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Biomedical subjects

A Tamsen

Publications and source records attributed to A Tamsen.

At least 37 records · Page 2Linked to original sources
PubMed1988

Patient-controlled analgesia with extradural morphine or pethidine.

Two groups of patients were allowed to self-administer morphine (n = 17) or pethidine (n = 15) extradurally after abdominal surgery, for a mean period of 16 h. Bolus increments of morphine 1 mg or pethidine 20 mg were administered by programmable pump. Pain relief from extradural patient-controlled analgesia (PCA) was excellent in all but two patients in the morphine group. Pain relief was not qualitatively different between the two groups. No clinical respiratory depression was seen. The average consumption of extradural morphine was 0.52 +/- 0.29 mg h-1 (range 0.19-1.04 mg h-1) and of pethidine 18.0 +/- 8.1 mg h-1 (5.8-35.4 mg h-1). This yields an equianalgesic dose relationship of 1:35. Morphine consumption was more irregular than pethidine consumption. Morphine and pethidine plasma concentrations measured during PCA were well below the reported minimum analgesic plasma concentrations in most cases. Several patients, particularly in the pethidine group, tended to increase their opioid consumption during PCA. This could be explained by an increasingly smaller fraction of the pethidine bolus being absorbed to the subarachnoid space during frequent repetitive dosing. The large inter-individual variation in consumption makes it impossible to recommend a standard dose of extradural morphine or pethidine for analgesia of predictable duration and with a minimum of adverse effects.

Adult↗
PubMed1988

Cerebrospinal fluid concentrations of substance P and (met)enkephalin-Arg6-Phe7 during surgery and patient-controlled analgesia.

The possible role of two neuropeptides (substance P and (Met)enkephalin-Arg6-Phe7) in nociception were studied in 14 surgical patients. Lumbar cerebrospinal fluid (CSF) concentrations of the putative excitatory afferent transmitter substance P and the mu and delta receptor agonist (Met)enkephalin-Arg6-Phe7 were measured during general anesthesia for abdominal surgery and during the postoperative period when patient-controlled analgesia (PCA) was used for control of pain. The CSF was sampled through an intrathecal catheter. Seven of the patients were randomly assigned to receive neurolept anesthesia; the rest were given isoflurane anesthesia without narcotics. No statistically significant changes occurred in substance P concentrations in CSF during surgery or postoperative PCA, nor were there significant differences between the two groups. There was, however, a significant correlation between CSF substance P concentrations before the start of PCA and pain assessment on a visual analogue scale. The individual changes in substance P concentrations during PCA was also inversely correlated to the consumption of meperidine. The CSF (Met)enkephalin-Arg6-Phe7 concentrations were below the level of detection in seven of the patients before anesthesia. A large interindividual variability in both substance P and (Met)enkephalin-Arg6-Phe7 concentrations was evident. The absence of major changes in CSF neuropeptide concentrations was unexpected. Apparently inter-individual variations in neuropeptide output are considerable.

Adult↗
PubMed1987

Pharmacokinetics of midazolam in total i.v. anaesthesia.

The pharmacokinetics of midazolam during total i.v. anaesthesia were determined in 15 female patients undergoing major surgery. Midazolam was administered together with an analgesic drug and a neuromuscular blocking drug. The dose regimen of midazolam, based on simulations, included two consecutive infusions following a bolus injection at the induction of anaesthesia. Multiple blood samples were drawn and a two-compartment open model was fitted to the measured plasma concentrations. Plasma clearance (483 ml min-1), apparent volume of distribution (1.94 litre kg-1) and terminal half-life (3.1 h) were in agreement with other reports. Thus, there was no obvious evidence that the surgical procedure or the concomitant use of other drugs, or both, influenced the pharmacokinetics of midazolam. The relatively rapid elimination makes midazolam suitable for use by infusion in a total i.v. technique.

Adult↗
PubMed1987

Pharmacokinetics of epidural morphine and meperidine in humans.

Five groups of surgical patients, each comprising six individuals, received epidural doses of morphine or meperidine, and the plasma and CSF kinetics were studied. Three groups received epidural doses of morphine 3 mg in 1 or 10 ml or meperidine 30 mg in 1 ml. Cerebrospinal fluid (CSF) and central venous blood opioid concentrations were measured intermittently for 6 h after injection. Two groups received epidural doses of morphine 3 mg in 1 ml or meperidine 30 mg in 1 ml, and opioid CSF concentrations were determined over a 24-h period. Morphine appeared rapidly in plasma, and maximum plasma concentrations were usually detected 5 min after injection and averaged 33 ng.ml-1 in the 1-ml volume group and 40 ng.ml-1 in the 10-ml volume group. The terminal plasma half-life averaged 91 +/- 34 min and 87 +/- 27 min, respectively (mean +/- SEM). Maximal plasma concentrations of meperidine were usually detected 10 or 15 min post-injection and averaged 196 +/- 29 ng.ml-1. The terminal plasma half-life averaged 124 +/- 26 min. Morphine crossed the dura relatively slowly, and the absorption half-life across the dura averaged 22 min. Maximal CSF concentrations were usually seen 60-90 min post-injection. In contrast, meperidine crossed the dura quickly, with an absorption half-life averaging 7.6 +/- 2.0 min. Maximal CSF concentrations were seen 15 or 30 min post-injection. Morphine and meperidine concentrations remained several times higher in the CSF than in the plasma. The fraction of the opioid dose crossing the dura was calculated to be 3.6% for morphine and 3.7% for meperidine. There were no significant differences in the kinetics of morphine administered in 1 or in 10 ml when CSF was sampled close to the site of lumbar epidural injection. The CSF concentration-time curves of both drugs decreased biexponentially after the initial rise due to diffusion across the dura. The early half-life in CSF averaged 73.3 +/- 11.5 min for morphine and 71.3 +/- 3.1 min for meperidine, and the late half-life averaged 369 +/- 113 min for morphine and 982 +/- 449 min for meperidine. Dose-normalized morphine and meperidine CSF concentrations after epidural administration showed that meperidine concentrations were down to one-fourth the corresponding morphine concentrations from the 2nd to the 15th h after administration, which may partly explain the longer duration of analgesia from morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Pharmacokinetics of intrathecal morphine and meperidine in humans.

Two groups of surgical patients each comprising six individuals received an intrathecal injection of morphine 0.3 mg or meperidine 10 mg. Cerebrospinal fluid (CSF) and plasma were sampled frequently during a 6-h period and analyzed for morphine or meperidine. Maximum plasma morphine concentrations were found 5-10 min after injection, and averaged 4.5 +/- 1.1 ng.ml-1 (mean +/- SEM). Maximum CSF morphine concentrations were considerably higher than maximum plasma concentrations, 6410 +/- 1290 ng.ml-1. Maximum plasma concentrations of meperidine were also measured 5 or 10 min after injection and were low (36 +/- 9 ng.ml-1) compared with the maximum CSF concentrations (364 +/- 105 micrograms.ml-1). After a rapid initial decline for about 15 min after injection, the CSF concentrations decreased with a half-life of 89.8 +/- 16.1 min for morphine and 68.0 +/- 5.1 min for meperidine during the rest of the study period. The initial volume of distribution in CSF was similar for both drugs, or 22 +/- 8 ml for morphine and 18 +/- 5 ml for meperidine. After 6 h, 1.6 +/- 0.9% of the injected morphine dose and 0.41 +/- 0.09% of the meperidine dose remained in the initial volume of distribution. Large inter-individual differences in morphine and meperidine CSF kinetics existed, which may explain some of the reported individual differences in duration of effects. The disappearance of meperidine from CSF tended to be faster than that of morphine, which may be explained, in part, by the differences in lipid solubilities of the drugs.

Adult↗
PubMed1987

Atracurium infusion in total intravenous anesthesia.

The neuromuscular blocking effect of atracurium given as a bolus dose (0.5 mg X kg-1) followed by a maintenance infusion was studied during two different anesthetic techniques. It has been reported that benzodiazepines interact with non-depolarising neuromuscular blockers. In this study no difference was found in the effect of atracurium given with conventional fentanyl/nitrous oxide anesthesia when compared to total intravenous anesthesia using midazolam/alfentanil. More than 90% twitch depression was achieved after 123 and 137 s, respectively. Recovery time to 10% twitch height following the bolus dose was around 32 min. The dosage range for atracurium given by infusion (0.29-0.44 mg X kg-1 X h-1) was confirmed.

Adult↗
PubMed1986

Midazolam-fentanyl anesthesia for major surgery. Plasma levels of midazolam during prolonged total intravenous anesthesia.

The water-soluble benzodiazepine midazolam was used along with fentanyl and pancuronium in a totally intravenous anesthetic technique for hysterectomies. Midazolam was given as a 0.3 mg X kg-1 bolus dose followed by constant rate infusion of 0.25 mg X kg-1 X h-1. Plasma midazolam concentrations were measured during the anesthesia. The technique provided excellent conditions for surgery, with pulse rate and blood pressure under good control and without any recall of the peri-operative period. A disadvantage was early respiratory depression, which necessitated administration of naloxone to make extubation possible. This was attributed to the proportionally large amount of fentanyl used. Drowsiness during the first postoperative hours was also pronounced.

Adult↗
PubMed1982

Endorphins and the modulation of acute pain.

The endorphins constitute a large family of structurally but not generically related peptides. They act pharmacologically like narcotic analgesics. An intimate connection between endorphin fibers and pain pathways is present, for instance, at the spinal level and at the first synapse of primary afferent pain fibers. These fibers may contain the neuropeptide substance P. In acute pain, naloxone injection causes a significant increase in pain suffering. A patient with high preoperative endorphin levels in the cerebrospinal fluid will require less pethidine for adequate pain relief after major abdominal surgery. Pethidine administration reduces substance P levels in the cerebrospinal fluid. The data suggest that endorphins do not have a protective role in acute pain conditions.

Acupuncture Therapy↗
PubMed1982

Pharmacokinetics of pethidine during anaesthesia and patient-controlled analgesic therapy.

The pharmacokinetics of pethidine has been studied in 12 patients subjected to major intraabdominal surgery. Pethidine and norpethine were analyzed in plasma samples collected during anesthesia and during patient-controlled administration of small intravenous doses of pethidine in the early postoperative period. A second study on the pharmacokinetics of pethidine was performed on the 3-5th postoperative day. The plasma clearance of pethidine was significantly lower in the preoperative study (8.9 +/- 1.8 ml x kg x min-1) compared with the postoperative study (12.0 +/- 3.1 ml x kg x min-1). Volume of distribution (Vd) was not significantly influenced, being 4.25 +/- 1.72 l x kg-1 peroperatively and 3.14 +/- 0.84 l x kg-1 postoperatively. Elimination half-life decreased from 5.91 +/- 3.57 h peroperatively to 3.25 +/- 1.40 h postoperatively. The kinetics of pethidine in the postoperative study agreed with pethidine kinetics reported for healthy volunteers. The fraction of unbound pethidine decreased from 0.26 +/- 0.1 peroperatively to 0.18 +/- 0.1 postoperatively. Norpethidine, a metabolite of pethidine, has been claimed to be responsible for several side effects like respiratory depression and convulsions during pethidine therapy. No side effect attributable to norpethidine was observed in the self-administration period. Norpethidine plasma concentrations did not exceed 500 ng/ml. The altered pethidine pharmacokinetics during anesthesia and the ensuing postoperative hours and the interindividual differences of the disposition of the drug strongly suggest that pethidine should be given by individualized regimens in surgical patients.

Anesthesia↗
PubMed1982

Multiple dose kinetics of ketobemidone in surgical patients.

Twelve patients scheduled for major abdominal surgery were selected for a study of the kinetics of ketobemidone during the day of surgery and in a follow-up study 3-5 days after surgery. In six patients ketobemidone was administered as ketobemidone plain and in the other six, it was given as Ketogin, a combination formula containing a spasmolytic substance in addition to ketobemidone. Plasma samples were collected for approximately 24 h following induction of anesthesia, during which time multiple doses of ketobemidone were administered. A single-dose study was performed 3-5 days after surgery using the same drug. No significant differences were found between the two formulations of ketobemidone. Plasma clearance did not change significantly between the two periods of study, being 18.0 +/- 4.4 ml . kg-1 . min-1 peroperatively and 21.7 +/- 7.6 ml . kg-1 . min-1 postoperatively. Peroperative Vd area was significantly larger than post-operative Vd area, 5.84 +/- 2.62 l . kg-1 and 3.63 +/- 0.38 l . kg-1, respectively. T1/2 terminal decreased from 3.84 +/- 1.6 h peroperatively to 2.06 +/- 0.44 h postoperatively.

Analgesics, Opioid↗
PubMed1982

Patient-controlled analgesic therapy: clinical experience.

Fifty-six surgical patients self-administered i.v. narcotic analgesics to combat postoperative pain. Analgesic demand per h was 2.7 +/- 1.1 mg of morphine, 26 +/- 10 mg of pethidine or 2.3 +/- 0.8 mg of ketobemidone, which reflects the equianalgesic ratios. Acute respiratory depression was seen in two hypovolaemic patients as evidenced by a raised PaCO2 on air breathing. Carbon dioxide retention disappeared upon correction of hypovolaemia. Late respiratory complications of short duration were encountered in 13%. Drowsiness and dry mouth were the most frequent complaints. Self-administered analgesia was considered highly satisfactory by the patients.

Adult↗
PubMed1979

Patient controlled analgesic therapy in the early postoperative period.

Fourteen patients with postoperative pain were allowed to self-administer preset doses of pethidine intravenously via a logic-controlled motor syringe. Plasma samples were collected during anaesthesia and the postoperative self-administration period, and the concentrations of pethidine and nor-pethidine were determined. Separate single-dose studies in eight patients yielded pharmacokinetic parameters which made possible computer simulations of continuous plasma concentration curves for the anaesthesia and postoperative self-administration period. The consumption of pethidine showed great interindividual variations with a mean consumption for the entire group of 26 mg per hour. The patients established steady-state plasma concentrations with far less than the maximum amount of pethidine allowed. The mean measured plasma concentration of pethidine which provided adequate analgesia was 738 +/- 149 ng/ml. Simulated and measured plasma concentrations were in close agreement. The individual mean drug consumption per hour during self-administration correlated closely with the individual elimination rate of pethidine. No serious side effects were observed. Thus, patient-controlled analgesic therapy offers an individualized analgesic supply to meet an analgesic demand which is governed by each patient's appreciation of pain.

Adult↗
PubMedDate not supplied

Patient-controlled analgesic therapy. Part I: Pharmacokinetics of pethidine in the per- and postoperative periods.

The influence of anaesthesia and surgery on the pharmacokinetics of pethidine (meperidine) was studied in 12 patients. Plasma pethidine concentrations in central venous blood collected during anaesthesia and the ensuing postoperative hours were by gas chromatography with electron capture detection. Postoperative analgesia was accomplished by patient-controlled intravenous administration of small doses of pethidine. The NONLIN program was used to calculate pharmacokinetic parameters for each individual. A single dose study of pethidine kinetics was carried out in all patients 3 to 5 days postoperatively. Mean +/- SD for peroperative Vd area was 4.3 +/- 1.7L/kg and for the elimination half-life was 6.1 +/- 3.6h. In the postoperative period Vdarea was 3.2 +/- 0.8L/kg and the elimination half-life was 3.2 +/- 1.4h. Plasma clearance increased from a peroperative value of 8.9 +/- 1.9 ml/min/kg to a postoperative value of 12 +/- 3.0 ml/min/kg. The changes in elimination half-life and plasma clearance are significant. The postoperative pharmacokinetics of pethidine were in accordance with those reported for healthy volunteers. The fraction of unbound pethidine was significantly reduced postoperatively - from 0.26 +/- 0.10 (peroperatively) to 0.18 +/- 0.10 (3 to 5 days later).

Adult↗