In this study, we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five patients scheduled for elective TKA under general anesthesia were randomly divided into three groups. Postoperative analgesia was provided with i.v. patient-controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in Group B, and epidural analgesia in Group C. Immediately after surgery, the three groups started identical physical therapy regimens. Pain scores, supplemental analgesia, side effects, degree of maximal knee flexion, day of first walk, and duration of hospital stay were recorded. Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups. Compared with Groups A and C, a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay were noted in Groups B and C. However, these benefits did not affect outcome at 3 mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than i.v. PCA with morphine. Because it induces fewer side effects, continuous 3-in-1 block should be considered the technique of choice. Implications: In this study, we determined that, after total knee arthroplasty, loco-regional analgesic techniques (epidural analgesia or continuous 3-in-1 block) provide better pain relief and faster postoperative knee rehabilitation than i.v. patient-controlled analgesia with morphine. Because it causes fewer side effects than epidural analgesia, continuous 3-in-1 block is the technique of choice.

Effects of Intravenous Patient-Controlled Analgesia with Morphine, Continuous Epidural Analgesia, and Continuous Three-in-One Block on Postoperative Pain and Knee Rehabilitation After Unilateral Total Knee Arthroplasty

Urinary retention is common after anesthesia and surgery, reported incidence of between 5% and 70%. Comorbidities, type of surgery, and type of anesthesia influence the development of postoperative urinary retention (POUR). The authors review the overall incidence and mechanisms of POUR associated with surgery, anesthesia and analgesia. Ultrasound has been shown to provide an accurate assessment of urinary bladder volume and a guide to the management of POUR. Recommendations for urinary catheterization in the perioperative setting vary widely, influenced by many factors, including surgical factors, type of anesthesia, comorbidities, local policies, and personal preferences. Inappropriate management of POUR may be responsible for bladder overdistension, urinary tract infection, and catheter-related complications. An evidence-based approach to prevention and management of POUR during the perioperative period is proposed.

Postoperative urinary retention: anesthetic and perioperative considerations.

Patients with impaired renal function may experience severe and prolonged respiratory depression when treated with morphine. This has been attributed to accumulation of the drug during renal failure. Three patients are described who had classical signs of intoxication with morphine in the absence of measurable quantities of morphine in the plasma. The observed clinical effect is attributed to accumulation of the pharmacologically active metabolite morphine-6-glucuronide, which is usually renally excreted. It is concluded that morphine does not accumulate in patients with renal failure but that accumulation of metabolites does occur. The previously reported observations of morphine accumulation during renal failure probably result from the use of radioimmunoassays that cannot distinguish between morphine and morphine-6-glucuronide. Thus the apparent morphine concentration measured with these assays in fact reflects the total quantity of morphine and morphine-6-glucuronide present.

https://www.bmj.com/content/bmj/292/6535/1548.full.pdf

Morphine intoxication in renal failure: the role of morphine-6-glucuronide.

Ockelbo disease: epidemic arthritis-exanthema syndrome in sweden caused by sindbis-virus like agent

Fentanyl, unlike morphine, is highly lipophilic and rapidly diffuses out of the epidural space. Respiratory depression is, therefore, unlikely when fentanyl is given epidurally. However, much of fentanyl's analgesic effect is mediated by systemic rather than spinal receptor binding. To test this hypothesis, we performed a prospective, double-blind, cross-over study comparing epidural and intravenous (IV) administration of fentanyl in 16 patients for the first 12 h after lower abdominal or lower extremity surgery. To allow direct comparison of these two routes of administration, patient-controlled analgesia was used so patients could self-titrate their analgesia. Patients were randomized to receive fentanyl initially by an epidural (group A, n = 8) or IV (group B, n = 8) catheter for 6 h, after which they were crossed-over to the alternate route by means of a hidden three-way stopcock. The degree of analgesia was subjectively evaluated by a visual analogue scale, and by an observer rating patient's comfort and sedation. Cumulative dosage of fentanyl was recorded, and plasma fentanyl concentrations were measured. The onset of analgesia and increase in plasma fentanyl concentrations were more rapid with intravenous fentanyl. However, after 60 min, analgesia (visual analogue scale 2-4 cm) or plasma fentanyl concentrations (0.3-0.7 ng/mL) did not differ between the two routes of administration. There were also no significant differences in the cumulative dosage of fentanyl within each group (epidural vs IV) or between the groups. Thus, the analgesic effects of epidural fentanyl appear largely mediated by systemic absorption. Intravenous fentanyl achieves a similar degree of analgesia and a more rapid onset of effect without the need for epidural catheterization.

Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration.

SUMMARY In a controlled clinical study of 20 patients undergoing arthrotomy a single dose of morphine 0.05 mg kg-1 administered extradurally resulted in more pronounced and prolonged pain relief than morphine 0.1 mg kg-1 i.m. in the period immediately after operation. This difference was significant between 2 and 11 h after morphine administration. The maximum analgesic effect for nine patients in the extradural group was obtained about 2 h after injection. Two of 10 in the extradural group experienced urinary retention. Other side-effects were mild for both groups. Plasma concentrations of morphine were measured in five patients in each group. Four hours after administration, morphine was not detectable in plasma in any of the extradural group and in two of the i.m. group. Our study gives further support for the theory that extradural morphine acts on the spinal cord.

Extradural and parenteral morphine: kinetics and effects in postoperative pain. a controlled clinical study

Forty patients undergoing arthroscopy were given an epidural dose of 0.05 mg morphine-HCl in 0.1 ml saline/kg body weight to study the disposition of morphine in the cerebrospinal fluid (CSF). In each patient one to three CSF samples were collected (86 samples in total). A mean peak concentration of 13 890 nmol/l was achieved 75 min after morphine administration. The compiled data show an elimination half-life of 162 min (r = 0.98). Individual half-lives in seven patients with three samples ranged from 61-172 min. Large interindividual variations were found in CSF-concentrations of morphine, 9- and 8-fold at 3 and 8 h, respectively, after the dose. However, 16 h after administration no patient had a concentration less than 81 nmol/l. At 8 h after the dose, CSF concentrations of morphine were significantly higher (P less than 0.05) in a group of patients (n = 5) kept uptilted (80 degrees), as compared to those in the supine position (n = 5). Such a difference was not observed 3 h after the dose. The sampling procedure and age also seemed to influence CSF concentrations of morphine. There was no correlation between the dose given in mg and the CSF concentrations achieved. Strict standardization is thus mandatory when studying the disposition of opiates in CSF after epidural or intrathecal administration. Since our calculated half-lives of morphine in CSF were similar to those reported in plasma, the long-lasting effect is probably related to the high initial morphine concentrations in CSF.

Kinetics of Morphine in Cerebrospinal Fluid After Epidural Administration

The pain-relieving effect of a single extradural dose of pethidine 25mg with and without adrenaline waS studied in 20 healthy women during labour. The study was open regarding the effects of pethidine but double-blind regarding the addition of adrenaline. In 14 of 19 women good or excellent analgesia was achieved for a period of 50–160 min. Pethidine with adrenaline 25 μg was not more effecnve than pethidine alone Eight of the 14 women showed signs of regional analgesia to pin-prick and temperature discrimination The patients had small (45-188 ng ml−1) concentrations of pethidine in plasma In eight patients the plasma concentrations of pethidine were maintained for at least 1.5 h. Extradural pethidine thus induces analgesia of short and variable duration. Repeated doses may be needed, resulting in accumulation of the drug in plasma with the risk of respiratory depression in mother or child.

Extradural pethidine with and without adrenaline during labour: wide variation in effect.

Extradural Pethidine With and Without Adrenaline During Labour: Wide Variation in Effect

Low intrathecal doses of opiates produce dose-dependent long-lasting elevation of the pain threshold in rats. The effect is postulated to be mediated by a direct action on the substantia gelatinosa of the spinal cord. Eight uncontrolled and two controlled studies in man showed a long duration of analgesia for most patients in the postoperative period. The duration of effect differs widely within and between studies. Using a double-blind design, we compared the relative efficacy of epidural and parenteral pethidine to control postoperative pain after total hip replacement. Preliminary pharmacokinetic data from six patients show that epidural doses of 20 or 60 mg pethidine give a similar pattern of absorption and elimination in plasma as 1 mg pethidine/kg body weight intramuscularly. The terminal elimination half-lives of pethidine in plasma are 5–7 h for all routes of administration. The possibility cannot be excluded that the analgesic effect of epidural pethidine is partly systemically mediated.

M. Garle

Papers

Extradural and parenteral morphine: kinetics and effects in postoperative pain. a controlled clinical study

Kinetics of Morphine in Cerebrospinal Fluid After Epidural Administration

Extradural pethidine with and without adrenaline during labour: wide variation in effect.

Extradural Pethidine With and Without Adrenaline During Labour: Wide Variation in Effect

Regional epidural analgesia: kinetics of pethidine.