Pain relief and safety after major surgery A prospective study of epidural and intravenous analgesia in 2696 patients. Link to publication Citation for published version (APA): Flisberg, P., Rudin, Å., Linnér, R., & Lundberg, C. J. F. (2003). Pain relief and safety after major surgery A prospective study of epidural and intravenous analgesia in 2696 patients. Acta Anaesthesiologica Scandinavica, 47(4), 457-465. DOI: 10.1034457-465. DOI: 10. /j.1399457-465. DOI: 10. -6576.2003 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Background: Adverse effects may still limit the use of continuous epidural and intravenous analgesia in surgical wards. This study postulated that postoperative epidural analgesia was more efficient, and had fewer side-effects than intravenous morphine. The aim was to investigate efficacy, adverse effects and safety of the treatments in a large patient population. Methods: During a five-year period 2696 patients undergoing major surgery, received either epidural or intravenous analgesia for postoperative pain relief. The patients were prospectively monitored in surgical wards. Pain was evaluated with a numeric rating scale (0Ð10) at rest/mobilization. Treatment duration, respiratory depression, sedation/hallucinations/ nightmares/confusion, nausea/vomiting, pruritus, orthostatism/ leg weakness, and insufficient pain relief were registered. Pain relief for all patients aimed at a pain scoring of less than 4 at rest. Results: Epidural analgesia was used in 1670 patients, and intravenous morphine in 1026 patients. Patients with epidural analgesia experienced less pain both at rest and during mobilization. Insufficient treatment effects such as dose adjustments, orthostatism/leg weakness, and pruritus were more common in the epidural group. Respiratory depression and sedation/hallucinations/nightmares/confusion occurred more often in the intravenous group. Thoracic epidural catheters caused a lower incidence of motor blockade compared to lumbar catheter placements. Conclusion:In a large patient population the use of epidural and intravenous postoperative analgesia was considered safe in surgical wards, and the incidence of adverse effects was low.Patients with epidural analgesia experienced overall less pain, while opioid related side-effects were more common with intravenous morphine analgesia.

AimsIn experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. MethodsPatients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. ResultsThe area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue ( P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T max were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T max value tended to be shorter in 'worse' brain tissue. ConclusionsThe unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.

Background: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. Methods: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. Results: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). Conclusions: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.

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