Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.

The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.

Steady-state kinetics and dynamics of morphine in cancer patients: is sedation related to the absorption rate of morphine?

Eighteen patients suffering from chronic pain due to cancer completed a balanced, double-blind, double-dummy, two period cross-over trial comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after administration of morphine given as controlled-release (CR) tablets (every 12 h) and immediate-release (IR) tablets (every 6 h). The same total daily dose of morphine was given in both study periods. Patients received both test formulations for 4 days and on the final day of each period, peripheral venous blood samples for analysis of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were obtained. Pain intensity, sedation, and continuous reaction time (CRT) were assessed. No significant differences could be demonstrated in AUC/dose, Cmin, Cmax or fluctuation index values between the two treatments (IR and CR tablets) for either morphine or its metabolites. Tmax for morphine and its metabolites occurred significantly later after administration of CR tablets than after administration of IR tablets. There were no significant differences between the IR and the CR formulation with respect to analgesia and side effects, and there was no difference in the patients' overall impression of the two treatments. More important, there was no difference between the Tmax and the time to peak sedation after administration of IR tablets (P = 0.63). However, due to the relatively small number of patients and the variability in the data, the statistical power of the test was only 0.074. The risk of a type II error is 0.926. These data demonstrate the PK and PD similarities and differences between CR and IR morphine. They suggest that there may be a relationship between Tmax (determined by absorption rate) and sedation, but further evaluation of this potential relationship is needed.

Trial of intravenous lidocaine on painful neuropathy in cancer patients.

In 10 cancer patients with cutaneous allodynia, intravenous lidocaine (5 mg/kg body weight) or 0.9% NaCl was given in a double blind, cross-over study to determine the analgesic effect. One patient had complete and one had partial pain relief with lidocaine infusion, whereas three patients experienced partial pain relief with placebo. Neither lidocaine nor placebo reduced pain intensity or consumption of analgesics significantly during the study period. Intravenous infusion of lidocaine cannot be recommended as routine pain treatment in cancer patients with cutaneous allodynia or pain, but further studies are needed to test the effect of lidocaine on different peripheral stimuli.

[Respiratory depression following medication change from tramadol to morphine]. / Respirationsdepression efter omstilling fra tramadol til depotmorphin.

Respiratory depression following change of medication from tramadol to morphine is described in two patients. Tramadol is metabolized by cytochromoxidase CYP2D6 to O-desmethyl-tramadol with opioid agonist activity. Of the western population 7% have a mutation of the gene responsible for CYP2D6, resulting in low enzyme activity. These persons will have little effect of tramadol. When tailoring analgesia, the lack of response to tramadol may be interpreted as a need for opioid dose increase. In such cases, excessive opioid doses may be prescribed resulting in opioid side effects.

[High-dose epidural opioid treatment of malignant pain]. / Højdosis epidural opioidbehandling af maligne smerter.

A retrospective investigation was undertaken of 48 cancer patients receiving long-term treatment with high dosages of epidural opioids. Prior to introduction of the epidural catheter, the patients were in stable oral opioid treatment (median dose: 300 mg morphine/24 hours, range 40-1,360). The effect of stable epidural opioid treatment (median dose: 90 mg morphine/24 hours, range 16-600) in the first catheter was assessed as good in 20, reasonable in 14 and poor in 13. The effect could not be assessed in one patient. Twenty-nine patients could be assessed on pure and stable epidural opioid treatment. The effect was good in 14, reasonable in seven and poor in eight. If the patients were subdivided according to the type of pain, 16 had somatic and/or visceral types of pain while 13 had neurogenic pain. Epidural opioid treatment of neurogenic pain was found to produce statistically significantly poorer results than in the case of somatic/visceral pain (p less than 0.05). At the time of assessment, no statistically significant difference was present in the epidural opioid dosage between the groups. The patients were subdivided into a low dosage group and a high dosage group. The low dosage group comprised patients who had received oral opioid treatment with less than 300 mg morphine/24 hours and the high dosage group comprised patients who received equal or greater than 300 mg morphine/24 hours. Epidural opioid treatment was found to provide statistically significantly better results in the low dosage group (p less than 0.05). In this group, a tendency to better relief of neurogenic pain was observed as compared with the high dosage group. At the time of assessment, no statistically significant difference was present in the epidural opioid dosage between the high dosage and low dosage groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Causes of pain and treatment effect in patients with cancer referred to a multidisciplinary pain clinic]. / Smerteårsager og behandlingseffekt hos cancerpatienter henvist til en tvaerfaglig smerteklinik.

The causes of pain were analysed in 200 patients referred to a multidisciplinary pain clinic for cancer patients. In 158 patients, pain caused directly by tumour growth was found, 116 patients had pain secondary to the cancer disease or treatment while 33 patients had pain caused by factors unrelated to the cancer disease. The patients had many different combinations of causes of pain and the majority had more than one cause of pain. At the first contact and after treatment for 1-2 weeks, the patients were asked whether they had pain on movement, at rest or pain which interrupted sleep. After treatment for 1-2 weeks and after treatment for more than two weeks, the patients assessed the relief of pain obtained (none, slight, moderate, considerable, complete). The majority of patients achieved relief of pain at rest and during sleep while movement was still accompanied by pain in a number of patients. The majority of patients considered that the relief of pain obtained was moderate or considerable. Treatment consisted of adjustment of medication, blockades and epidural opioids supplemented by psychological intervention and help from social workers in selected patients.

[Inhalation of levopromazine (Nozinan) in the treatment of status asthmaticus]. / Inhalation af levomepromazin (Nozinan) i behandling af status asthmaticus.

Levomepromazine reduces histamine-induced bronchial hyperresponsiveness in asthmatics without significant sedation. We present two patients with acute asthma refractory to conventional therapy, who were treated with inhalation of 2.5 mg levomepromazine. Until controlled studies have been done, we suggest that inhalation of levomepromazine be restricted to patients with asthma refractory to conventional therapy.

[Intravenous lidocaine in the treatment of chronic pain caused by bone metastases]. / Intravenøs lidokain i behandlingen af kroniske smerter forårsaget af knoglemetastaser.

A controlled double-blind investigation was undertaken in which ten patients with painful bone metastases were treated with intravenous lignocaine in a dosage of 5 mg/kg body-weight infused over a period of 30 minutes or the same volume of isotonic saline. None of the patients experienced prolonged pain relief but five patients experienced considerable pain relief immediately and/or one hour after the infusion of lignocaine.

[Treatment of cancer pain in Denmark. A questionnaire survey]. / Behandling af cancersmerter i Danmark. En spørgeskemaundersøgelse.

A questionnaire survey was carried out with the aim of evaluating knowledge about and practice of cancer pain treatment in Denmark. A questionnaire was sent to a 10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%) returned the questionnaires and after the exclusion of those doctors who never treated cancer patients, 577 (54%) were analyzed. Their knowledge of the principles and practice of cancer pain treatment was evaluated by means of 14 multiple-choice and open questions. Their ability to apply their knowledge in practice was evaluated by analyzing their suggested treatment of three simulated patient cases. Ninety-seven percent of the physicians recognized difficulties in cancer pain treatment, the most frequent being side effects of drugs and inadequate pain relief. It appeared from the proposals for pain treatment of the patient cases that the majority of the physicians could treat both pain from bone metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested coanalgesics for neuropathic pain (20%). Older physicians performed less satisfactorily than did their younger colleagues. Basic pain treatment skills have been acquired by the Danish physicians. However, in the future emphasis should be placed on the treatment of neuropathic pain with coanalgesics and the management of opioid side-effects.

The effect of sodium citrate on the pH and the amount of gastric contents before general anaesthesia.

Sixty patients were prospectively studied with respect to the volume and pH of their gastric contents after allocation to one of three preoperative treatments. All patients received diazepam (Apozepam) 5 mg the night before operation and 10 mg at 06.30 on the morning of operation. One group received sodium citrate solution 50 ml perorally at 06.30, 75-370 min before operation. A second group received water 50 ml perorally at 06.30, 100-405 min before operation. The third group received 50 ml water at 06.30 and 50 ml sodium citrate solution perorally just before admission to the operation theatre, 15-50 min before aspiration. Statistical analysis showed elevated pH and volume of gastric contents in the group receiving water in the morning and sodium citrate solution just before admission to the operating theatre immediately after induction of anaesthesia. There was no statistically significant difference of pH and aspirated volume between the group receiving water and the group receiving sodium citrate at 06.30.

Postural stability during long-term treatment of cancer patients with epidural opioids.

Ten cancer patients treated with stable doses of epidural opioids were tested for postural stability. The postural stability was measured using a quantitative Romberg's test, performed on a computerized force-plate system. Sway tendencies in the sagittal and the transverse directions were recorded. The postural stability of the patients was compared with values obtained from healthy controls. Comparing the cancer patients with the controls, postural stability in eight out of ten patients was intact. The study suggests that long-term epidural opioid treatment has little influence on the patient's ability to stand safely.

Continuous reaction time after single dose, long-term oral and epidural opioid administration.

Auditory continuous reaction time was studied in three treatment groups. Twenty opioid naive patients received intramuscular morphine 0.15 mg kg-1 bodyweight for premedication. Thirty-one cancer patients were treated with oral opioids, 180 mg morphine per 24 h (median). Twenty-two cancer patients were treated with epidural morphine, 79 mg morphine per 24 h (median). The treatment groups were compared to a control group of 44 healthy persons taking no analgesics. The reaction time was measured using 152 auditory signals and summarized as 10%, 50% and 90% percentiles. Analysing reaction time distributions, the opioid naive patients showed the greatest difference to the control group in the shortest reaction times while chronic opioid users showed the greatest difference for the longest reaction times. There seems to be a qualitative difference in reaction time distribution, between opioid naive individuals treated with single dose morphine and cancer patients in long-term treatment.

The protective effect of inhaled levomepromazine (Nozinan) on histamine-induced bronchial constriction.

The effect of inhaled levomepromazine (Nozinan, Veractil) on bronchial responsiveness to inhaled histamine was investigated in asthmatics. In a double blind, randomized controlled study, 12 asthmatics (FEV1% pred 52-96%, and PC20 histamine 1.01 mg/ml (geometric mean)) were challenged before and after inhalation of levomepromazine in three different doses. Before and after each inhalation of levomepromazine, PC20, FEV1, the continuous reaction time (CRT) and the subjective sedation score (VAS) were determined. A dose-dependent increase in PC20 was observed after inhalation of levomepromazine. PC20 was increased by up to 4.02 two-fold concentration differences (doubling), i.e. up to a 38-fold increase from the basic values. Inhalation of the two higher doses of levomepromazine had a small sedative effect evaluated from an increase in CRT and the VAS-score and corresponding to the plasma concentrations. We conclude that inhaled levomepromazine has a dose-dependent protective effect on histamine-induced bronchial hyperresponsiveness in asthmatics and that inhalation of levomepromazine was well tolerated. The mechanism by which levomepromazine acts on histamine-induced bronchial hyperresponsiveness is not known but it could be partly explained by the antihistaminic effect. In this respect levomepromazine bears comparison with the most potent second generation antihistamines. The plasma concentrations of levomepromazine measured corresponded to those seen after oral intake of 5-10 mg levomepromazine.

Comparison of oral controlled release morphine and epidural morphine in the management of postoperative pain.

Oral controlled release morphine (CRM) was compared in a double-blind study with epidural morphine (EM) for postoperative pain relief in 20 patients undergoing knee arthrotomy under epidural anesthesia. Ten patients received 30 mg CRM orally and saline epidurally (CRM group), and ten patients received placebo tablets orally and 4 mg morphine epidurally (EM group), both at the time of skin incision and then every 8 hr for 48 hr during which patients evaluated pain intensity using a visual analog scale. Nine of the ten patients in the EM group had good relief of pain throughout the study period. Seven of the ten patients in the CRM group needed rescue analgesics within 6 hr of the initiation of the study (P less than 0.01). We conclude that CRM is not suitable for the control of early postoperative pain, whereas epidural morphine is excellent.