The effect of dextromethorphan, alone or in combination with ibuprofen, on postoperative pain after minor gynaecological surgery.

BACKGROUND: Experimental studies have demonstrated that peripheral tissue injury may lead to hyperexcitability of nociceptive neurones in the dorsal horn, in part mediated by N-methyl-D-aspartate (NMDA)-receptor mechanisms. Sensitisation of dorsal horn neurones may be an important contributor to postoperative pain. The aim of the present study was to investigate the effect of the NMDA-receptor antagonist dextromethorphan on pain after minor gynaecological surgery, and to evaluate a potential additive effect with ibuprofen. METHODS: In a double-blind, placebo-controlled study, 100 patients scheduled for elective termination of pregnancy were randomised to receive placebo, oral ibuprofen 400 mg, oral dextromethorphan 120 mg, or a combination of ibuprofen 400 mg and dextromethorphan 120 mg, 1 h before surgery. Pain and analgesic requirements were assessed 0.5, 1 and 2 h after operation. RESULTS: We observed no effect of dextromethorphan on visual analogue scale (VAS) pain scores or analgesic consumption, and no additive or synergistic analgesic effects between ibuprofen and dextromethorphan. Ibuprofen reduced pain scores compared with placebo, and analgesic consumption compared with both placebo and dextromethorphan. The combination of ibuprofen and dextromethorphan increased preoperative nausea compared with both placebo and ibuprofen, whereas no statistically significant side effects were observed with dextromethorphan alone. CONCLUSION: No analgesic effects of oral dextromethorphan 120 mg on pain after surgical termination of labour, and no additive analgesic effects when combined with ibuprofen 400 mg, were observed. Ibuprofen reduced both VAS pain scores and analgesic consumption compared with placebo.

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy.

Dextromethorphan is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that NMDA-receptor antagonists may potentiate the effect of analgesics such as morphine, local anesthetics and NSAIDs. Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting, possibly related to administration of insufficient doses of the drug. Fifty patients scheduled for non-malignant elective abdominal hysterectomy in general anesthesia were randomized to receive oral dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received patient-controlled analgesia with morphine for 24 h postoperatively as the only analgesic. Patient-controlled analgesia (PCA) morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during cough, or during mobilization, pressure pain detection thresholds, von Frey hair pain detection thresholds, or peak flow. At 24 h after operation, hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption (Rs=0.28, P=0.05). Three months postoperatively, hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (nausea, vomiting, sedation). In conclusion, oral dextromethorphan 150 mg reduced PCA morphine consumption immediately (0-4 h) after hysterectomy, without prolonged effects on pain or wound hyperalgesia. A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA morphine consumption was demonstrated.

Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery.

We studied 60 patients undergoing operation on the kidney with combined general and epidural anaesthesia, in a double-blind, randomized, controlled study. Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after operation, or placebo. During the first 24 h after surgery, all patients received 4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation, patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg. In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg, lockout time 15 min) was offered from 0 to 48 h after operation. Patients who received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h after operation, compared with patients who received placebo (P = 0.002 and P = 0.127, respectively). There were no significant differences in pain (VAS) at rest, during mobilization or cough, PCA morphine consumption, sensory block to pinprick, pressure pain detection threshold assessed with an algometer, touch and pain detection thresholds assessed with von Frey hairs, peak flow or side effects other than sedation. The power of detecting a reduction in VAS scores of 20 mm in our study was 80% at the 5% significance level. We conclude that we were unable to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery.

Effect of systemic N-methyl-D-aspartate receptor antagonist (dextromethorphan) on primary and secondary hyperalgesia in humans.

Dextromethorphan is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and central hyperexcitability of dorsal horn neurones. We studied 24 healthy, unmedicated male volunteers, aged 21-28 yr, in a randomized, double-blind, placebo-controlled, crossover study. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On three separate days, at least 1 week apart, subjects were given oral dextromethorphan 60 mg, 120 mg or placebo. Dextromethorphan reduced the magnitude of secondary hyperalgesia to pinprick but not to stroke. Dextromethorphan had no influence on primary hyperalgesia, pain during prolonged noxious heat stimulation or heat pain detection thresholds in undamaged skin. Side effects were frequent but clinically acceptable. The effects of dextromethorphan were in agreement with experimental studies indicating that dextromethorphan is a NMDA receptor antagonist. The effects of dextromethorphan in the burn injury model were similar to those of ketamine and distinct from those of local anaesthetics and opioids.

Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans.

Ketamine reduces nociception by binding noncompetitively to the N-methyl-D-aspartate (NMDA) receptor, activation of which increases spinal hypersensitivity. We studied 19 healthy, unmedicated male volunteers, aged 20-31 yr. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectangular thermode. On 3 separate days, at least 1 week apart, subjects received a bolus of either ketamine 0.15 mg kg-1, ketamine 0.30 mg kg-1 or placebo, delivered by a mechanical infusion pump over 15 min. The bolus was followed by continuous infusion of ketamine 0.15 mg kg-1 h-1, ketamine 0.30 mg kg-1 h-1 or placebo, respectively, for 135 min. Ketamine reduced the magnitude of both primary and secondary hyperalgesia, and also pain evoked by prolonged noxious heat stimulation, in a dose-dependent manner. In contrast, ketamine did not alter phasic heat pain perception (perception of transient, painful, thermal stimuli) in undamaged skin. The analgesic effects of ketamine in the burn injury model are in agreement with results from experimental studies, and can be distinguished from those of local anaesthetics and opioids. Side effects caused by continuous infusion of ketamine 0.15 and 0.30 mg kg-1 h-1 were frequent but clinically acceptable.

Variation in spinal analgesia with plain bupivacaine 0.5% when repeated in the same patient.

The study was done to see if it was possible to predict the level of analgesia in repeated spinal blocks with our routine technique where the patient is seated during injection of plain 0.5% bupivacaine 3.5 ml at the L3-L4 interspace and placed in the lithotomy position after 0.5 min. Thirty patients with tumour of the bladder had two spinal blocks during a 13-month period. The segmental spread of sensory loss was tested with the pin-prick technique. A wide range of height of blocks was found, increasing with age. Regression analysis on maximum cephalad spread of the second spinal analgesia against the first had a slope of 0.48 (P less than 0.01 for the hypothesis that the slope is zero). A significant correlation between the time for maximal cephalad spread was found, while the correlation between duration of thoracal analgesia was non-significant.

[Inguinal paravascular block (3-in-1 block)]. / Den ingvinale paravaskulaere blokade ("3-i-1" blok).

The three main nerves from the lumbar plexus may be blocked by injection of local anesthetic into the facial envelope of the femoral nerve ("three-in-one block"). The femoral nerve may be localized by obtaining paresthesia, by employing a nerve stimulator or by the loss of resistance technique. We prefer the use of a nerve stimulator. The "three-in-one block" may be employed for immediately pain relief of pain and for treatment of postoperative pain from fractures in the hip, femur and knee. Introduction of a catheter into the femoral nerve sheath is recommended to provide continuous block of the lumbar plexus for relief of postoperative pain.

Spinal analgesia with plain 0.5% bupivacaine administered at spinal interspace L2-3 or L4-5.

Forty patients (age range 60-79 yr) undergoing transurethral surgery were allocated randomly to receive 0.5% plain bupivacaine 4 ml at the L2-3 (n = 20) or L4-5 (n = 20) space. The solution was injected over 30 s with the patient in the sitting position. The patient was kept sitting for 2 min, then placed supine and, 5 min later, placed in the lithotomy position. No significant differences were found in onset time, extent and duration of analgesia or duration of motor block.

Plain bupivacaine: 0.5% or 0.25% for spinal analgesia?

Plain 0.5% bupivacaine 3 ml was compared with plain 0.25% bupivacaine 6 ml for spinal anaesthesia during transurethral surgery in 40 patients. The solutions were injected over 30 s at the L3/4 space with the patient in the sitting position. The patient was kept sitting for 2 min, supine for 5 min and then placed in the lithotomy position. No significant differences were found in onset time, extent of cephalad spread, duration of sensory or motor blockade, or side effects. The use of a 0.5% plain solution of bupivacaine did not appear to confer any advantage over the 0.25% solution.

Respiratory depression following postoperative analgesia with epidural morphine.

Eighteen healthy patients subjected to operation for duodenal ulcer were allocated randomly to one of two regimes of analgesic treatment with epidural morphine. The analgesic regime was started either per- or postoperatively. Epidural morphine in doses of 4 mg was given until satisfactory pain relief was achieved. PaCO2 and respiratory rate were measured hourly for 10 h and a nearly identical respiratory depression was found in the two groups. Peak PaCO2-values were seen in the 5th and 6th postoperative hour. The respiratory rate was initially high and declined during the first postoperative hours. Only one patient in each group had a pathologically low respiratory rate (8 min-1), but this was transient and seen in the 10th postoperative hour. The needs for epidural morphine on the first postoperative day were highest in the peroperative group. It is concluded that a peroperative start of pain treatment with epidural morphine does not affect the degree of respiratory depression or reduce the postoperative analgesic requirements.

Urinary retention during i.m. and extradural morphine analgesia.

In the postoperative period fifty-six healthy patients undergoing cholecystectomy or operations for duodenal ulcer, received, in a randomized order, i.m., "high-level" or "low-level" extradural morphine. Thirty-five per cent in the i.m. group, 33% in the high-level group and 50% in the low-level group suffered urinary retention, in all cases within the first 24 h. The mean cumulative dose of morphine necessary for pain relief was in the same range (13.4-16.5 mg) during the first 2 h of therapy for all groups, while the amounts after 24 and 48 h were twice to four times with the i.m. route compared with the extradural route. A peripheral effect of morphine on the urinary bladder is possible and the mechanism of action is discussed.

Preoperative starvation and blood glucose concentrations in children undergoing inpatient and outpatient anaesthesia.

Blood glucose concentrations were measured in 82 children undergoing inpatient anaesthesia and in 46 children undergoing anaesthesia as outpatients. The children were aged between 6 months and 9 yr. Outpatients were fasted from bedtime, while inpatients were randomly allocated to two groups. In group A the children were fasted from bedtime, whereas in group B the children were fed 6 h before anaesthesia. There was no difference in mean blood glucose concentration between the fasted inpatients and outpatients nor between children younger than, or older than, 4 years of age. A blood glucose concentration of less than 40 mg dl-1 was found in only one of the fasted children (1%). The mean blood glucose concentration was greater in group B than A, but only significantly so for children older than 4 yr. It is concluded that to minimize the risks of hypoglycaemia and inhalation of vomit on induction of anaesthesia children older than 6 months should be fasted overnight and operated on in the morning.

Postoperative analgesia and lung function: a comparison of intramuscular with epidural morphine.

Thirty healthy patients subjected to cholecystectomy or operation for duodenal ulcer were allocated randomly for postoperative analgesic treatment with morphine i.m. or epidurally. Morphine was given only at the request of the patients and only as much was given as was needed to obtain satisfactory pain relief. Patients in the epidural group were given morphine exclusively by epidural injection. In the epidural group a lower incidence of radiological changes in the lungs was found postoperatively - 21% as against 67%. Compared with the i.m. group, there was a higher arterial oxygen tension and a slower increase in alveolar-arterial oxygen difference. It is concluded that epidural morphine analgesia reduces the degree of postoperative lung dysfunction compared with conventional i.m. morphine treatment.