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Biomedical subjects

D Ostergaard

Publications and source records attributed to D Ostergaard.

At least 19 recordsLinked to original sources
PubMed2001

Management of anaphylactic shock evaluated using a full-scale anaesthesia simulator.

BACKGROUND: The diagnosis of an anaphylactic reaction during anaesthesia is not the first consideration for the anaesthetist and might be missed. The aim of this study was to describe anaesthetists' management of an anaphylactic reaction concerning diagnosing, treatment and application of anaesthesia crisis resource management (ACRM) in a full-scale anaesthesia simulator. METHODS: Forty-two anaesthetists in teams of two attended training sessions with a critical incident of anaphylactic shock in a full-scale simulator. Trained observers from the study group evaluated the medical treatment according to a treatment sequence developed from the literature and graded the ACRM performance on a five-point scale where 1 is bad and 5 is best. RESULTS: None of the teams made the correct diagnosis within 10 min and treatment according to the treatment sequence was not initiated. Only 6/21 teams considered the right diagnosis but first after hints from the instructor 15 min after the start of the incident. Evaluation of the use of the total ACRM concept (that is the use of all of the ACRM expressions seen in a total connection: called general impression) gave a median value of 2.0 with a range of (1-3). CONCLUSION: Anaphylactic shock was difficult to diagnose and no structured plans were used for the treatment in the simulated incident in this study.

Anaphylaxis↗
PubMed2001

Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery.

BACKGROUND: Our aim was to study the pharmacokinetics and pain scores following administration of single oral doses of either diclofenac or high-dose acetaminophen (paracetamol). METHODS: In the morning, the day after tonsillectomy, children 5-15 years of age were randomized in a double-blind manner to receive either diclofenac 1-2 mg.kg-1 (n=11) or acetaminophen 22.5 mg.kg-1 (n=10). Postoperative pain was assessed by self-report and blood samples were drawn every 30 min for 4 h after medication. RESULTS: Large interindividual differences in maximum plasma diclofenac concentrations (Cmax) were found. Mean Cmax was 2.4+/-1.3 microg.ml-1 and mean tmax was 2+/-0.5 h. No significant reduction in pain score with diclofenac was seen at any of the assessments during the study period. Eight of 10 children achieved Cmax of acetaminophen within the 10-20 microg.ml-1 antipyretic range. Mean tabs was 0.7+/-0.3 h and mean Cmax and tmax were 12.7+/-3.8 microg ml-1 and 1.4+/-0.5 h, respectively. No significant reduction in pain score with acetaminophen was seen at any of the assessments during the study period. CONCLUSIONS: The achieved concentrations of diclofenac and acetaminophen were not able to significantly reduce the children's pain score during the 5 h postingestion study period. Analgesic plasma acetaminophen concentrations may be higher than those required for antipyresis.

Acetaminophen↗
PubMed2001

Response to mivacurium in a patient compound heterozygous for a novel and a known silent mutation in the butyrylcholinesterase gene: genotyping by sequencing.

BACKGROUND: Patients who are homozygous for the atypical mutation, compound heterozygous for atypical and silent mutations, or homozygous for silent mutations (SS) respond to mivacurium with extensively prolonged neuromuscular block. Although important, exact phenotyping of these patients is difficult. This article presents the pharmacodynamics and pharmacokinetics of a normal dose of mivacurium in a patient with phenotype SS, including a pedigree analysis and delineation of the molecular genetic method used to identify the genotype. METHODS: The neuromuscular block following administration of mivacurium, at a dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a mechanosensor and mechanomyography, and times to different levels of recovery were measured. Venous samples for determination of the mivacurium isomers were collected during the interval 134-494 min after administration of mivacurium, and the terminal half-lives were calculated. Butyrylcholinesterase activity, phenotype, and genotype were determined for both the patient and the family. Complete nucleotide sequencing was used to identify the genotype. RESULTS: A train-of-four ratio of 0.75 was reached 469 min after the injection of mivacurium. The terminal elimination half-lives of the mivacurium isomers, cis-trans and trans-trans, were 90 min. Complete nucleotide sequencing revealed two point mutations, the known silent variant S7 and a previously undescribed mutation of amino acid residue 170 introducing a stop codon. CONCLUSIONS: The patient was compound heterozygous for silent mutations in the butyrylcholinesterase gene. The response to mivacurium was an extensively prolonged duration of action. Identification of the rare silent mutations presupposes access to modern molecular genetic methods such as complete nucleotide sequencing.

Adult↗
PubMed2000

Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients.

BACKGROUND: In order to establish an effective drug regimen, we compared the analgesic efficacy of oral diclofenac and high-dose acetaminophen on pain after tonsillectomy. METHODS: In this randomised, double-blind study 48 children, 5 to 15 years of age, following tonsillectomy were assigned to receive either diclofenac 2-3 mg kg(-1) 24 h(-1) (n=24) or acetaminophen 90 mg kg(-1) 24 h(-1) (n=24) for the first three days after surgery. Postoperative pain was assessed by self-report each day before scheduled medication at 7 h, 12 h, 18 h and 23 h. RESULTS: The number of children rating severe pain was high in both the diclofenac group, 5-50%, and in the acetaminophen group, 12-58% during the three day study period. Pain scores in the diclofenac group were only significantly lower at 12 h on day 1-3 compared to pain scores in the acetaminophen group (P<0.05). None of the children in the diclofenac group experienced any episodes of nausea/vomiting compared to 9 children in the acetaminophen group on day 1. The incidences of nausea/vomiting increased with pain (P<0.05). None of the 48 children experienced any episodes of bleeding. CONCLUSIONS: This study indicates that diclofenac was no more effective than high-dose acetaminophen (90 mg vs. 60 mg kg(-1) 24 h(-1)) for analgesia, but resulted in a lower incidence of nausea and vomiting in patients following tonsillectomy.

Acetaminophen↗
PubMed2000

Local infiltration with NSAIDs for postoperative analgesia: evidence for a peripheral analgesic action.

BACKGROUND: In order to investigate the evidence for a peripheral analgesic effect of local infiltration with nonsteroidal antiinflammatory drugs (NSAIDs) in postoperative pain, we conducted a systematic review. METHODS: Randomised controlled and double-blind trials were evaluated. Outcome measures were pain scores, the use of supplementary analgesics, and time to first analgesic request. Efficacy was estimated by significant difference (P<0.05) as reported in the original reports and by calculation of the weighted mean difference of pain scores between treatment groups. RESULTS: Sixteen studies with data from 844 patients were considered appropriate for analysis. The NSAIDs were administered as intra-articular injections, as components of intravenous regional anaesthesia (IVRA), and by wound infiltration and were compared with systemic administration or placebo. In the four studies comparing intra-articular NSAIDs with systemic administration a statistically significant effect in favour of intraarticular NSAIDs was found. Only one study compared IVRA NSAID with systemic administration, showing a significant effect in favour of IVRA administration. No more than two of the five studies comparing intrawound NSAIDs with systemic administration showed significant effect after intrawound administration. Most of the studies comparing local infiltration with placebo showed significant effect in favour of local infiltration. CONCLUSION: There is evidence for a clinically relevant peripheral analgesic action of intra-articular NSAIDs while results of IVRA and wound infiltration with NSAIDs in postoperative pain are inconclusive. Trials without a systemic control group were not considered to provide evidence for a local effect.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Pharmacokinetic studies of neuromuscular blocking agents: good clinical research practice (GCRP).

In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines for good clinical research practice (GCRP) in pharmacokinetic studies of neuromuscular blocking agents is presented. Guidelines include: design of the study; relevant patient groups to investigate; test drug administration, sampling and analysis; pharmacokinetic analysis; pharmacokinetic/pharmacodynamic modeling; population pharmacokinetics; statistics; and presentation of pharmacokinetic data. The guidelines are intended to aid those working in this research area; it is hoped that they will assist researchers, editors of scientific papers, and pharmaceutical companies in improving the quality of pharmacokinetic studies.

Body Temperature↗
PubMed2000

The influence of drug-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.

BACKGROUND: The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium. METHODS: Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography. RESULTS: Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol. CONCLUSION: A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.

Adult↗
PubMed1998

Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy.

BACKGROUND: Tonsillectomy is a common procedure in childhood resulting in significant morbidity due to pain. The aim of this study was to evaluate the analgesic efficacy and safety of a single dose of ketorolac i.v. given before or after tonsillectomy, compared to placebo. METHODS: A randomized, double-blind, placebo-controlled study was performed in 60 children, 5 to 15 years of age, admitted for tonsillectomy. Patients were allocated to receive ketorolac 1 mg.kg-1 i.v. or placebo. Postoperative pain was assessed by self-report 1.5, 3, 5, and 24 h after surgery. RESULTS: Pain scores were significantly lower for both ketorolac groups compared to the placebo group 1.5, 3, and 5 h after surgery (P = 0.05). Pain scores were lowest in the preoperative ketorolac group 1.5 to 5 h after surgery, and significantly fewer children in this group had fentanyl 0 to 1.5 hr after surgery. But no significant differences were found between pain scores of the preoperative and postoperative ketorolac groups in the first 24 h after surgery. Acetaminophen consumption during the first 5 h after surgery was significantly less in patients receiving ketorolac (P < 0.05). Patients in the preoperative ketorolac group had a significantly lower incidence of postoperative vomiting (P < 0.05). There were no significant differences in the incidence of postoperative bleeding between groups. Three children in the preoperative, 5 children in the postoperative ketorolac group and 5 children in the placebo group experienced postoperative haemorrhage. CONCLUSION: This study indicates that a single dose of ketorolac 1 mg.kg-1 i.v. administered either before or immediately after surgery improves postoperative analgesia in children after tonsillectomy without evidence of increased incidence of bleeding.

Acetaminophen↗
PubMed1997

Tracheal administration of atropine in children--effect on heart rate.

Forty-one ASA I patients, aged 2-6 years, anaesthetized for elective ear, nose and throat surgery, were studied in a double blind and randomized fashion in order to examine the effect of tracheally administered atropine 0.02 mg.kg-1 or saline 0.9% on heart rate. In patients receiving atropine heart rate increased 8.8 beats.min-1 (8.7%) and 16.2 beats.min-1 (16.0%) after 3 and 5 min respectively. No increase in heart rate was seen in the saline group. Because of the late onset of action and only moderate increase in heart rate it is concluded that tracheal administration of atropine 0.02 mg.kg-1 to children is insufficient in emergency situations.

Adjuvants, Anesthesia↗
PubMed1996

Specialty practice of family practice residency graduates, 1969 through 1993. A national study.

OBJECTIVE: To describe demographic and practice characteristics of physicians who graduated from family practice residency training programs. DESIGN: Information was obtained from the databases of the American Academy of Family Physicians, the American Board of Family Practice (ABFP), and the American Medical Association. Data sets were cross-referenced, and quantitative data from medical membership organizations and the certifying board were summarized. Information regarding medical school graduation and family practice residency completion was reported by the participating residency programs, and data on practice specialty were self-designated by the participating physicians. SUBJECTS: Physician graduates of Accreditation Council for Graduate Medical Education-accredited family practice residency programs from 1969 through 1993. MAIN OUTCOME MEASURES: Practice specialty designation by graduates of family practice residency programs. RESULTS: Of the 38659 physicians who graduated from family practice residency programs from 1969 through 1993, 8780 (23%) were women, 2181 (6%) were graduates of colleges of osteopathic medicine, 4777 (12%) were international medical graduates, and 33484 (87%) were certified by the ABFP. Of the 36088 family practice residency graduates who designated a practice specialty, 32764 (91%) identified their specialty as family practice, including 32608 physicians who identified family practice, 129 general practice, 21 family practice-geriatric medicine, and six family practice-sports medicine. Among the 3324 family practice residency graduates (9%) who identified themselves as practicing in another specialty, the most common specialties were emergency medicine (1446 physicians [4%]) and preventive medicine (386 physicians [1%]). No other practice specialty was designated by more that 0.5% of family practice residency graduates. CONCLUSION: The vast majority of family practice residency graduates are self-designated as practicing family medicine. These data suggest that family practice residency programs are an effective mechanism for the production of generalist physicians.

Data Collection↗
PubMed1996

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents.

Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.

Clinical Trials as Topic↗
PubMed1995

Dose-response relationship for mivacurium in patients with phenotypically abnormal plasma cholinesterase activity.

During thiopentone-fentanyl-nitrous oxide anaesthesia and using a cumulative design, we studied the dose-response relationship of mivacurium in 8 patients: 7 patients phenotypically homozygous for the atypical plasma cholinesterase gene and 1 patient homozygous for the silent gene. The estimated mean ED50 and ED95 were 15 and 20 micrograms.kg.bw-1 in patients homozygous for the atypical gene, and 13 and 16 micrograms.kg.bw-1 in the patient homozygous for the silent gene, respectively. The results indicate that mivacurium is 4-5 times more potent in patients homozygous for the atypical or the silent gene than in patients with normal plasma cholinesterase activity and phenotype.

Adult↗
PubMed1994

Update on newer neuromuscular blocking drugs.

The development of new non-depolarizing neuromuscular blocking drugs starting with the introduction of the intermediate-acting agents atracurium and vecuronium has made it possible to avoid the use of succinylcholine for elective cases. Recently 4 new drugs have become available; the short-acting mivacurium, the intermediate-acting rocuronium and the 2 long-acting drugs doxacurium and pipecuronium. The pharmacokinetic and pharmacodynamic profile of these drugs are reviewed in this paper.

Adult↗
PubMed1993

Mivacurium-induced neuromuscular blockade in patients with atypical plasma cholinesterase.

The duration of action of mivacurium was evaluated during a modified neurolept anaesthesia in 17 patients heterozygous for the usual and the atypical plasma cholinesterase (pChe) gene (E1uE1a) and in five patients homozygous for the atypical gene (E1aE1a). The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Five heterozygous patients were given a small dose of mivacurium 0.03 mg kg bw-1 intravenously (Group 1). The mean (range) suppression of the first twitch in the train-of-four response (T1) was 91% (69-100%). The time to 90% T1 recovery was 23.9 min (14.0-31.3 min). Twelve other heterozygous patients (Group 2) received mivacurium 0.2 mg kg bw-1 (2.5 x ED95). In these patients the time to 100% T1 suppression was 1.4 min (1.1-2.0 min). The time to reappearance of the T1 response, to 90% T1 recovery, and the recovery index (25.3 min (14.5-34.5), 45.5 min (30.9-59.2), and 9.8 min (6.8-19.6), respectively) were significantly longer than reported in phenotypically normal patients. Five patients homozygous for the atypical gene (Group 3) were given 0.03 mg kg bw-1 mivacurium. The time to reappearance of T1 response following this low dose of mivacurium ranged from 26-128 min. In all five patients the neuromuscular block was successfully antagonized with neostigmine preceded by atropine. In conclusion, mivacurium-induced neuromuscular blockade was moderately prolonged in patients heterozygous for the usual and the atypical gene for plasma cholinesterase. Patients homozygous for the atypical plasma cholinesterase gene appear to be markedly sensitive to mivacurium.

Adolescent↗