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Biomedical subjects

T G Hansen

Publications and source records attributed to T G Hansen.

At least 19 recordsLinked to original sources
PubMed2004

Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair: a double-blind study.

BACKGROUND: Clonidine is used increasingly in paediatric anaesthetic practice to prolong the duration of action of caudal block with a local anaesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and i.v. clonidine on postoperative analgesia produced by caudal bupivacaine after hypospadias repair. METHODS: Forty-six children (ASA I or II) aged 24-104 months received standardized premedication with midazolam, a general anaesthetic and a caudal block with bupivacaine 0.25%, 0.5 ml kg(-1). The children were randomized in a double-blind fashion to two groups: the i.v. group received clonidine 2 micro g kg(-1) i.v. and simultaneously the same volume of saline caudally. The caudal group received clonidine 2 micro g kg(-1) caudally and a similar volume of saline i.v. After surgery, all children received acetaminophen 20 mg kg(-1) rectally or orally 6-hourly and were given a patient-controlled or nurse-controlled analgesia (PCA/NCA) pump with i.v. morphine (bolus of 25 micro g kg(-1) and an 8-min lockout period with no background infusion). Monitoring of scores for pain, sedation, motor block, and postoperative nausea and vomiting was performed by nurses blinded to the study allocations. Time to first activation of the PCA/NCA pump and 0-24 h and 24-48 h morphine consumption were also recorded. RESULTS: Forty-four children completed the study. Age, weight and duration of anaesthesia and surgery were similar in the two groups. The median (range) time to first activation of the PCA/NCA pump was similar in the two groups: 425 (150-1440) min in the i.v. group and 450 (130-1440) min in the caudal group. The number of children not requiring postoperative morphine was four and seven respectively. Morphine consumption during 0-24 h and 24-48 h was similar between groups. CONCLUSIONS: The analgesic effect of clonidine 2 micro g kg(-1) as an adjunct to caudal block with bupivacaine 0.25%, 0.5 ml kg(-1) is similar whether administered i.v. or caudally.

Adrenergic alpha-Agonists↗
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

Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations.

BACKGROUND: Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months. METHODS: Two groups of infants (group 1 [n = 15], aged 0-3 months; group 2 [n = 15], aged 3-12 months) were given a caudal bolus dose of 0.2% ropivacaine (2 mg/kg) and a standardized general anesthetic technique. Serial blood samples taken for up to 12 h were analyzed for total and free ropivacaine using high-performance liquid chromatography. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the kinetic parameters also was made. RESULTS: Median maximum free ropivacaine concentration was significantly higher in group 1 (99 micog/l) than in group 2 (38 microg/l) (P = 0.0002), as was the median free fraction of ropivacaine (10% vs. 5%; P = 0.01). Pharmacokinetic variables of the total population were best described by a one-compartment model with first-order absorption. Mean clearance was 0.31 l.h(-1).kg(-1) (coefficient of variation [CV], 51%), volume of distribution was 2.12 l/kg (CV, 34%), and absorption rate constant was 1.61 h(-1) (CV, 46%). Mean absorption and elimination half-lives were 0.43 and 5.1 h, respectively. Age and percentage of free ropivacaine were significant covariates for clearance. Posterior Bayesian estimates of clearance were significantly higher (38%) in older children. CONCLUSION: Total and free plasma ropivacaine concentrations after caudal ropivacaine (0.2%, 2 mg/kg) in infants were within the range of concentrations previously reported in adults and older children. Age and percentage of free ropivacaine were significant covariates of clearance.

Age Factors↗
PubMed2000

Pharmacokinetics and clinical efficacy of long-term epidural ropivacaine infusion in children.

The clinical efficacy and pharmacokinetics of long-term epidural ropivacaine infusion were investigated in 18 postoperative children aged between 0.3 and 7.3 yr. A lumbar or thoracic epidural catheter was inserted after the anaesthetic induction. Sixty minutes following a bolus dose of ropivacaine 1 mg kg-1, 0.2% ropivacaine was infused at a fixed rate of 0.4 mg kg-1 h-1 for a mean of 61.3 h (range 36-96 h). Clinical evaluation comprised hourly recording of pain, sedation, motor block, nausea/vomiting, pruritus-scores, SpO2, pulse and respiratory rates, and recording of non-invasive arterial pressure every 4 h. Total and free plasma concentrations were measured by high-performance liquid chromatography at 0, 1, 6, 12, 24, 36, 48, 72 and 96 h. Analgesia was of high quality and side effects were minor. No clinical signs of local anaesthetic toxicity were seen. Total (100-3189 micrograms litre-1) and free (10-56 micrograms litre-1) ropivacaine concentrations were within the range reported to be 'safe' in previous studies in adults. Mean (95% CI) volume of distribution was 3.1 litre kg-1 (2.1-4.2 litre kg-1), total clearance was 8.5 ml kg-1 min-1 (5.8-11.1 ml kg-1 min-1), free clearance was 220 ml kg-1 min-1 (170-270 ml kg-1 min-1) and elimination half-life was 4.9 h (3.0-6.7 h).

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↗
PubMed1998

The peri-operative cytokine response in infants and young children following major surgery.

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10 and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early increase in the interleukin-1 receptor antagonist levels at the end of surgery was seen. The other cytokines were only detectable at low concentrations among a minority of children. In conclusion, this study showed highly variable peri-operative cytokine responses in infants and young children undergoing major surgery.

Anesthesia, Epidural↗
PubMed1998

Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery.

Cardiac and major abdominal surgery are associated with granulocytosis in peripheral blood. The purpose of the present study was to describe the granulocyte and monocyte oxidative burst and the expression of adhesion molecules following cardiac surgery with cardiopulmonary bypass and abdominal surgery. The ability to respond with an oxidative burst was measured by means of flow cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18, CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from eight patients undergoing open-heart surgery were taken before surgery, 1, 5, 10 and 20 min after aortic clamping, and then 1, 5, 10 and 20 min and 1, 2 and 3 h after declamping. Samples from eight patients undergoing abdominal surgery were taken before surgery, at the end of surgery, and 2 and 3 h post-operatively. A decrease in number of granulocytes and monocytes during cardiopulmonary bypass was observed. The percentage of CD11a-positive granulocytes increased from 30% pre-operatively to 75% following cardiopulmonary bypass, while CD44-positive granulocytes increased from 5% to 13%. Despite the extent of the changes, these were not significant. The oxidative burst of the granulocytes and monocytes decreased after declamping to 15% and 27% of initial values in vitro. Several hours after surgery, there was no significant difference between the two groups. These results can be explained by a granulocyte and monocyte refractory response developing subsequent to an increased per-operative oxidative burst activity, and the induction of adhesion molecules on granulocytes associated with the cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with cardiopulmonary bypass was associated with a rapid and pronounced activation of leukocytes which may play a role in reperfusion injury.

Antibodies, Monoclonal↗
PubMed1998

Haemolysis following rapid experimental red blood cell transfusion--an evaluation of two infusion pumps.

BACKGROUND: The vast majority of infusion pumps used for rapid transfusion of large amounts of blood have never been properly examined regarding their influence on the quality of the red blood cells (RBCs) infused. In this study, we evaluated the effect of two different infusion pumps on the degree of RBC destruction following rapid experimental blood transfusion. METHODS: Divided into 2 groups according to age, 30 u of SAGM RBCs were infused through an experimental transfusion model by either a manual roller pump (MRP) or a pressure infusor pump (PIP). Fresh (i.e stored for 8-11 d) RBCs, 20 u, and 10 u of older (i.e. stored for 25-33 d) RBCs were randomly allocated to infusion with either of the two pumps. The rate of infusion was as fast as possible with the MRP, and with the PIP adjusted with an external applied pressure of 300 mm Hg. RBC samples collected before and after infusion were analyzed for total haemoglobin, free haemoglobin, haematocrit, total free potassium, lactate dehydrogenase (LDH) and the percentage of haemolysis. The time spent for each transfusion was measured by a stop watch. RESULTS: Following infusion, a marginal increase (i.e. considerably below 0.8%) in the percentage of haemolysis and LDH content was seen with both pumps. This increase was only statistically significant when RBCs stored for 8-11 d were used (P = 0.002 for both parameters). Irrespective of the age of the RBCs, no differences between the two pumps could be detected. Compared to the PIP, infusion with the MRP could be accomplished significantly faster, i.e. median 5.9 ml/s (5.2-6.4 ml/s) versus 2.9 ml/s (2.5-3.2 ml/s), (P < 0.0001). CONCLUSIONS: Both the pumps used in this study are safe alternatives for rapid transfusion of RBCs; however, with MRP this can be accomplished approximately twice as fast as with the PIP.

Adenine↗