pain relief mediated by implantable drug delivery devices.

Various totally implantable drug delivery systems from single access ports to micropumps are now available for administration of repeated boluses, and continuous or programmable infusions. In this respect, emphasis is given to a relatively cheap, totally implantable system for self-administering intraspinal opiates in the treatment of cancer pain. The SECOR pump system, developed by Cordis, consists of a dual pump with refill port and safety valve. The volume of the pliable reservoir is 12 ml and refill is accomplished with a 25-G needle. The bolus delivered with each transcutaneous activation of the pumps is 0.1 ml. Clinical results demonstrated that this patient-controlled drug delivery system is safe and provides excellent pain relief associated with terminal cancer. A possible advantage of this drug delivery system over continuous infusion pumps is that patients can elect to have the morphine delivered only when they feel pain. Thus pain relief would be maximized and tolerance build-up would be minimized.

Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain.

Morphine is increasingly used in patients with chronic non-cancer pain, but a major concern associated with chronic use relates to possible cognitive side-effects. The aim of this long-term prospective study was to evaluate the cognitive impact of oral sustained release morphine in patients with non-cancer pain. A battery of neuropsychological tests to explore attention, psychomotor speed and memory was administered. The effects of morphine on pain, quality of life, mood, subjective memory impairment and side-effects were also investigated. Evaluations were performed at baseline in patients free from opioids and then after 3, 6 and 12 months. Twenty-eight patients were included: 18 received oral sustained morphine (range 40-140 mg/day), ten patients stopped morphine prematurely because of side-effects or insufficient pain relief and were followed as a control group. There was no impairment of any neuropsychological variable over time in the morphine treated patients in comparison with the control group. Two measures of information processing speed - the Stroop interference score and the digit symbol test were improved at 6 and 12 months and there were significant correlations with the pain relief and improvement of mood. Self-reported memory impairment improved notably in responders to morphine. Morphine induced persisting effects on pain, and to a lesser extent on quality of life and mood. The visual analog scale score for side-effects increased at 12 months and essentially consisted of gastrointestinal disorders. This study demonstrates that 12 months treatment with oral morphine does not disrupt cognitive functioning in patients with chronic non-cancer pain and instead results in moderate improvement of some aspects of cognitive functioning, as a consequence of the pain relief and concomitant improvement of well-being and mood.

Lysine acetyl salicylic acid in acute renal pain.

The effect of repeated doses of 1.8 g lysine acetyl salicylic acid (LAS) i.v. on severe pain secondary to acute renal colic (ARC) was studied in 45 consecutive patients. Clinically acceptable analgesia was obtained in 65% of the cases. No additional pain relief was achieved with the combination of pethidine 100 mg i.v. + metoclopramide 10 mg, i.m. (narcotics). pain relief occurred within five minutes in one third of the patients while in the rest within 30 minutes. Significant reduction of systolic blood pressure (mean +/- S.D.) 23.8 +/- 19.5, pulse rate (mean +/- S.D.) 19.5 +/- 10.1 and vomiting were noted in patients who had pain relief. The incidence of nausea has increased after LAS administration. No other side effects were observed. LAS might therefore be applied as a first-hand alternative to narcotics for the treatment of ARC.

Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics.

Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events--such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data, at least in acute pain models, indicates that more meaningful overviews or meta-analysis may be possible. This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data, and then used that relationship to derive dichotomous from continuous information in randomised controlled trials (RCTs) of analgesics. Individual patient information from 13 RCTs of parallel-group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) and the proportion of patients with greater than 50% pain relief (> 50%maxTOTPAR) for the different treatments. The relationship between the measures was investigated in 45 actual treatments and 10,000 treatments simulated using the underlying actual distribution; 1283 patients had 45 separate treatments. Mean %maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR (r2 = 0.90). The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50% pain relief in 42 of 45 treatments, and 98.8% of 10,000 simulated treatments. For seven effective treatments, actual numbers-needed-to-treat (NNT) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data.

Treatment of deafferentation pain by chronic stimulation of the motor cortex: report of a series of 20 cases.

Twenty patients with deafferentation pain were treated by chronic stimulation of the motor cortex. The central fissure was localized using stereotactic MRI and the motor cortex was mapped using intra-operative somatosensory evoked potentials. Seven patients with trigeminal neuropathic pain experienced definite pain relief varying between 40 and 100%. Ten patients had central pain secondary to central nervous system lesions. A satisfactory long-lasting pain control (pain relief > 40%) was obtained in five of them (50% of cases). One patient with pain from peripheral nerve injury obtained more than 80% pain relief. Two patients had pain from spinal cord lesions. One did not respond but the other obtained an excellent long-term result. The location of the effective stimulation plots was in agreement with the somatotopic maps of the primary motor cortex. One patient developed a small extradural haematoma which resolved spontaneously. None of the patients developed seizure activity. This study confirms the potential value of motor cortex stimulation in the treatment of certain forms of intractable pain, especially in cases with trigeminal neuropathic pain.

Epidural administration of midazolam with saline or bupivacaine for postoperative pain

Postoperative pain relief and sedation with epidural midazolam-saline or midazolam-bupivacaine were studied in 46 patients after elective upper abdominal surgery. They were divided into 6 groups. In each group, 10 ml saline, 10 ml saline+midazolam 0.05 mg.kg-1, 10 ml saline+midazolam 0.1 mg.kg-1 (saline group), 0.25% bupivacaine 6 ml, 0.25% bupivacaine 6 ml + midazolam 0.05 mg.kg-1 or 0.25% bupivacaine 6 ml + midazolam 0.1 mg.kg-1 (bupivacaine group) was administered via epidural catheter for complaint of pain. For 120 minutes after epidural injection, blood pressure (BP), heart rate (HR), respiratory rate (RR), sedation score, and serum concentration of midazolam (conc midazolam) were evaluated. The time interval until next complaint of pain (pain relief time) was measured. In midazolam injected group, BP, HR, RR were not changed from preinjection value, but sufficient sedation was obtained and pain relief time was significantly prolonged compared with saline or bupivacaine injected group. Midazolam level was lower than that of sedation level. There were no significant differences between saline group and bupivacaine group, but the pain relief effect was slightly stronger in bupivacaine group. It is concluded that epidural saline - midazolam or 0.25% bupivacaine - midazolam is useful for postoperative pain relief after upper abdominal surgery.

Studies on the effectiveness of obstetric epidural analgesia. I. Vaginal delivery (author's transl)

In a retrospective study 1,000 women who in 1979 had undergone a delivery either under epidural-anaesthesia or without, and instead either relation training or pethidine in small doses (20-30 mg i.v.) at the Ulm Department of Obstetrics, were followed up by questionnaire. The women of the epidural group felt that they had been adequately informed about the various possibilities of pain relief during labour, while some of the control group felt that they had been inadequately or even incorrectly informed. In the epidural group, pain relief during labour was such that 90% had hardly experienced any, or only mild discomfort, similar degree of pain relief was described by a many as 68.7% of the control group. Especially in the case of primigravida, the women of the epidural group had an insufficient urge to bear down, hence the rate of forceps delivery was relatively high, whereas this problem did not arise in the control group, where the forceps rate was markedly lower. The incidence of headache and back pain was only slightly higher in the epidural as compared to the control group, where other complaints were more frequent. 82% of the epidural group said that they would again choose this form of analgesia for future deliveries, 15% would not. In the control group 22% said that they would like an epidural for future deliveries, while 21% would not. The Apgar scoring and pH values of the newborn showed no significant differences between the groups.

The nature and management of labor pain: part II. Pharmacologic pain relief.

A group of family physicians, obstetricians, midwives, obstetric anesthesiologists, and childbirth educators attended an evidence-based symposium in 2001 on the nature and management of labor pain and discussed a series of systematic reviews that focused on methods of labor pain management. Parenteral opioids provide modest pain relief in labor, and little evidence supports the use of one agent over another. Epidural analgesia is used during labor in most large U.S. hospitals, and its use is rapidly increasing in small hospitals. Although epidural analgesia is the most effective form of pain relief, its use is associated with a longer labor, an increased incidence of maternal fever, and increased rates of operative vaginal delivery. The effect of epidural analgesia on rates of cesarean delivery is controversial. Nitrous oxide provides a modest analgesic effect, but it is used less often in the United States than in other developed nations. Paracervical block provides effective analgesia in the first stage of labor, but its use is limited by postblock bradycardia. Research is needed regarding which pain-relief options women would choose if they were offered a range of choices beyond epidural analgesia or parenteral opioids.

The natural history of pain in alcoholic chronic pancreatitis.

BACKGROUND & AIMS: The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS: A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS: Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS: In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.

Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan.

Postoperative pain relief with codeine was evaluated in 11 women undergoing hysterectomy. Patient-controlled analgesia (PCA) was used to administer codeine. After the study the patients were phenotyped with respect to the O-demethylation of dextromethorphan (cytochrome P4502D6 polymorphism). Ten were extensive metabolisers and one a poor metaboliser. There was a nine-fold variation in the minimum plasma concentration of codeine consistent with pain relief (40-350 ng ml-1). Two patients did not experience any effect of codeine, one of whom was a poor metaboliser of dextromethorphan, confirmed by genotyping. In the other nine patients the effective dose of codeine varied from 4.8-25.3 mg h-1.