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Early bioavailability of paracetamol after oral or intravenous administration
Department of Cardiothoracic Surgery and Anesthesiology Karolinska University Hospital S-171 76 Stockholm.
2004 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, ISSN 0001-5172, Vol. 48, no 7, 867-870 p.Article in journal (Refereed) Published
Abstract [en]

Background:  Paracetamol is a peripherally acting analgesic commonly used in multimodal post-operative pain management to reduce the need for more potent analgesics with their unwanted side-effects. The dose and optimal galenical form for achieving analgesic concentrations is not well defined. The primary aim of this pilot project was to study the early bioavailability for two fixed doses of orally administrated paracetamol and one dose of intravenous propacetamol, all of which were given after minor surgery.

Methods:  Thirty-five patients undergoing day surgery were divided into five groups, seven patients each. Groups received either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma concentration of paracetamol during the first 80 min after administration.

Results:  Within 40 min, intravenous propacetamol gave a median plasma paracetamol concentration of 85 µmol/l (range 65–161) and decreased thereafter. After oral administration, median plasma paracetamol concentration increased with increasing dose and time, but there were huge inter-individual differences at all time points studied. At 80 min after oral paracetamol the median plasma concentrations were 36 and 129 µmol/l for the 1- and 2-g groups, respectively, with an overall range between 0 and 306 µmol/l.

Conclusion:  Oral administration of paracetamol as part of multimodal pain management immediately post-operatively resulted in a huge and unpredictable variation in plasma concentration compared with the intravenous administration.

Place, publisher, year, edition, pages
2004. Vol. 48, no 7, 867-870 p.
Keyword [en]
bicarbonated formula, intravenous propacetamol, pain management, paracetamol, post-operative analgesia
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:rkh:diva-357DOI: 10.1111/j.0001-5172.2004.00452.xOAI: oai:DiVA.org:rkh-357DiVA: diva2:552703
Available from: 2012-09-15 Created: 2012-09-15 Last updated: 2014-07-08Bibliographically approved
In thesis
1. Pain treatment after surgery: With special reference to patient-controlled analgesia, early extubation and the use of paracetamol
Open this publication in new window or tab >>Pain treatment after surgery: With special reference to patient-controlled analgesia, early extubation and the use of paracetamol
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The introduction of general anaesthesia eliminated pain during surgical operations. After surgery, however, pain and postoperative nausea and vomiting (PONV) have remained a persistent problem for many patients. The need for analgesics varies widely among patients, therefore standardised treatment protocols are often insufficient pain treatment. Our studies dealt with the incidence and severity of pain and PONV after cardiac surgery. Study aims were to use and develop techniques for better evaluation of analgesic needs – visual analogue scale (VAS; 0 to 10) – and to develop a multimodal treatment of pain with opioids administered by the patients themselves – Patient Controlled Analgesia (PCA) – combined with paracetamol. In 48 patients, PCA was compared to conventional Nurse Controlled Analgesia (NCA) on the ward after coronary artery bypass surgery. PCA led to lower VAS-scores, i.e. less pain, with the use of more opioids. In 57 patients, pain after heart surgery was compared for extubation “early” at 3 hours or “late” at 7 hours after surgery. VAS-scores, PONV and the amount of opioids used were similar whether patients were extubated early or late. Rectal and intravenous (i.v.) administration of paracetamol was compared in 28 patients after heart surgery with respect to its bioavailability after repeated doses. Plasma concentrations after the first dose were low with rectal administration. After the fourth dose at 24 hours they reached a plateau. With i.v. administration concentrations were higher both after the first and fourth dose. Oral and i.v. paracetamol was compared in 80 patients after heart surgery and in 35 patients after day surgery (hernia repairs etc). After heart surgery the use of opioids was less in the i.v. group but VAS-scores and PONV were similar. A majority of the patients scored higher than 3 once or more than once on the 10 degree VAS-scale. In the oral group after day surgery, the plasma concentration increased in a dose-dependent manner but the scatter was wide and unpredictable as compared to the i.v. group. Conclusions: PCA is a promising alternative to NCA for adequate pain treatment in the wards after heart surgery and is “by itself” adjusted to the needs of the individual patient. There is no risk that early extubation after cardiac surgery is followed by more postoperative pain. Intravenous paracetamol seems to have an opioid-sparing potential after heart surgery. Our routines must be further developed and more studies are needed to find an optimal regimen, since pain treatment sometimes was insufficient in many patients receiving the combined therapy.

Place, publisher, year, edition, pages
Stockholm: Repro Print, 2004. 50 p.
Keyword
acetaminophen, analgesia, patient-controlled, analgesics, day surgery, heart surgery, opioid, ketobemidone, pain measurement, pain, postoperative, paracetamol, postoperative nausea and vomiting, visual analogue scale
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:rkh:diva-715 (URN)91-7140-134-2 (ISBN)
Public defence
2004-12-17, Thoraxklinikens aula, Karolinska Universitetssjukhuset, Stockholm, 09:00
Available from: 2014-07-08 Created: 2013-09-03 Last updated: 2014-07-08Bibliographically approved

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