The effects of pre-emptive epidural sufentanil on human immune function.

BACKGROUND: Surgical stress and general anaesthesia suppress immune functions, including natural killer cell (NK) activity. This suppression could be attributed, at least in part, to the effect of opiates. METHODS: Twenty patients undergoing abdominal hysterectomy received epidural sufentanil (50 microg) either before (pre-emptive) or at the end (control group) of surgery. Post-operative pain relief was provided using sufentanil from a patient-controlled epidural analgesia (PCEA) system. Systemic immunity was assessed by determining leucocyte counts, NK cell counts and activity, lymphocyte response to mitogen stimulation, and secretion of pro-inflammatory cytokines. RESULTS: In the pre-emptive group there was a significant decrease in NK activity on the first and third post-operative day (P < 0.05) compared with baseline values and on the third postoperative day (P < 0.05) compared with the control group. The number of total leucocytes and neutrophiles increased in both groups post-operatively, but no differences were found in the levels of mononuclear lymphocyte populations or in their mitogen responses. Interleukin-6 (IL-6) concentration increased in both groups after the operation. In addition, at the end of the surgery the IL-6 level was greater in the control group than in the pre-emptive group. Interleukin-1 (IL-1) levels had decreased significantly at the end of surgery and 4 h later compared with baseline levels in the pre-emptive, but not in the control group. CONCLUSIONS: Pre-emptive epidural sufentanil during combined propofol and isoflurane anaesthesia had minor effects on the immune response after hysterectomy. The lower production of pro-inflammatory cytokines (IL-1, IL-6) in the pre-emptive group compared with the control group is beneficial, but its clinical importance remains to be determined.

Interscalene brachial plexus block is superior to subacromial bursa block after arthroscopic shoulder surgery.

BACKGROUND: Arthroscopic shoulder surgery is often associated with severe postoperative pain. The results concerning subacromial bursa blockade (SUB) as a method of pain relief have been contradictory. We hypothesized that a SUB and interscalene brachial plexus block (ISB) would similarly reduce early postoperative pain and the need for oxycodone as compared to placebo (PLA). METHODS: Forty-five patients scheduled for arthroscopic shoulder surgery were enrolled in this randomised, prospective study. The ISB and SUB blockades were performed with 15 ml of ropivacaine (5 mg/ml). In the PLA group, 15 ml of 0.9% saline was injected into the subacromial bursa. All patients received general anaesthesia. RESULTS: The mean intravenously patient-controlled delivered oxycodone consumption during the first 6 h was significantly lower in the ISB group (6 mg) than in the SUB group (24.1 mg; P=0.001) or in the PLA group (27 mg; P<0.001). No significant differences were detected between the SUB and PLA groups (P=0.791). The postoperative pain scores during the first 4 h at rest and during the first 6 h on movement were significantly lower in the ISB group than in the SUB and PLA groups. CONCLUSION: After arthroscopic shoulder surgery SUB has a minor effect only on postoperative analgesia, whereas an ISB with low-dose ropivacaine effectively relieves early postoperative pain and reduces the need for opioids.

Pre-emptive effect of epidural sufentanil in abdominal hysterectomy.

BACKGROUND: Experimental studies suggest pre-emptive administration of analgesics is effective but clinical evidence is less convincing. METHODS: Forty-one patients undergoing abdominal hysterectomy were allocated randomly in a double-blind fashion to receive sufentanil 50 micrograms via a lumbar epidural catheter before or at the end of surgery. RESULTS: Sufentanil consumption from a patient-controlled epidural analgesia (PCEA) system and numerical pain scores at rest and during movement over the initial 72 h were similar in the two groups. When the study period was divided into five time intervals, sufentanil consumption in the pre-emptive group was significantly less than in the control group between 8 and 16 h after surgery (P = 0.04). Furthermore, the number of failed bolus attempts from the PCEA device was significantly lower and patient satisfaction was significantly better in the pre-emptive group during the 72 h of PCEA treatment (P < 0.05). In addition, the median decrease in ACTH and cortisol on the first postoperative morning relative to baseline values was greater in the pre-emptive group than in the control group (P < 0.05). In subjects who had a Pfannenstiel incision, touch and pain sensitivity in the wound area were less in the pre-emptive group over the first 4 postoperative days (P < 0.05). CONCLUSIONS: We conclude that pre-emptive analgesia with epidural sufentanil was associated with a short-term sufentanil-sparing effect, and could have reduced stress hormone responses and wound sensitization after abdominal hysterectomy.

Ropivacaine 1 mg x ml(-1) does not decrease the need for epidural fentanyl after hip replacement surgery.

BACKGROUND: Ropivacaine is a new long-acting local anesthetic. Laboratory trials have demonstrated a synergistic analgesic effect between intrathecal opioids and local anesthetics. We tested the hypothesis that addition of ropivacaine 1 mg x ml(-1) to epidural fentanyl (10 microg x ml(-1)) postoperatively decreases the need for fentanyl, improves the quality of analgesia and decreases the side-effects of fentanyl. METHODS: Forty patients were enrolled in this double-blind, randomized study to receive either fentanyl 10 microg x ml(-1) (group F) alone or fentanyl combined with ropivacaine 1 mg x ml(-1) (group R) for 20 h as an epidural infusion at TH12-L1 or L1-L2 for analgesia after hip replacement surgery. The patients were free to use a patient-controlled epidural analgesia device, which was programmed to infuse 3 ml of the study medication hourly and to allow a 3-ml bolus when needed (maximal hourly dose of fentanyl was 150 microg). The consumption of medication, visual pain scores at rest and on movement, hemodynamic and respiratory parameters, motor and sensory block, nausea, pruritus and sedation were recorded. RESULTS: There were no significant differences between the groups in the total mean fentanyl consumption (1.10+/-0.18 mg in group F, 1.08+/-0.31 mg in group R, 95% CI: -0.14 to 0.19, P = 0.774). The pain scores were similar at rest (median scores < or = 1) and on movement (median scores < or = 3). The adverse effects were similar and of a minor nature, consisting mostly of pruritus and nausea. CONCLUSION: Addition of ropivacaine 1 mg x ml(-1) to epidural fentanyl 10 microg x ml(-1) did not significantly decrease the requirement for fentanyl administered for pain relief after hip replacement surgery.

Improving the quality of postoperative pain relief.

A review of the literature shows a constant need to improve the quality of postoperative pain management. The objective of this study was to decrease the intensity and variation of postoperative pain by developing a nurse-based pain service on the ward. An acute pain nurse was appointed and an educational programme with detailed algorithms was started. Regular pain intensity measurements were implemented. Postoperative pain intensity, treatments and side-effects were assessed both before and after the introduction of the new system in 400 patients divided into two consecutive groups of equal size. The number of patients with inadequately treated pain (actual pain > 3/10) dropped by 64% after major gynaecological surgery (25 vs 9%, 95% CI for differences 7-24%; p<0.001 for pain scores). On an average, inadequate pain relief (retrospective average pain > 3/10) on the first postoperative day was more frequent on the ward before than after the reform (47 vs. 21%; 95% CI for differences 15-35%; p<0.001 for pain scores). The incidence of side-effects was similar in both groups (p> 0.05). The intensity and variation of postoperative pain on the ward decreased by developing a nurse-based pain service with an acute pain nurse, an educational programme and regular pain intensity measurements.

Introducing epidural fentanyl for on-ward pain relief after major surgery.

BACKGROUND: Epidural opioids have been recommended for analgesia after major surgery. In this report we describe how we introduced a low-cost, on-ward, nurse-based acute pain service using epidural fentanyl after major surgery in the University Hospitals of Oulu and Kuopio. METHODS: In order to evaluate the feasibility of epidural fentanyl infusion administered by ward nurses, we prospectively assessed pain and side effects during fentanyl infusion (median duration 41 h) after major surgery in 305 consecutive patients in Kuopio. RESULTS: 92% of the patients on the ward who had received epidural fentanyl infusion at 31-54 micrograms h-1 reported at most three episodes of severe pain (/Numerical Rating Scale > 3/ 10) during the initial postoperative days, but there were some patients (8%) who reported several episodes (> 3) of more severe pain (Numerical Rating Scale > 3). Three patients (0.9%) showed a diminished respiratory rate (< 10/min), but only one of them (0.3%) was somnolent. One other patient (0.3%) was not arousable until the cessation of infusion. Nausea and pruritus were minor problems in our patients, but a majority needed a urinary catheter. CONCLUSION: With well-trained nurses, careful monitoring and appropriate protocols, epidural fentanyl infusion proved to be a feasible method for pain relief after major surgery on a surgical ward.

0.1% bupivacaine does not reduce the requirement for epidural fentanyl infusion after major abdominal surgery.

BACKGROUND AND OBJECTIVES: Although local anesthesia has been demonstrated to potentiate spinal morphine analgesia in animal studies, results comparing epidural local anesthesia/opioid mixtures with opioid alone are contradictory in clinical studies. The hypothesis was that, although the concentration of bupivacaine (0.1%) was low to minimize its adverse effects, if the infusion rate of a fentanyl/bupivacaine solution was closely adjusted according to need, the presence bupivacaine would reduce the requirement for epidural fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl (10 micrograms/mL) or a fentanyl/bupivacaine (0.1%) mixture epidurally corresponding to the dermatome of the surgical incision in a double-blind fashion for the first 18 hours after major abdominal surgery. The infusion was titrated for each patient to the rate required for pain relief during forced inspiration (pain score < or = 2, maximum 10). Pain scores, the fentanyl doses required, plasma concentrations of fentanyl at 18 hours, and the incidence and severity of adverse effects were recorded. RESULTS: Patients reported similar median pain scores and were equally satisfied with pain relief in both groups. The mean required post-operative fentanyl infusion rate (57.7 +/- 19.5 micrograms/h) and the plasma concentrations (0.84 +/- 0.36 ng/mL) in the fentanyl group were comparable to the infusion rate (54.4 +/- 19.2 micrograms/h) and the plasma concentrations (0.86 +/- 0.36 ng/mL) in the fentanyl/bupivacaine group. Respiratory and cardiovascular functions were preserved, and the incidence of nausea, pruritus, and periods of drowsiness or sleep were similar in both groups. CONCLUSIONS: In low concentrations (0.1%), bupivacaine did not reduce the titrated dose of epidural fentanyl required for adequate pain relief during forced inspiration after major abdominal surgery. The incidence and severity of adverse effects were also comparable whether or not low-dose bupivacaine infusion was used.

A risk-benefit appraisal of injectable NSAIDs in the management of postoperative pain.

The inadequacy of pain treatment has been demonstrated in many patient groups suffering from acute pain. The injectable nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, diclofenac, ketoprofen and ketorolac, provide relief from the pain associated with several different conditions. When administered alone or in combination with low doses of opioids, NSAIDs provide good pain relief after musculoskeletal trauma or operation. The main advantage of these agents is that they may form the first-line therapy for pain relief and thus decrease the need of opioids. This avoids respiratory depression which can be associated with opioids. In contrast to opioids, NSAIDs do not cause respiratory depression or have marked adverse effects on the central nervous system. However, they may be associated with adverse effects of the gastrointestinal tract, liver and kidneys, and may increase pre- and postoperative bleeding and cause allergic reactions. These effects are related to the ability of NSAIDs to inhibit prostaglandin synthesis. Use of NSAIDs has to be considered carefully in patients with asthma, allergy to aspirin and NSAIDs, atopy, peptic ulcer or bleeding disorders (such as abnormalities in blood coagulation or coagulation deficits). These considerations are especially important in elderly patients. Having taken these contraindications into account, many clinical studies have demonstrated that NSAIDs are at least as safe as opioids when administered in the short term. However, few studies have specifically monitored adverse effects or included patients over 65 to 70 years of age. In addition, patients with risk factors have often been excluded from the trials. Therefore, the risk-benefit ratio of NSAIDs requires further assessment.

Epidural versus intravenous fentanyl for reducing hormonal, metabolic, and physiologic responses after thoracotomy.

BACKGROUND: Previous attempts to prevent all the unwanted postoperative responses to major surgery with an epidural hydrophilic opioid, morphine, have not succeeded. The authors' hypothesis was that the lipophilic opioid fentanyl, infused epidurally close to the spinal-cord opioid receptors corresponding to the dermatome of the surgical incision, gives equal pain relief but attenuates postoperative hormonal and metabolic responses more effectively than does systemic fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl epidurally and saline intravenously, or fentanyl intravenously and saline epidurally, in a double-blind fashion for the first 20 h after thoracotomy. For each patient, the fentanyl infusion was titrated to the rate required for pain relief (pain score < 3, maximum 10). Postoperative changes in blood pressure, heart rate, rectal temperature, and blood concentrations of adrenocorticotrophic hormone, beta-endorphin immunoreactivity, cortisol, growth hormone, prolactin, glucose, and leukocytes were assessed. RESULTS: Patients reported similar median pain scores, but the epidural group required about 40% less fentanyl than the intravenous group. Four hours postoperatively, the beta-endorphin immunoreactivity concentrations were less in the epidural than in the intravenous group. Plasma cortisol increased in a similar manner in both groups within 4 h of surgery, but the increase persisted to the next morning only in patients receiving intravenous fentanyl. Adrenocorticotropin, growth hormone, and prolactin responses were similar in both groups. The postoperative hyperglycemic response, leukocytosis, and blood pressure were greater, and mean rectal temperature was lower, in the intravenous than in the epidural fentanyl group. CONCLUSIONS: The authors' results indicate that some aspects of the hormonal response to surgery are blocked more completely with epidural than with intravenous fentanyl. Adequate pain relief with epidural fentanyl, with a smaller mean dose, led to a smaller increase of some hormonal, metabolic, and physiologic responses after thoracotomy than in association with the adequate pain relief provided by intravenous fentanyl.

A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy.

This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy, in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion. Forty patients were assigned randomly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion. For each patient the fentanyl infusion was titrated to a rate required for pain relief (pain score less than 3, maximum 10). Patients reported similar median pain scores, but in the epidural group the required mean fentanyl infusion rate was less (0.95 +/- 0.23 vs. 1.67 +/- 0.46 micrograms.kg-1.h-1, P = 0.0001) and plasma fentanyl concentrations were less at 4 and 18 h (4 h: 0.81 +/- 0.27 vs. 1.38 +/- 0.36 ng.ml-1, P = 0.0001; 18 h: 0.94 +/- 0.32 vs. 1.54 +/- 0.65 ng.ml-1, P = 0.0007) than those in the intravenous group. Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group. In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy.