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Optimization of the perioperative anaesthetic care for prostate cancer surgery: clinical studies on pain, stress response and immunomodulation
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Prostate cancer (PC) is the most common cancer form in men. Surgery is the treatment of choice for localized form of PC and half of all surgical procedures are radical retropubic prostatectomies (RRP). In the first two studies, we compared the efficacy of thoracic epidural analgesia to patientcontrolled analgesia (PCA) with intravenous morphine (I) and to patientcontrolled local analgesia by intra-abdominal injection of local anaesthetic(LA) (II) in treating postoperative pain after RRP. In studies III and IV we evaluated the effects of thoracic epidural analgesia compared to PCA with morphine in reducing the surgical stress reaction, inflammatory response (III) as well as the immune suppression (IV) following RRP. In studies I and II, we found better pain relief both at rest and on coughing, lower morphine consumption and better respiratory function postoperatively in patients having epidural analgesia. However, we did not register differences in time to home readiness or length of hospital stay. Painmanagement did not significantly affect health-related quality of life. In study III, early surgical stress response (plasma glucose and cortisol) was reduced two hours after the skin incision in patients having epidural analgesia compared with those having intravenous morphine analgesia but no differences in inflammatory mediators were seen except IL-17 which was lower in the epidural group. In study IV, no differences were found between epidural and PCA groups in leucocyte subpopulations, immunecell activation after mitogen stimulation or in natural killer cell cytotoxicityas a measure of innate immunity. We observed a low incidence of side effects and postoperative complications in all studies with no differences between the groups. In summary, thoracic epidural analgesia provided better postoperative pain relief, improved respiratory function and reduction in early stress response to radical retropubic prostatectomy, without any significant effects on inflammation or immune suppression.

Place, publisher, year, edition, pages
Örebro: Örebro universitet , 2012. , p. 97
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 69
Keywords [en]
Radical retropubic prostatectomy, epidural analgesia, patientcontrolled local anaesthesia, patient-controlled analgesia, surgical stress response, local and general inflammatory reaction, immune response
National Category
Medical and Health Sciences Anesthesiology and Intensive Care Surgery
Research subject
Anaesthesiology; Surgery
Identifiers
URN: urn:nbn:se:oru:diva-22804ISBN: 978-91-7668-873-1 (print)OAI: oai:DiVA.org:oru-22804DiVA, id: diva2:526169
Public defence
2012-06-07, Wilandersalen, M-huset, Universitetssjukhuset, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2012-05-10 Created: 2012-05-10 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia
Open this publication in new window or tab >>Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia
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2006 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 105, no 4, p. 784-793Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.

METHODS: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.

RESULTS: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.

CONCLUSIONS: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery.

Place, publisher, year, edition, pages
Wolters Kluwer, 2006
National Category
Medical and Health Sciences Anesthesiology and Intensive Care Surgery
Research subject
Anaesthesiology; Surgery
Identifiers
urn:nbn:se:oru:diva-11124 (URN)000240932400024 ()17006078 (PubMedID)
Available from: 2010-06-16 Created: 2010-06-16 Last updated: 2017-12-12Bibliographically approved
2. Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study
Open this publication in new window or tab >>Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study
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2011 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 107, no 5, p. 782-789Article in journal (Refereed) Published
Abstract [en]

Background.Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA).

Methods.Fifty patients, ASA I–II, participated in this prospective, doubleblinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient- ontrolled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml21 via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h–1 of ropivacaine 1 mg ml–1, fentanyl 2mg ml21, and epinephrine 2mg ml21 epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required.

Results.Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0–10)] compared with Group PCLA [4 (0–10)] (P,0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (P,0.05). Morphine consumption was significantly greater in Group PCLA [12 (0–46)] compared with Group TEA [0 (0–20)] at 0–48 h after operation [median (range)] (P¼0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (P,0.01).Conclusions.TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.

Place, publisher, year, edition, pages
Oxford University Press, 2011
Keywords
anaesthetics local, analgesia epidural, analgesia patientcontrolled, prostatectomy retropubic
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-22946 (URN)10.1093/bja/aer296 (DOI)000295981100019 ()
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2018-05-03Bibliographically approved
3. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response following radical retropubic prostatectomy
Open this publication in new window or tab >>Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response following radical retropubic prostatectomy
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Epidural anesthesia and analgesia has been shown to suppress the neurohormonalstress response in certain types of surgery, but its role in the inflammatory responseto surgery is unclear. The primary aim of this study was to assess whether the choice ofanalgesic technique influences these processes in patients undergoing radical retropubicprostatectomy (RRP).

Method: 26 patients undergoing RRP were randomized to Group P (systemic opioid-basedanalgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction andmaintenance of anesthesia in both groups followed a standardized protocol. The followingmeasurements were made perioperatively : plasma cortisol, glucose, insulin, plasma cytokines(IL-6, TNF-a) and pokeweed mitogen-stimulated cytokines (IFN-g, IL-2, IL-12p70, IL-10,IL-4, and IL-17), C-reactive proteins and leucocyte count. Other parameters recordedincluded pain, morphine consumption and perioperative complications during 72 hours.

Results: Plasma concentration of cortisol and glucose were significantly higher in Group Pcompared to Group E at the end of surgery with a mean difference between groups of 232nmol/L (95% CI 84-381) (P=0.004) and 1.6 mmol/L (95% CI 0.6-2.5) (P=0.003) respectively.No significant differences were seen in any plasma cytokine except IL-17, which was higherin Group P compared with Group E, both at 24 h (P< 0.001) and 72 h (P=0.018)postoperatively. Significantly higher pain intensity was seen up to 24 hours postoperatively inGroup P compared to Group E (p < 0.05).

Conclusion: Thoracic epidural analgesia reduces the early postoperative stress response butnot the acute inflammatory response to radical retrobupic prostatectomy suggesting that otherpathways are involved during the acute phase reaction.

Keywords
radical prostatectomy, stress response, inflammation, epidural, patient controlled, morphine, local anesthetics
National Category
Medical and Health Sciences
Research subject
Medicine; Surgery
Identifiers
urn:nbn:se:oru:diva-22948 (URN)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-10-17Bibliographically approved
4. Early perioperative immunological effects of anesthesia and analgesia in patients undergoing prostate cancer surgery
Open this publication in new window or tab >>Early perioperative immunological effects of anesthesia and analgesia in patients undergoing prostate cancer surgery
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background:Clinical studies in humans as well as experimental evidence from animal studiessuggests that the immune system plays an important role in perioperative metastases following cancer surgery. However, the precise role of the different components of the immune system in this process appears conflicting. Our primary aim was to assess T cell activity and natural killer (NK) cell toxicity in patients undergoing prostate cancer surgery and randomized to epidural or intravenous analgesia.

Methods:26 patients were randomized to receive general anaesthesia and patient controlled analgesia (PCA) with morphine postoperatively (Group P) or combined, general and epidural anaestesia with patient-controlled thoracic epidural analgesia postoperatively (Group E). Blood sample were obtained perioperatively at different time points for analyses of: subpopulations of leukocytes, cell- ediated immune response after mitogen stimulation, NK cell cytotoxicity, vascular endothelial growth factor (VEGF), IFN-g/IL-10 ratio, C-reactive protein (CRP) and white blood cell (WBC) count. In addition, pain and morphine consumtion were also determined.

Results: T lymphocytes decreased more in Group P compared to Group E at 24 hours postoperatively while T-helper lymphocytes decreased more in Group E compared to Group P at the same time point without reaching statistically significant difference.No differences were seen in NK cells or cytotoxic T lymphocytes between the groups. The CD4+/CD8+ ratio remained constant between the groups over time. Natural Killer Cell cytotoxicity did not show statistically significant differences between the groups at the different postoperative time points. No other differences ere found between the groups except in pain intensity which was lower in Group E, and morphine consumption which was greater in Group P. Conclusions:Our findings suggest that regional anaesthesia and analgesia appears to play a minor role in immunomodulation following surgery for prostate cancer. If regional anesthesia does prevent tumour growth or metastases perioperatively, the mechanism for this needs to be further elucidated.

Keywords
patient controlled, thoracic epidural, radical prostatectomy, natural killer cells
National Category
Medical and Health Sciences
Research subject
Medicine; Surgery
Identifiers
urn:nbn:se:oru:diva-22949 (URN)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-10-17Bibliographically approved

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