Pharma clinics. How I treat...or preventing pain with "patches"]

There exists two distinct types of patches aiming at increasing the pain threshold either systematically or locally. The first type of analgesic patch is a real transdermal delivery system releasing fentanyl. Such potent opioid drug exerts a systemic effect. The other type of patch associates lidocain and prilocain to induce a local anesthesia of the skin without inducing a systemic effect.     

Prenatal detection of congenital idiopathic cataracts

We present a case of fentanyl overdose via mucous membrane absorption. A 31-year-old man presented to the emergency department in respiratory arrest. At intubation, a Duragesic transdermal patch (75 micrograms/h) was recovered from the buccal cavity. A second fentanyl transdermal patch (75 micrograms/h) was noted on the right lateral aspect of the thigh. Postmortem blood evaluation returned a venous fentanyl level of 17.2 micrograms/L. The therapeutic range for analgesic use is 1 microgram/L to 3 micrograms/L. Drug screens were positive for benzodiazepines and cocaine. Mass spectrophotometry/gas chromatography was used to determine fentanyl levels and to confirm drug screen results. Case history, findings at intubation, and high fentanyl blood concentration suggest the cause of respiratory arrest and death was fentanyl overdose.     

Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management

Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with strong analgesic activity. The analgesic efficacy of ketorolac has been extensively evaluated in the postoperative setting, in both hospital inpatients and outpatients, and in patients with various other acute pain states. After major abdominal, orthopaedic or gynaecological surgery or ambulatory laparoscopic or gynaecological procedures, ketorolac provides relief from mild to severe pain in the majority of patients and has similar analgesic efficacy to that of standard dosages of morphine and pethidine (meperidine) as well as less frequently used opioids and other NSAIDs. The analgesic effect of ketorolac may be slightly delayed but often persists for longer than that of opioids. Combined therapy with ketorolac and an opioid results in a 25 to 50% reduction in opioid requirements, and in some patients this is accompanied by a concomitant decrease in opioid-induced adverse events, more rapid return to normal gastrointestinal function and shorter stay in hospital. In children undergoing myringotomy, hernia repair, tonsillectomy, or other surgery associated with mild to moderate pain, ketorolac provides comparable analgesia to morphine, pethidine or paracetamol (acetaminophen). In the emergency department, ketorolac attenuates moderate to severe pain in patients with renal colic, migraine headache, musculoskeletal pain or sickle cell crisis and is usually as effective as frequently used opioids, such as morphine and pethidine, and other NSAIDs and analgesics. Subcutaneous administration of ketorolac reduces pain in patients with cancer and seems particularly beneficial in pain resulting from bone metastases. The acquisition cost of ketorolac is greater than that of morphine or pethidine; however, in a small number of studies, the higher cost of ketorolac was offset when treatment with ketorolac resulted in a reduced hospital stay compared with alternative opioid therapy. The tolerability profile of ketorolac parallels that of other NSAIDs; most clinically important adverse events affect the gastrointestinal tract and/or renal or haematological function. The incidence of serious or fatal adverse events reported with ketorolac has decreased since revision of dosage guidelines. Results from a large retrospective postmarketing surveillance study in more than 20,000 patients demonstrated that the overall risk of gastrointestinal or operative site bleeding related to parenteral ketorolac therapy was only slightly higher than with opioids. However, the risk increased markedly when high dosages were used for more than 5 days, especially in the elderly. Acute renal failure may occur after treatment with ketorolac but is usually reversible on drug discontinuation. In common with other NSAIDs, ketorolac has also been implicated in allergic or hypersensitivity reactions. In summary, ketorolac is a strong analgesic with a tolerability profile which resembles that of other NSAIDs. When used in accordance with current dosage guidelines, this drug provides a useful alternative, or adjuvant, to opioids in patients with moderate to severe pain.     

The effect of supervision of residents on quality of care in five university-affiliated emergency departments

BACKGROUND: The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios. METHODS: One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 micrograms/ml or bupivacaine 0.24% with fentanyl 4 micrograms/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0-10) with a minimum of adverse effects. RESULTS: There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts--bupivacaine 10.8-11 mg/h and fentanyl 18-18.4 micrograms/h--were given in both groups throughout the study. CONCLUSIONS: Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studies concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.     

Electronic measurements of relative tongue-palate contact time. Development and testing for orthodontic functional analysis

Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years; range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative care centers into a randomized, open, two-period, crossover study comparing transdermal fentanyl with sustained-release oral morphine. Patients received one treatment for 15 days followed immediately by the other for 15 days. Daily diaries were completed. Both treatments appeared equally effective in terms of pain control, as assessed by the Memorial Pain Assessment Card and European Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl was associated with significantly less constipation (p < 0.001) and less daytime drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter sleep duration (p = 0.008) than morphine. The World Health Organization (WHO) performance status and EORTC global quality of life scores showed no significant difference between treatment groups. Of those patients who were able to express a preference (n = 136), significantly more preferred the fentanyl patches (p = 0.037). We conclude that, in this study, transdermal fentanyl provided pain relief that was acceptable to cancer patients and was associated with less constipation and sedation than morphine. These reduced side effects may contribute to patients preference for the patches.     

Antitumor effect of positively charged resin in the hamster cheek pouch model

This paper presents the results of a detailed study of the pain epidemiology and health related quality of life (HRQL) in 150 chronic non-malignant pain patients consecutively referred to a Danish multidisciplinary pain center. Mean pain severity was 71.6 (SD = 18.5) on the VAS scale. Forty-two percent reported poor quality of sleep. HRQL was evaluated with the Medical Outcome Study-Short Form (SF-36), the Hospital Anxiety and Depression scale (HAD) and the Psychological General Well-Being Scale (PGWB). Compared with the normal population (NP) both SF-36 scores and PGWB scores were significantly reduced (P < 0.001) indicating that physical, psychological and social well-being were severely reduced. On the HAD scale 58% were found to have a depressive or anxiety disorder. Statistically significant but modest correlations were found between pain severity and HRQL. Psychological and social well-being was closely correlated. Sixty-three percent of the referred patients had neurogenic pain conditions. Of these, only 25% were treated with antidepressants or anticonvulsants at referral. Seventy-three percent were treated with opioids at referral. Mean opioid consumption was 64 mg of morphine per day (range 1-280 mg). Compared with the NP the chronic pain patients had used the health care system five times more often in the years prior to referral (P < 0.001). The study confirms the severe multidimensional impact of chronic pain and demonstrates that HRQL of chronic non-malignant pain patients is among the lowest observed for any medical condition.     

Analgesic potency of mu and kappa opioids after systemic administration in amphibians

The relative analgesic potency of 11 opioid agents was assessed by using the acetic acid test in amphibians. Systemic administration of the mu agonists, fentanyl, levorphanol, methadone, morphine, meperidine and codeine; the partial mu agonist, buprenorphine; and the kappa agonists nalorphine, bremazocine, U50488 and CI-977 was made by s.c. injection into the dorsal lymph sac of the Northern grass frog, Rana pipiens. All agents produced a dose-dependent and long-lasting analgesia which persisted for at least 4 hr. The analgesic effects of single doses of each agent were significantly blocked or reduced by pretreatment with naltrexone. Systemic opioids produced log dose-response curves which yielded ED50 values ranging from 1.4 nmol/g for fentanyl to 320.9 nmol/g for nalorphine. Comparison of ED50 values gave a rank order of analgesic potency = fentanyl > CI-977 > levorphanol > U50488 > methadone > bremazocine > morphine > buprenorphine > meperidine > codeine > nalorphine. The relative analgesic potency of mu opioids in amphibians was significantly correlated with relative analgesic potency of these same agents obtained on the mouse writhing and hot plate tests. These data suggest that the amphibian model may serve as an adjunct or alternative model for the testing of opioid agents. Furthermore, given the inactivity of kappa opioids on rodent hot plate and tail-flick tests, the acetic acid test in amphibians may be especially well-suited for the assessment of opioid analgesia after administration of kappa-selective opioids.     

Postoperative patient-controlled epidural analgesia with opioid bupivacaine mixtures

PURPOSE: To determine the efficacy and safety of patient-controlled epidural analgesia of morphine or fentanyl in combination with bupivacaine for postoperative pain relief. METHODS: Forty ASA I-II patients scheduled for major abdominal surgery were studied. After insertion of a lumbar epidural catheter, patients were given a non-opioid general anaesthetic. After surgery patients complaining of pain, received a loading dose of 2 mg morphine (Group I) or 50 micrograms fentanyl (Group II). For continuing pain, 1 mg morphine in 4 ml bupivacaine 0.125% (0.25 mg.ml-1 morphine and 1 mg.ml-1 bupivacaine, Group I) or 20 micrograms fentanyl in 4 ml bupivacaine 0.125% (5 micrograms.ml-1 fentanyl and 1 mg.ml-1 bupivacaine Group II) were administered. Blood pressure, heart rate, respiratory rate and SpO2 were monitored. Assessments of pain (VAS), nausea-vomiting, motor block, pruritus and sedation were recorded for 24 hr. RESULTS: No difference in pain or sedation was observed between groups. The 24 hr postoperative opioid consumption was 15.50 +/- 7.53 mg morphine and 555.10 +/- 183.85 micrograms fentanyl. Total bupivacaine 0.125% consumption was 58.00 +/- 30.14 ml in Group I and 101.05 +/- 36.77 ml in Group II. One patient in Group II complained of motor weakness in one leg. The incidence of nausea (Group I 45%, Group II 10% P < 0.05) and pruritus (Group I 30%, Group II 5% P < 0.05) was less in patients receiving fentanyl. CONCLUSION: Both methods were effective in the prevention of pain but, because of fewer side effects, fentanyl may be preferable to morphine.     

Severity and impact of pain after day-surgery

PURPOSE: To assess the intensity, duration and impact of pain after day-surgery interventions. Predictors of pain severity were also evaluated along with the quality of analgesic practices and patient satisfaction. METHODS: Eighty-nine consecutive day-surgery patients completed self-administered questionnaires before leaving the hospital and at 24, 48 hr and seven days after discharge. The survey instrument was composed of 0-10 pain intensity scales, selected items of the Brief Pain Inventory, of the Patient Outcome Questionnaire and of the Barriers Questionnaire. Analgesic intake in hospital and at home was recorded along with the use of other pain control methods. RESULTS: Forty percent of the patients reported moderate to severe pain during the first 24 hr after hospital discharge. The pain decreased with time but it was severe enough to interfere with daily activities in a substantial number of patients. The best predictor of severe pain at home was inadequate pain control during the first few hours following the surgery. More than 80% of the participants were satisfied with their pain treatment. However, one patient in four (25%) needed contact with a health care provider because of pain at home. Many patients (33% to 51%) reported that instructions about pain control were either unclear or non-existent on several aspects. Medication use was low overall. Thirty-two percent of the patients did not take any pain medication during the first 24 hr after discharge although almost half of them (46%) rated their pain > or = 4. The most common concerns patients had about using pain medication were fear of drug addiction and side effects. CONCLUSION: The severity and duration of pain after day-surgery should not be underestimated. Aggressive analgesic treatment during the hospital stay should be provided along with take-home analgesia protocols and comprehensive patient education programs.     

Inhibitors of tyrosine kinase

BACKGROUND AND OBJECTIVES: Neurolytic superior hypogastric plexus block has been shown to be safe and effective in selected cancer patients. A large cohort of patients was studied to evaluate the continued efficacy and safety of this block in cancer patients with advanced disease. METHODS: A total of 227 pelvic pain patients with gynecological, colorectal, or genitourinary cancer who experienced poor pain control due to either progression of disease or to untoward side effects were enrolled in this study during a 3-year period. All pain patients receiving oral opioids were eligible to participate. A bilateral percutaneous neurolytic superior hypogastric plexus block with 10% phenol was performed 1 day after a successful diagnostic block with 0.25% bupivacaine. RESULTS: All patients reported a visual analog scale (VAS) pain score of 7-10/10 before the block. A positive response to a diagnostic block was obtained in 159 patients (79%). Overall, 115 patients of the 159 patients who responded to a diagnostic block (72%, 95% confidence interval of 65-79%) had satisfactory pain relief (VAS < 4/10), 99 (62%) after one block, and 16 (10%) after a second block. The remaining 44 patients (28%) had moderate pain control (VAS 4-7/10) after two blocks and received oral pharmacological therapy and epidural analgesic therapy with good results. Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks. No additional blocks were required by patients who had a good response during a follow-up period of 3 months. No complications related to the block were detected. CONCLUSIONS: Neurolytic superior hypogastric plexus block provided both effective pain relief and a significant reduction in opioid usage (43%) in 72% of the patients who received a neurolytic block. Overall, this represents 51% of the patients enrolled in the study. Poor results should be expected in patients with extensive retroperitoneal disease overlying the plexus because of inadequate spread of the neurolytic agent.     

Obstetric analgesia using continuous epidural perfusion of bupivacaine, adrenaline, and fentanyl

OBJECTIVES: To determine the efficacy and complications of continuous epidural perfusion of bupivacaine, adrenaline and fentanyl in the relief of pain during first and second stage labour during vaginal birth. PATIENTS AND METHODS: Between January 1990 and March 1993 we used continuous epidural perfusion for control of pain during labor in 1307 women. The solution administered through an epidural catheter and maintained until expulsion was one 10 ml bolus of bupivacaine 0.25% with adrenaline 1:200,000 and fentanyl 25 micrograms followed by continuous perfusion of bupivacaine 0.0625% with adrenaline 1:200,000 and fentanyl 2 micrograms/ml at an infusion rate of 12 ml/h. When analgesia was insufficient, a bolus of local anesthetic was administered or a pudendal block was carried out. RESULTS: Ninety-two percent of the birthing women reported good analgesic effect during the first stage; for 7% the effect was fair and for 0.55% it was poor. During the second stage 88% reported satisfactory analgesia, and 8% fair or poor. Assessment was not possible for the remaining women, who underwent cesarean sections. Complications were few and easily controllable. CONCLUSIONS: Maintenance of epidural perfusion with 0.0625% bupivacaine with adrenaline 1:200,000 and fentanyl 2 micrograms/ml provides sufficient analgesia during all stages of childbirth.     

Effects of continuous epidural administration of fentanyl and morphine on postcesarean pain

We studied the effects of continuous epidural administration of fentanyl and morphine with bupivacaine for management of postcesarean pain. Eighteen patients received either bolus epidural administration of fentanyl 100 micrograms or morphine 3 mg with 0.5% bupivacaine 4 ml, followed by continuous infusion of fentanyl 33 micrograms.ml-1 with 0.17% bupivacaine or morphine 0.21 mg.ml-1 with 0.17% bupivacaine for 48 hours, respectively. Pain score was assessed at 0 h, 12h, 24h and 48h after leaving the operating room. Pain score increased significantly and progressively in the fentanyl group. In all cases pruritus was noted. Severe pruritus was observed in the morphine group significantly more than in the fentanyl group. The current results indicate that morphine may be preferable to fentanyl for postcesarean pain control using the present opioid doses.     

Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms?

Hydrocodone is a semisynthetic opioid with analgesic and antitussive properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400 mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120 patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo; however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables.     

Comparison of the fatty acid compositions in intraepithelial and infiltrating lesions of the cervix: part II, free fatty acid profiles

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.     

Biological role of SCC antigen

STUDY OBJECTIVE: To compare the duration of analgesia and incidence of side effects of three doses of intrathecal fentanyl (25 micrograms, 37.5 micrograms, 50 micrograms) with three doses of intrathecal sufentanil (5 micrograms, 10 micrograms, 15 micrograms). DESIGN: Randomized, double-blind study. SETTING: Labor suite of the Hospital of the University of Pennsylvania. PATIENTS: 60 ASA physical status I and II parturients in active labor who requested analgesia. INTERVENTIONS: Patients received one of the six doses of opioid diluted with normal saline to achieve a volume of 1.5 ml intrathecally. MEASUREMENTS AND MAIN RESULTS: Duration of analgesia, contraction pain, degree of pruritus, maternal blood pressure, maternal heart rate, fetal heart rate, Apgar scores, and neurologic and adaptive capacity scores were measured. There was no statistical difference among the doses of fentanyl in duration of analgesia. In addition, there was no statistical difference among the doses of sufentanil. The durations of analgesia for all doses of sufentanil were statistically longer than that for all doses of fentanyl. There was no difference among all the groups for maximal pruritus score. The duration of pruritus did not differ among doses of fentanyl or sufentanil; the duration of pruritus was significantly longer for sufentanil. All groups had a decrease in blood pressure. There was no difference among the groups in regard to the effect on the systolic or diastolic blood pressure. CONCLUSIONS: Intrathecal sufentanil produced analgesia of longer duration than fentanyl for all doses studied. The duration of pruritus with sufentanil was also longer.     

Correlation between motility of testicular spermatozoa, testicular histology and the outcome of intracytoplasmic sperm injection

Many studies have demonstrated the postoperative analgesic efficacy of fentanyl delivered i.v. by patient-controlled analgesia (PCA) devices at demand doses ranging from 10 to 50 microg, but none has sought to define the optimal fentanyl PCA dose. In this randomized, double-blind, multicenter study, we compared the safety and efficacy of three administered demand-dose sizes of fentanyl (20, 40, and 60 microg) in 150 patients after major surgery. Efficacy was dose-dependent; positive response rates (i.e., a global assessment score of "very good" or "excellent" and the absence of severe opioid adverse effects) were 42%, 52%, and 68% for the 20, 40, and 60 microg demand-dose groups, respectively, and were significantly higher in the 60 microg demand-dose group. The number of doses administered and missed attempts were significantly smaller in the 40 and 60 microg demand-dose groups compared with the 20 microg demand-dose group. This suggests that the 20 microg demand dose provided inadequate pain relief. Adverse respiratory events were more frequent and mean respiratory rates were significantly slower with the 60 microg demand dose, compared with the 20 or 40 microg demand doses. These results indicate that, of these three doses, the 40 microg demand dose was optimal for fentanyl PCA management of moderate to severe pain after major surgery. IMPLICATIONS: The postoperative analgesic efficacy of fentanyl delivered i.v. by patient-controlled analgesia devices has been demonstrated for demand doses ranging from 10 to 50 microg, but the optimal fentanyl dose remains unknown. In this randomized, double-blind study, we compared three demand dose sizes of fentanyl (20, 40, and 60 microg) and found that the 40 microg demand dose was the most appropriate for fentanyl patient-controlled analgesia management of postoperative pain.     

Anti asialoglycoprotein receptor antibodies and soluble interleukin-2 receptor levels as marker for inflammation in autoimmune hepatitis

Previous results using an amphibian model showed that systemic and spinal administration of opioids selective for mu, delta and kappa-opioid receptors produce analgesia. It is not known whether non-mammalian vertebrates also contain supraspinal sites mediating opioid analgesia. Thus, opioid agonists selective for mu (morphine; fentanyl), delta (DADLE, [D-Ala2, D-Leu5]-enkephalin; DPDPE, [D-Pen2, D-Pen5]-enkephalin) and kappa (U50488, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate; CI977, (5R)-(544alpha,744alpha,845beta)-N-methyl-N-[7-(1-p yrr olidinyl)-1-oxaspiro[4,5]dec-8yl]-4-benzofuranaceta mide++ + monohydrochloride) opioid receptors were tested for analgesia following i.c.v. administration in the Northern grass frog, Rana pipiens. Morphine, administered at 0.3, 1, 3 and 10 nmol/frog, produced a dose-dependent and long-lasting analgesic effect. Concurrent naltrexone (10 nmol) significantly blocked analgesia produced by i.c.v. morphine (10 nmol). ED50 values for the six opioids ranged from 2.0 for morphine to 63.9 nmol for U50488. The rank order of analgesic potency was morphine > DADLE > DPDPE > CI977 > fentanyl > U50488. These results show that supraspinal sites mediate opioid analgesia in amphibians and suggest that mechanisms of supraspinal opioid analgesia may be common to all vertebrates.     

Recurrence of inguinal hernia: ambulatory surgery under local anesthesia

In order to assess the feasibility of repair of a recurrent inguinal hernia in unmonitored local anaesthesia in an ambulatory set-up pain scores and data on patient satisfaction were obtained from 76 unselected patients after 79 consecutive operations. Median age was 63 years, and 25%- and 75% quartiles were 49 and 72 years respectively. All operations were conducted in local anesthesia. Three patients stayed in hospital overnight after the operation. Pain: After one, six and 28 days 27, 14 og 7% respectively had severe pain during function (cough and/or rising). Satisfaction: 82% were satisfied with ambulatory surgery in local anaesthesia, 82% were satisfied with the analgesic therapy (tenoxicam and methadone), but one third needed supplementary analgesics during the first week (acetaminophen was recommended). It is concluded, that ambulatory repair of a recurrent inguinal hernia in unmonitored local anaesthesia is a safe and cost effective alternative to operation in general or spinal anaesthesia.     

Pain therapy

NEW OPIOID ANALGESICS: Progress in pain reliet has recently been achieved with the introduction of new opioid analgesics such as tramadol and the pediatric preparation of codeine phosphate as well as powerful long-release opioids which can be administered per os, or percutaneously for transdermal fentanyl. CO-ANALGESICS: Other drugs, mainly antidepressants and anti-convulsants, can be usefully combined with analgesics. New serotonin uptake inhibitors and anticonvulsants (gabapentin and lamotrigin) have the advantage of better tolerance. None of these drugs has marketing approval in France for their pain relieving effects. The same is true for clonidine and neostigmine which, after spinal infusion, potentialize opioids and for ketamine which can relieve neuropathy pain by dissociative anesthesia. NEW ANTI-MIGRAINE DRUGS: New drugs have been developed for specific types of pain such as migraine. The new "triptans" are tolerated better than sumatriptan and is reimbursed by the national social security. REFRACTORY NEUROPATHY PAIN: Indications for electrical stimulation techniques conducted in a neurosurgery unit have been identified. Stimulators may be implanted in spinal or supra-spinal localizations. REGULATORY ASPECTS: New legislation has reorganized health care for pain relief in France. The new texts take into consideration personnel training, the health care network and progress in therapeutics.     

Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home

PURPOSE: The aim of this study was to evaluate the analgesic and adverse effects and the doses of methadone in comparison to morphine. PATIENTS AND METHODS: A prospective randomized study was performed in a sample of 40 patients with advanced cancer who required strong opioids for their pain management. Patients were treated with sustained-release morphine or methadone in doses titrated against the effect administered two or three times daily according to clinical need. Opioid doses, adjuvant medications, symptoms associated with opioid therapy, pain intensity, and pain mechanisms were recorded. The opioid escalation indices in percentage (OEI%) and milligrams (OEImg) were calculated. The effective analgesic score (EAS) that monitors the analgesic consumption-pain ratio was also calculated at fixed weekly intervals. RESULTS: differences in pain intensity were found. Patients treated with methadone reported values of OEI significantly less than those observed in patients treated with morphine. Seven patients in the methadone group maintained the same initial dosage until death, whereas only one patient in the morphine group did not require opioid dose escalation. A more stable analgesia in time in patients treated with methadone was shown by the low number of gaps in EASs reported. Symptom frequencies and intensities were similar in the two groups. CONCLUSION: Methadone is a drug of indisputable value in the treatment of cancer pain, and an unbalanced focus on the risks of inappropriate use rather than the benefits should not compromise the use of a relevant alternative to morphine in the management of cancer pain.