Assessing the effectiveness of a hospital palliative care team.

A prospective study was carried out of 125 hospital inpatients with malignant disease, referred to the King's College Hospital advisory palliative care team. A palliative care assessment (PACA) tool was developed in order to assess the outcome of interventions made within two weeks of referral with regard to: symptom control, change in the patients' and their relatives' insight regarding diagnosis and prognosis, and facilitation of patient placement. Reliability was assessed by cross-observer analysis, and validity by comparison with data obtained using the McCorckle symptom distress scale in a separate group of hospice inpatients. At initial assessment, the commonest symptom was pain, as reported by 74% of patients. One-third of the patients were unsure of their diagnosis and placement had not been decided in 61%. In total, the team undertook 245 pharmacological interventions for symptom control, 165 interventions regarding insight and 114 interventions concerning placement. Analysis of the data showed statistically significant improvements in pain (p < 0.001), nausea (p < 0.009), insomnia (p < 0.004), anorexia (p < 0.001) and constipation (p < 0.02). Discussion regarding diagnosis significantly changed the insight of patients (p < 0.001) and relatives (p < 0.02). Appropriate placement was assisted by interventions undertaken by the team. This study shows that a hospital palliative care team is effective at improving symptom control, facilitates understanding of the diagnosis and prognosis, and contributes to the appropriate placement of patients.

Lumbar plexus block: an anatomical study.

The anatomy of the lumbar plexus and the various approaches used to perform lumbar plexus blockade are reviewed. A single needle technique for a posterior approach to the plexus at the L2-3 interspace is described. This technique was used bilaterally in six intact cadavers, and the extent of spread of an injected dye was documented photographically during a subsequent detailed dissection of the region. In all cases, dye was confined to the posterior part of the psoas muscle, and tracked down the nerves of the lumbar plexus. No dye was seen anterior to the psoas, around the sympathetic chain, on the sacral plexus or in the extradural or subarachnoid spaces. Further studies in patients with needle position and drug disposition being confirmed using computerised tomography and X ray scanning were in agreement with the results observed in the cadavers. This technique represents a simple approach to the lumbar plexus which does not require needle localisation by X ray screening.

Morphine-6-glucuronide disposition in renal impairment.

Twelve patients with chronic renal failure (dialysis-dependent) and six with good renal function after renal transplantation received i.v. morphine-6-glucuronide (M6G) 30 micrograms kg-1 as part of a standardized anaesthetic technique for minor surgery. Continuous peritoneal dialysis was commenced 6 h after M6G administration in six of the dialysis-dependent patients. Serum was sampled for up to 12 h and analysed for morphine and M6G by high pressure liquid chromatography. Morphine was not detected. Mean (SD) derived pharmacokinetic variables for the three groups (transplant, renally impaired non-dialysed and renally impaired dialysed, respectively) were: elimination half-life 2.14 (0.69) h, 27.10 (15.8) h, 17.33 (4.6) h; clearance 96.0 (34.9) ml min-1, 10.57 (5.57) ml min-1, 14.3 (6.2) ml min-1; volume of distribution 0.19 (0.03) litre kg-1, 0.25 (0.06) litre kg-1, 0.27 (0.06) litre kg-1. The elimination half-life was shorter (P < 0.01) and the clearance greater (P < 0.01) for the transplanted group compared with the dialysed and non-dialysed groups. Peritoneal dialysis for the second 6 h after drug administration had little effect on M6G disposition as assessed by comparison with data obtained from the non-dialysed group.

Audit of neural blockade for palliative care patients in an acute unit.

During the period from September 1990 to March 1992, 155 nerve blocks were performed for 125 patients as part of the clinical management of pain due to malignant disease. The efficacy, in terms of pain score reduction, and spontaneously reported side effects secondary to these procedures were prospectively audited. Neural blockade was undertaken in accordance with strict clinical criteria, and medication was optimized with the aim of achieving maximum analgesia with minimum side effects at all times. Pain was assessed before the block, 24 hours after the block and at follow-up (two to six weeks) using visual analogue scores or verbal rating scales. All patients were audited. The total (all patients, all blocks) median (lower-upper quartile) pain score dropped from 8 (6-10) cm before the block to 2 (0-4) cm at 24 hours after the block (p < 0.05) and to 1 (0-4) cm at follow-up (p < 0.005). A concomitant reduction in analgesic requirements was observed. The incidence of serious side effects was low (two patients in this series). The results indicate the usefulness of these techniques for patients in the palliative care setting.

Morphine-6-glucuronide: effects on ventilation in normal volunteers.

The respiratory responses to intravenous morphine sulphate (0.12 mg/kg), morphine-6-glucuronide (M6G: 0.03 mg/kg) and placebo were assessed in 6 healthy volunteers, using a single blind randomised crossover design. Five of these subjects underwent an additional study of M6G at 0.06 mg/kg. Respiratory rate, minute volume and end-tidal CO2 were continuously measured using a low resistance non-rebreathing circuit, a mass spectrometer and a dry gas meter. The ventilatory responses to CO2 exposures (5.5% for 4 min) were assessed 40 and 20 min before, and 20, 40 and 80 min after drug administration. Following placebo and M6G (at both doses) no change in end-tidal CO2 occurred whilst the subjects were breathing air, whereas following morphine a significant rise was seen (P less than 0.05). Morphine reduced the ventilatory response to 5.5% CO2 at all times tested (P less than 0.05) and M6G (at both doses) reduced the response to CO2 at 20 and 40 min after administration, but to a lesser degree than did morphine (P less than 0.05).

Disposition of morphine-6-glucuronide and morphine in healthy volunteers.

The pharmacokinetics and subjective side effects of i.v. morphine sulphate 120 micrograms kg-1 and morphine-6-glucuronide (M6G) 30 micrograms kg-1 were determined in six healthy volunteers, using a placebo-controlled, single-blind randomized crossover design. Five of these volunteers underwent an additional (non-randomized) study of M6G 60 micrograms kg-1. Subjective side effects were similar following both drugs, but of shorter duration following M6G. Morphine was not detected after administration of M6G. For M6G 30 micrograms kg-1 the mean (SD) volume of distribution, elimination half-life and clearance were 29.38 (18.36) litre, 2.05 (1.2) h and 187.81 (37.41) litre h-1, respectively. These values were not significantly different from those obtained for M6G 60 micrograms kg-1. In all subjects the volumes of distribution and clearances were significantly smaller for M6G than for morphine, but the elimination half-lives were similar.

Analgesic efficacy and CSF pharmacokinetics of intrathecal morphine-6-glucuronide: comparison with morphine.

The analgesic efficacy and CSF pharmacokinetics of intrathecal morphine sulphate and morphine-6-glucuronide (M6G) were compared in a single-blind crossover study. Lumbar intrathecal catheters were sited in three patients with chronic cancer pain, and morphine sulphate 500 micrograms or M6G 500 micrograms given via the catheter on separate days. CSF was sampled for 24 h following drug administration and analysed for morphine and M6G by high pressure liquid chromatography. The mean (SD) requirement for patient controlled analgesia with pethidine was 393.3 (227.4) mg/24 h during the morphine limb of the trial and 226.7 (113.6) mg/24 h during the M6G limb. M6G was not detected in CSF following administration of morphine. Fitting of CSF concentrations to triexponential curves revealed mean (SD) alpha, beta and gamma half-lives of 13.2 (7.4), 54.9 (31.5) and 222.5 (100) min for morphine and 11.2 (2.4), 67.3 (49.9) and 619.3 (629.7) min for M6G.

Ketanserin in reflex sympathetic dystrophy. A double-blind placebo controlled cross-over trial.

Ketanserin, a selective S2 serotonergic antagonist, was assessed against placebo in a double-blind cross-over study of 16 patients with chronic peripheral burning pain. Nine of these had signs of reflex sympathetic dystrophy (RSD). All patients underwent 4 intravenous regional treatments, 2 with ketanserin (10 mg for upper limb pain, 20 mg for lower limb pain) and 2 with placebo. In those patients with RSD ketanserin and not placebo provided significant (P less than 0.05) sustained pain relief as assessed by linear analogue scales. In patients who did not fulfil the criteria for RSD no significant relief was seen with placebo or ketanserin. Following tourniquet release, drowsiness, shakiness and faintness were reported at a higher (P less than 0.05) frequency after ketanserin than after placebo. All side effects were mild and transient, and no changes occurred in heart rate or blood pressure following ketanserin that were significantly different from those seen following placebo. A role for serotonin in the pathogenesis of RSD is proposed.

A double-blind comparison of epidural ketamine and diamorphine for postoperative analgesia.

Twenty patients who had abdominal hysterectomy under general anaesthesia were randomly assigned to receive either epidural ketamine (30 mg), or epidural diamorphine (5 mg) peri-operatively and on first request for analgesia. Failure to obtain satisfactory analgesia with one of the agents was treated by epidural administration of the other. Pain was assessed by an independent observer, and by the patient using a visual analogue scale. The mean (SD) pain score on recovery from general anaesthesia, on a scale of 0-4, was 2.9 (1.2) for the ketamine group and 1.0 (1.0) for the diamorphine group (p less than 0.01). The mean (SD) time to first request for analgesia was 272 (206) and 72 (41) minutes in the diamorphine and ketamine groups respectively (p less than 0.01). All patients in the diamorphine group obtained adequate analgesia, but all patients in the ketamine group were changed to epidural diamorphine. Epidural ketamine does not appear to be a sufficiently effective alternative to epidural diamorphine for routine use in postoperative pain.

The prolonged use of atracurium in a patient with tetanus.

A case of a patient with tetanus is reported in whom an atracurium infusion and artificial ventilation were needed in addition to sedation to control the muscle spasms. The atracurium infusion was used for 71 days, the longest time ever recorded, at a mean rate of 1.3 mg/kg/hour at the end of infusion. The plasma atracurium and laudanosine concentrations were 1.5 micrograms/ml and 0.985 micrograms/ml respectively. Subsequently there was an exponential decline in the serum laudanosine concentration which had decreased to 0.014 micrograms/ml 24 hours later. These results suggest that prolonged use of atracurium by infusion is not associated with excessive cumulation of laudanosine when renal and hepatic function are normal.