.9 mg/kg (+/-4.2 mg/kg)). Blood samples were drawn at 60, 120, 180, 240, 300 and 360 min, according to the infants' weights. Plasma paracetamol concentrations were measured by a Colorometric Assay, Ectachem Clinical Chemistry Slides (Johnson & Johnson Clinical Diagsnostics). RESULTS: The plasma paracetamol concentrations were mainly below the therapeutic (i.e. antipyretic) range of 66-132 micromol/l and did not exceed 160 micromol/l in any infant. The mean maximum plasma concentration (Cmax) was 72.4 micromol/l (+/-33.5 micromol/l) and the time to Cmax, i.e. the mean Tmax was 102.4 min (_+59.1 min). The mean "apparent" terminal half-life (n=10) was 243.6 min (+/-114.1 min). CONCLUSION: The absorption of rectal paracetamol (mean dose 23.9 mg/kg, +/-4.2mg/kg) in young infants <160 days is variable and often prolonged and achieves mainly subtherapeutic plasma concentrations.

Absorption↗
PubMed1999

Paracetamol-induced fulminant hepatic failure in a child after 5 days of therapeutic doses.

We report the case of a two and a half year-old girl who developed fulminant hepatic failure following 5 days of regular oral ingestion of paracetamol, approximately 90 mg x kg-1 x day-1. She presented with the typical findings of hepatomegaly, encephalopathy, high ammonia levels, high transaminases, hypoglycaemia and lactic acidosis. After stabilization, she was transferred to a specialist paediatric liver failure unit and fortunately she made a full recovery with intensive medical management.

Acetaminophen↗
PubMed1999

Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine.

We studied 80 children, aged 5-13 yr, who received PCA with morphine after appendicectomy using a standardized tracheal general anaesthetic. All patients received morphine 0.1 mg kg-1 before surgical incision and all had wound infiltration with bupivacaine 1 mg kg-1 at the end of surgery. Patients were allocated randomly to receive postoperative analgesia with PCA morphine alone, morphine plus diclofenac 1 mg kg-1, morphine plus paracetamol 15-20 mg kg-1 or morphine plus a combination of both diclofenac and paracetamol. Cumulative morphine consumption was significantly reduced by concurrent administration of diclofenac but no additive effect of paracetamol was demonstrable with the doses used in the study. Analgesia, as assessed by movement pain scoring, was significantly improved by the addition of diclofenac despite lower morphine consumption. Adverse effects and duration of PCA were comparable in the four groups.

Acetaminophen↗
PubMed1998

Tracheal intubation without neuromuscular blockade in children: a comparison of propofol combined either with alfentanil or remifentanil.

Forty healthy children, aged between two and 12 years of age undergoing elective surgery where the anaesthetic technique involved tracheal intubation followed by spontaneous ventilation were studied. Induction of anaesthesia was with either alfentanil 15 micrograms.kg-1 or remifentanil 1 microgram.kg-1 followed by propofol 4 mg.kg-1 to which lignocaine 0.2 mg.kg-1 had been added. Intubating conditions were graded on a four point scale for ease of laryngoscopy, vocal cord position, degree of coughing, jaw relaxation and limb movement. All children were successfully intubated at the first attempt. There were no significant differences in the assessments of intubating conditions between the two groups. Arterial blood pressure and heart changes were similar in the two groups with both alfentanil and remifentanil attenuating the haemodynamic response to tracheal intubation. The time taken to resumption of spontaneous ventilation was similar in both groups.

Alfentanil↗
PubMed1998

Development of a selection and monitoring protocol for safe sedation of children.

A protocol was developed for children undergoing diagnostic and therapeutic procedures under sedation to try to raise the standards of patient selection, preparation, monitoring and management to those of children undergoing general anaesthesia. The principles underlying the protocol design were that informed consent should be obtained; fasting guidelines as for general anaesthesia should be implemented; contraindications to sedation should be actively sought; monitoring should be commenced from the time of administration of sedation until recovery and should be maintained during patient transport; personnel trained in monitoring and resuscitation of children should have as their sole duty the monitoring of the sedated child and should not take part in the procedure; the minimum monitoring standard should comprise regular assessments of the level of sedation, oxygen saturation by pulse oximetry, respiratory rate and pulse rate supplemented by temperature, ECG and blood pressure for infants, for prolonged procedures or where verbal contact with the child is lost.

Child↗