Intrathecal Cold Saline for the Relief of Intractable Pain

Cold saline was injected intrathecally for the relief of intractable pain in terminal cancer patients. Worthwhile relief was obtained in five out of seven patients. The procedure should be considered in the management of such cases when neurosurgical procedures have failed or are contraindicated and when patients have become addicted to, or their pain is unrelieved by, narcotics. There is still uncertainty as to whether cold or hypertonicity is the operative factor; we are more in favour of the latter view.     

The treatment of perinatal addiction. Identification,intervention, and advocacy.

Women of reproductive age who use and abuse psychoactive drugs and alcohol present a special challenge to primary care physicians. There are compelling medical reasons for identifying and intervening with pregnant women who are addicted or have alcoholism. The teratogenicity of all drugs of abuse and alcohol, the risk of infection with the acquired immunodeficiency syndrome (AIDS), and the potential for full recovery of a pregnant woman from addiction are some of the reasons that identification and intervention in the problem are indicated. Whether encountered in the clinic setting or in private practice, chemically dependent pregnant or postpartum women are usually responsive to appropriate physician interventions that include a detailed and caring confrontation- and advocacy-oriented support. Complex legal and ethical issues surround perinatal addiction including the role of toxicologic screening, reports to child welfare services, issues in noncompliance, and interdisciplinary case management.     

Should symptomatic menopausal women be offered hormone therapy?

Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.     

Should symptomatic menopausal women be offered hormone therapy?

Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.     

Pain relief in medical patients: does clinical judgment and prescribing knowledge suffice?

The aim of this study was to evaluate the quality of pain management in hospitalised patients. A cross-sectional study design that included all medical patients experiencing pain was used. Out of 167 patients hospitalized at the Department of Medicine at the University Hospital Zagreb, 41 patients were experiencing pain and 40 out of them received analgesics. Twenty-two out of 38 patients were treated for malignant pain, 16 for non-malignant pain, and 2 patients could not be classified. Adequate pain relief was reported in less than 25% of patients in both groups. Our study revealed under-prescribing of combination therapy, low utilization rates of strong opioids and prevailing "as needed" prescribing practice. In conclusion, unsatisfactory pain management in medical patients is often present if left solely to the clinical judgement and knowledge of the prescribing physician. Regular pain assessment, evidence-based guidelines, education and regular audits of implementation of these measures are a prerequisite for effective pain treatment, and should all be employed in patients experiencing pain.     

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.     

Can chronic pain be suppressed despite purported tolerance to narcotic analgesia?

Responsivity to acute nociceptive stimulation and the analgesic response to narcotic drugs was examined in rats exposed to an experimental model of chronic pain, i.e. $\text{Mycobacterium butyricum}$-induced adjuvant arthritis. The major findings are that (i) exposure to chronic pain alone causes hypo-algesia; this hypo-algesia can be attenuated by concurrent narcotics administration; (ii) chronic narcotics administration alone causes hyper-algesia; this hyper-algesia can be attenuated by concurrent exposure to chronic pain; (iii) the tolerance to narcotic analgesia which develops upon chronic narcotics administration in pain-free animals, need not occur in animals concurrently exposed to chronic pain. These findings support a recently proposed hypothesis on pain processing by the central nervous system, and may be suggestive of an effective treatment of chronic pain.     

Bioethics for clinicians: 11. Euthanasia and assisted suicide

Euthanasia and assisted suicide involve taking deliberate action to end or assist in ending the life of another person on compassionate grounds. There is considerable disagreement about the acceptability of these acts and about whether they are ethically distinct from decisions to forgo life-sustaining treatment. Euthanasia and assisted suicide are punishable offences under Canadian criminal law, despite increasing public pressure for a more permissive policy. Some Canadian physicians would be willing to practise euthanasia and assisted suicide if these acts were legal. In practice, physicians must differentiate between respecting competent decisions to forgo treatment, providing appropriate palliative care, and acceeding to a request for euthanasia or assisted suicide. Physicians who believe that euthanasia and assisted suicide should be legally accepted in Canada should pursue their convictions only through legal and democratic means.     

Effects of perceived patient demand on prescribing anti-infective drugs

BACKGROUND: Although patient demand is frequently cited by physicians as a reason for inappropriate prescribing, the phenomenon has not been adequately studied. The objectives of this study were to determine the prevalence of perceived patient demand in physician-patient encounters; to identify characteristics of the patient, physician and prescribing situation that are associated with perceived demand; and to determine the influence of perceived demand on physicians'' prescribing behaviour. METHODS: An observational study using 2 survey approaches was conducted in February and March 1996. Over a 2-day period 20 family physicians in the Toronto area completed a brief questionnaire for each patient encounter related to suspected infectious disease. Physicians were later asked in an interview to select and describe 1 or 2 incidents from these encounters during which perceived patient demand influenced their prescribing (critical incident technique). RESULTS: Perceived patient demand was reported in 124 (48%) of the 260 physician-patient encounters; however, in almost 80% of these encounters physicians did not think that the demand had much influence on their decision to prescribe an anti-infective. When clinical need was uncertain, 28 (82%) of 34 patients seeking an anti-infective were prescribed one, and physicians reported that they were influenced either "moderately" or "quite a bit" by perceived patient demand in over 50% of these cases. Of the 35 critical prescribing incidents identified during the interviews, anti-infectives were prescribed in 17 (49%); the reasons for prescribing in these situations were categorized. INTERPRETATION: This study provides preliminary data on the prevalence and influence of perceived patient demand in prescribing anti-infectives. Patient demand had more influence on prescribing when physicians were uncertain of the need for an anti-infective.     

Comparative Analgesic Activity of Levomepromazine and Morphine in Patients with Chronic Pain

Apart from its ability to potentiate the action of narcotics, levomepromazine, a phenothiazine derivative, was shown to possess its own analgesic activity comparable to that of morphine at a 3:2 dose relationship.In a double-blind crossover study of 18 patients suffering from chronic pain (cancer and arthritis), levomepromazine (15 mg.) was compared with morphine (10 mg.) and placebo. Three hours after intramuscular administration, levomepromazine proved to be significantly superior to placebo (p < .05) and indistinguishable from morphine. Evaluations of pain relief by estimations of changes in pain intensity were found to correlate well with evaluations based on recognition of pain relief exceeding 50%.The potent analgesic effect of levomepromazine was obtained at the price of excessive sedation. This, however, was considered an acceptable side effect in a patient suffering from chronic pain. These results provide encouragement in the quest for a non-addicting substitute for morphine.     

Medical practice opinion

To provide an effective continuum of the relief of severe carcinomatous pain with minimal side reactions, we initiated treatment with piroxicam (60 to 120 mg per day) and doxepin hydrochloride (25 to 225 mg per day). Of 30 patients presenting with severe pain of cancer of various origins, 7 continued to death with piroxicam and doxepin therapy. An additional 17 were successfully treated for 6 to 66 weeks with therapy reported here but, as disease progressed, required supplemental narcotics. The remaining six abandoned the use of piroxicam due to complications of therapy, which ranged from diarrhea to gastric perforation; serious complications were associated with patients'' failure to adhere to a prescribed regimen of sucralfate. Therapy with piroxicam and doxepin proved to be safe and efficacious.     

A randomized,placebo controlled,trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

BACKGROUND: Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. METHODS: This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone trade mark ) or an optically identical placebo injection of Intralipid trade mark and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. RESULTS: Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056) in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative period. Intraoperative ketorolac treatment significantly lowered (P = 0.027) pain scores and reduced the postoperative requirement for additional pain relief drugs. CONCLUSIONS: There was a lack of efficacy of preoperative sustained release betamethasone in reducing postoperative pain despite maintaining a therapeutic concentration during the postoperative period. Intraoperative Ketorolac did afford some short-term pain relief in the postoperative period and reduced the need for additional pain relief drugs.     

Tracking the opioid receptors on the way of desensitization

Opioid receptors belong to the super family of G-protein coupled receptors (GPCRs) and are the targets of numerous opioid analgesic drugs. Prolonged use of these drugs results in a reduction of their effectiveness in pain relief also called tolerance, a phenomenon well known by physicians. Opioid receptor desensitization is thought to play a major role in tolerance and a lot of work has been dedicated to elucidate the molecular basis of desensitization. As described for most of GPCRs, opioid receptor desensitization involves their phosphorylation by kinases and their uncoupling from G-proteins realized by arrestins. More recently, opioid receptor trafficking was shown to contribute to desensitization. In this review, our knowledge on the molecular mechanisms of desensitization and recent progress on the role of opioid receptor internalization, recycling or degradation in desensitization will be reported. A better understanding of these regulatory mechanisms would be helpful to develop new analgesic drugs or new strategies for pain treatment by limiting opioid receptor desensitization and tolerance.     

Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals

Buprenorphine has been widely used for post-operative analgesia in laboratory animals. Clinical efficacy has been demonstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to post-operative pain. This has resulted in recommendations of excessive dose rates and inappropriate clinical indications. Studies involving tests of the efficacy of buprenorphine for alleviating behavioural or other signs of tonic (post-surgical) pain provide a more appropriate estimation of the analgesic capabilities of the drug. However, buprenorphine also has major effects upon the behaviour of normal (unoperated) animals, and this makes assessments of efficacy difficult with some of the systems used for scoring clinical pain. Nevertheless, our most recent studies of the effects of buprenorphine upon pain-related behaviours in rats support the view that it is an effective post-operative analgesic. This short review critically reappraises the role of buprenorphine in this capacity and discusses a rational approach to the relief of pain in laboratory animals. We conclude that buprenorphine remains a valuable agent for pain relief in a wide range of animal species when used in an appropriate manner.     

Documenting wife abuse: a guide for physicians

An estimated 12% to 30% of women are assaulted by their male partners at least once during the relationship. Therefore, in their everyday practice, physicians are likely to encounter women who have suffered domestic abuse. The authors define wife abuse, outline epidemiologic aspects and discuss common signs and symptoms. In cases of suspected or confirmed abuse, it is very important for physicians to document the details of the injuries, the patient visit, any treatment and follow-up as well as to screen for associated conditions and ensure that any samples taken are not tampered with. When asked to disclose information by police or courts, physicians need to know when they are obliged to submit copies of their patients'' medical records, when patient consent is required, what information should be divulged and how to defend this information in court. The authors present information about the necessary, relevant and appropriate evidence to be collected and documented for both medical and legal purposes. They also discuss the criminal justice system and the role of physicians in legal proceedings concerning wife abuse.     

Pain centers--organization and outcome.

Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain.     

Pharmacogenetics: Implications for drug development,patients and society

Clinical diagnosis and prescribing is a highly sophisticated art, requiring many years of training. Despite this, the response of individual patients to medicines (where efficacy and safety have been proven in large clinical studies) can still be somewhat variable. Knowledge of the likely response of an individual patient to a medicine will enable physicians to select the most effective and well-tolerated treatment for that patient. Pharmacogenetics is the use of genetic science and technology to provide new insights on the likely response to a particular medicine. (This contrasts with the more conventional use of genetics to elicit information about diseases.) Pharmacogenetic medicine response profiles could take the form of either gene-specific profiles, which will determine the gene variants that affect the mode of action and the metabolism of the medicine, or abbreviated single nucleotide polymorphism profiles, which are correlated with medicine-related phenotypes. In general, pharmacogenetic medicine response profiles will be unlikely to provide additional information about the patient's disease or predict any other diseases. The ethical, legal and social issues associated with medicine response profiles are clearly of a quite different magnitude from those associated with the gene-specific tests for disease.