Geir Niemi

Adrenaline markedly improves thoracic epidural analgesia produced by a low‐dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double‐blind, cross‐over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture.

Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine, fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized, double-blinded crossover study with and without epinephrine.

We have shown that epinephrine markedly improves the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl. Ropivacaine has an intrinsic vasoconstrictive effect, and epinephrine may therefore not have the same pharmacokinetic interaction in a ropivacaine-fentanyl infusion; but a possible spinal cord &agr;2-agonist effect of epinephrine would give the same positive pharmacodynamic interaction with ropivacaine and fentanyl during epidural analgesia. In a prospective, randomized, crossover study, a thoracic epidural infusion of ropivacaine 1 mg/mL and fentanyl 2 &mgr;g/mL with or without epinephrine 2 &mgr;g/mL was given to 12 patients in a double-blinded manner after major thoracic or upper abdominal surgery. Main outcome measures were pain intensity at rest and when coughing, evaluated on a visual analog scale. Extent of sensory blockade was evaluated by determining dermatomal hypoesthesia to cold. Pain increased (P < 0.001) and hypoesthetic dermatomal segments decreased (P < 0.001) when epinephrine was omitted from the triple epidural infusion. After 3 h without epinephrine, pain intensity when coughing was unacceptable despite rescue analgesia. After restarting the triple epidural mixture with epinephrine, pain was again reduced to mild pain when coughing, and the sensory blockade was restored. The mixture with epinephrine caused less nausea and facilitated mobilization. We conclude that epinephrine improves the pain relief and reduces the side effects of a thoracic epidural infusion of ropivacaine and fentanyl after major thoracic or upper abdominal surgery.

Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects

Background:  In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well‐established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day.

The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine, fentanyl and adrenaline after major surgery A randomized, double-blind, dose-finding study.

Background: We have documented that adrenaline 2.0 µg·ml− 1 markedly improves relief of dynamic pain when added to a thoracic epidural analgesic infusion of bupivacaine 1 mg·ml− 1 and fentanyl 2 µg·ml− 1. Concern about possible adverse effects on spinal cord blood flow, expressed by others, prompted us to find the lowest concentration of adrenaline needed to produce effective and reliable pain relief after major surgery.

Epidural fentanyl markedly improves thoracic epidural analgesia in a low-dose infusion of bupivacaine, adrenaline and fentanyl: A randomized, double-blind crossover study with and without fentanyl

Background: The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief, and side effects when removing fentanyl from an optimally titrated epidural infusion consisting of bupivacaine, fentanyl and adrenaline.

2 Safe and effective post-operative pain relief: introduction and continuous quality-improvement of comprehensive post-operative pain management programmes

Summary Planning and implementing a comprehensive, hospital-wide post-operative pain management programme in two university hospitals started in 1992 with emphasis on patient safety and implementing patient-controlled intravenous morphine analgesia and epidural analgesia with a low dose bupivacaine, fentanyl and adrenaline analgesic mixture on ordinary wards as focus for improving quality of post-operative pain management. A major educational programme for all personnel involved in the care of surgical patients aimed at improving understanding of post-operative pain, the consequences of unrelieved pain and increased general knowledge of pain relieving drugs and methods. Gradual, ward-by-ward introduction of PCA and epidural analgesia, with individual follow-up of nurses and patients by the specially assigned anaesthesiologist and nurse, selection of electromechanically very safe pain pumps, standardized prescription and monitoring regimen, has resulted in good to excellent patient satisfaction in 90% of 5749 patients. Side effects reduced quality of pain relief or caused early discontinuation of PCA and epidural analgesia in 25% of patients during the early phase of the programme, later 10–15%. Nausea, dizziness, sedation, confusion, pruritus, and urinary retention were the most frequent adverse effects during PCA. These were infrequent or mild during epidural analgesia, but epidural catheter-problems occurred in 15–20% of patients. Epidural catheter problems have improved, but continue to cause failure or premature discontinuation in 10–15% of epidural analgesia patients. No serious complications with permanent adverse outcome occurred. Four patients had potentially serious respiratory depression in 2922 PCA patients during 11 380 PCA-patient-days due to human error, three potentially serious complications in 2827 epidural patients during 14 870 epidural-patient-days, all were discovered early and treated successfully. These results demonstrate clearly that the infrastructure, the educational and quality assurance programmes of our post-operative pain management concept, are both effective and safe. The economic cost of equipment, medication, and wages for the personnel assigned to the programme are modest when we consider that most surgical patients benefit from the comprehensive post-operative pain management programme. Although we have not attempted to document reductions in post-operative complications or in duration of post-operative course, it is plausible that there is an overall net saving in health care cost from the post-operative pain management programme.

Adding propacetamol to ketorolac increases the tolerance to painful pressure.

Combining an NSAID and paracetamol (acetaminophen) has in some studies given superior analgesia compared with the single drugs. In other trials no additive effect has been found. We have investigated the effect of this drug combination on the pressure pain tolerance threshold (PPTT), a reproducible correlate to clinical pain.

6 Optimal epidural analgesia: importance of drug combinations and correct segmental site of injection

Summary Our experience during almost 20 years with various epidural analgesia regimes and a review of published studies attempting to assess the role of epidural drug combinations and spinal-segmental site of injection, indicate the following. 1. The hydrophilic morphine is insensitive to the segmental site of injection and may be given in the lumbar epidural area for thoracic pain. Morphine causes a high incidence of nausea, pruritus and urinary retention. With an epidural infusion of less than 200 μg/hour the risk of respiratory depression is probably not higher than with other epidural opioids. 2. The lipophilic opioids (fentanyl, sufentanil, diamorphine) are absorbed rapidly into the epidural vasculature. When given epidurally in doses that are high enough for systemic analgesic effect, fentanyl and sufentanil are no more effective than when administered intravenously. Such high lumbar epidural doses will also affect thoracic pain through the systemic effects. 3. Dilute concentrations and addition of adrenaline impede systemic absorption and improve selective spinal analgesic effects of epidural fentanyl and sufentanil. When applied at a segmental level appropriate for the surgery, low-dose fentanyl and sufentanil are more effective than when given intravenously. 4. Low doses of local anaesthetics have a selective spinal cord analgesic effect that synergizes with the spinal analgesic effect of opioids. 5. Adrenergic agonists cause a selective spinal cord analgesia that synergizes with the analgesic effects of opioids and local anaesthetics. 6. The systemic effects of epidural clonidine cause hypotension and sedation. 7. Adrenaline has beneficial effects on the pharmacokinetics of epidural lipophilic opioids and local anaesthetics, reducing their absorption into the epidural vasculature. This reduces systemic side effects and enhances the spinal analgesic effects of opioids and local anaesthetics. 8. Thus, epidural analgesia is best obtained, with the lowest dose and least side effects, by infusing a low-dose combination of each of these three classes of drugs at a spinal cord segment level appropriate for the site of surgery. 9. We have obtained optimal post-operative analgesia with epidural fentanyl (mean: 14–16 μg/hour) in combination with bupivacaine (mean: 7–8 mg/hour and adrenaline (mean: 14–16 μg/hour) in 90% of more than 3000 patients when the infusion was given at an appropriate, site-specific segmental level (epidural catheter tip above L2). This gave satisfactory analgesia without motorneurone blockade and leg weakness. The total amount of fentanyl needed was so low that nausea and pruritus were insignificant problems. Respiratory depression and hypotension did not occur. However, one patient had an erroneous prescription for fentanyl 100 μg bolus-injections and developed respiratory depression. 10. Epidural catheter problems continue to be obstacles to perfect epidural analgesia. Too low epidural catheter placement or lateral catheter-tip position caused failure in 5–8% with insufficient analgesia and/or leg weakness. In another 5–9%, later displacement of the epidural catheter, disconnections, or entry-site skin infection caused discontinuation of epidural analgesia one or more days earlier than planned. 11. A high degree of vigilance and routine monitoring by well educated nurses on surgical wards of possible epidural catheter complications such as epidural infection, haematoma or catheter migration is mandatory for safe epidural analgesia practice on surgical wards. In 3000 patients receiving epidural post-operative analgesia on surgical wards for about 15 000 patient-days, we have observed only three potentially dangerous complications (one patient had erroneous fentanyl bolus-injection with consequent respiratory depression and two patients had epidural infections), detected early and treated successfully without permanent patient damage. These results testify to the efficacy and safety of our triple-component, low-dose, and site-specific epidural infusion analgesia regimen for post-operative pain relief after major surgery.

Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl

Background: A low dose solution of adrenaline 2 μg · ml−1, fentanyl 2 μg · ml−1 and bupivacaine 1 mg · ml−1 has been reported to give superior pain control when used for epidural analgesia after major surgery. The present paper describes the compounding and chemical stability of this triple‐component solution during storage and use.

The Shamrock lumbar plexus block: A dose-finding study

BACKGROUND The Shamrock technique is a new method for ultrasound-guided lumbar plexus blockade. Data on the optimal local anaesthetic dose are not available. OBJECTIVE The objective of this study is to estimate the effective dose of ropivacaine 0.5% for a Shamrock lumbar plexus block. DESIGN A prospective dose-finding study using Dixons up-and-down sequential method. SETTING University Hospital Orthopaedic Anaesthesia Unit. INTERVENTION Shamrock lumbar plexus block performance and block assessment were scheduled preoperatively. Ropivacaine 0.5% was titrated with the Dixon and Massey up-and-down method using a stepwise change of 5 ml in each consecutive patient. Combined blocks of the femoral, the lateral femoral cutaneous and the obturator nerve were prerequisite for a successful lumbar plexus block. PATIENTS Thirty patients scheduled for lower limb orthopaedic surgery completed the study. MAIN OUTCOME MEASURES The minimum effective anaesthetic volume of ropivacaine 0.5% (ED50) to achieve a successful Shamrock lumbar plexus block in 50% of the patients. Further analysis of the data was performed with a logistic regression model to calculate ED95 and to estimate the effective doses for a sensory lumbar plexus block not requiring a motor block of the femoral nerve. RESULTS The Dixon and Massay estimate of the ED50 was 20.4 [95% confidence interval (95% CI) 13.9 to 30.0] ml ropivacaine 0.5%. The logistic regression estimate of the ED95 was 36.0 (95% CI 19.7 to 52.2) ml ropivacaine 0.5%. For a sensory lumbar plexus block, the ED50 was 17.1 (95% CI 12.3 to 21.9) ml and the ED95 was 25.8 (95% CI 18.6 to 33.1) ml. CONCLUSION A volume of 20.4 ml ropivacaine 0.5% provided a successful Shamrock lumbar plexus block in 50% of the patients. A volume of 36.0 ml would be successful in 95% of the patients. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT01956617.