Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain.

This open-label, multicenter study assessed the efficacy and tolerability of conversion to once-daily OROS hydromorphone from previous opioid agonist therapy in patients with chronic cancer pain. Patients were stabilized on their previous therapy before conversion at a 5:1 ratio of morphine sulfate to hydromorphone hydrochloride. The OROS hydromorphone dose was titrated over 3 - 21 days to achieve effective analgesia and was maintained for up to 14 days. Efficacy was assessed using the Brief Pain Inventory (BPI). Adverse events and vital signs were monitored. Dose stabilization was achieved in 119 of the 127 (94%) patients who received the study medication; in 77%, stabilization was achieved with no titration steps. Mean BPI pain intensity ratings and BPI pain interference scores decreased significantly after OROS hydromorphone treatment compared with pretreatment values. Mean pain-relief level remained stable after conversion and throughout treatment with OROS hydromorphone. Adverse events were as expected for cancer patients receiving opioid agonists. There were no clinically significant changes in vital signs.

Once-daily OROS hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study.

BACKGROUND: The use of opioid analgesics for patients with chronic nonmalignant pain is becoming more widely accepted, and long-acting formulations are an important treatment option. AIM: To assess conversion to extended-release OROS hydromorphone from previous stable opioid agonist therapy in patients with chronic nonmalignant pain of moderate-to-severe intensity. METHODS: In this open-label multicentre trial, patients were stabilised on their previous opioid therapy before being switched to OROS hydromorphone at a ratio of 5 : 1 (morphine sulphate equivalent to hydromorphone hydrochloride). The OROS hydromorphone dose was titrated over 3-16 days to achieve effective analgesia, and maintenance treatment continued for 14 days. RESULTS: Study medication was received by 336 patients; 66% completed all study phases. Stabilisation of OROS hydromorphone was achieved by 94.6% of patients, the majority in two or fewer titration steps (mean time, 4.2 days). Mean pain intensity scores, as determined by the Brief Pain Inventory, decreased during OROS hydromorphone treatment (p

An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM).

BACKGROUND: The randomized clinical trial of implantable drug delivery systems (IDDS) plus comprehensive medical management (CMM) versus CMM alone showed better clinical success at 4 weeks for IDDS patients. This 'as treated' analysis assessed if improvements in pain control, drug toxicity and survival were maintained over time. PATIENTS AND METHODS: We compared those who received IDDS with those who did not receive IDDS (non-IDDS). All patients had Visual Analogue Scores (VAS) for pain > or =5/10 on at least 200 mg morphine or equivalent daily. RESULTS: At 4 weeks, 46 of 52 (88.5%) IDDS patients achieved clinical success compared with 65 of 91 (71.4%; P=0.02) non-IDDS patients, and more often achieved > or =20% reduction in both pain VAS and toxicity [35 of 52 (67.3%) versus 33 of 91 patients (36.3%); P=0.0003]. By 12 weeks, 47 of 57 (82.5%) IDDS patients had clinical success compared with 35 of 45 (77.8%; P=0.55) non-IDDS patients, and more often had a > or =20% reduction in both pain VAS and toxicity [33 of 57 (57.9%) versus 15 of 45 patients (33.3%); P=0.01]. At 12 weeks the IDDS VAS pain scores decreased from 7.81 to 3.89 (47% reduction) compared with 7.21 to 4.53 for non-IDDS patients (42% reduction; P=0.23). The 12 week drug toxicity scores for IDDS patients decreased from 6.68 to 2.30 (66% reduction), and for non-IDDS patients from 6.73 to 4.13 (37% reduction; P=0.01). All individual drug toxicities improved with IDDS at both 4 and 12 weeks. At 6 months, only 32% of the group randomized to CMM and who did not cross over to IDDS were alive, compared with 52%-59% for patients in those groups who received IDDS. CONCLUSIONS: IDDS improved clinical success, reduced pain scores, relieved most toxicity of pain control drugs, and was associated with increased survival for the duration of this 6 month trial.

A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain.

BACKGROUND: Nerve injury results in increases in spinal glutamate, which opens the NMDA ionophore channel, causing an influx of calcium. A glycine-binding site must be occupied for the channel to open. GV196771 is a selective antagonist of the glycine-binding site of the NMDA ionophore. OBJECTIVE: To determine the efficacy of GV196771 in subjects with chronic neuropathic pain in a proof-of-concept study. METHODS: With informed consent, 63 subjects (31 placebo, 32 GV196771) with neuropathic pain (diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, or peripheral nerve injury), a visual analogue score averaging > or =30 mm during the screening period, and a well-defined primary area of mechanical allodynia were recruited for the study. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study design was utilized. Subjects came to the research center for a total of five visits over a 21-day period, which consisted of a 14-day treatment period followed by a 7-day washout period. Spontaneous and evoked pain scores, mechanical sensory testing, quantitative sensory testing, Short Form McGill Pain Questionnaire, patient global satisfaction, and safety assessments were made during the study. RESULTS: There was no significant effect of GV196771 on spontaneous or evoked pain, quantitative sensory testing, or patient global satisfaction. There was a significant effect of GV196771 on the area of dynamic and static allodynia on days 7 and 14. The overall incidence of adverse events during treatment was similar for GV196771 (56%) and placebo (71%). The incidence of drug-related adverse events during treatment was higher for placebo (42%) than GV196771 (28%). CONCLUSIONS: Although the glycine antagonists show anti-hyperalgesic action in animal models of neuropathic pain, GV196771 does not appear to be an effective treatment in subjects with chronic neuropathic pain. This may be due to insufficient penetration of GV196771 to central sites of action, differences between the human and animal glycine receptors, or differences between neuropathic pain in animal models and humans.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part II.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus simultaneously on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain. This part examines pharmacologic methods.

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part I.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care, and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain.

The anticoagulated patient.

The expanded role for antiplatelet drugs and anticoagulant therapy has resulted in more surgical patients receiving these medications during the perioperative period. The risk of developing a spinal hematoma (epidural, subdural, or subarachnoid) remains exceedingly small in most patients despite receiving these therapies. Despite the low incidence, potentially devastating neurologic sequelae often occur in the patient who develops a spinal hematoma. Irreversible paresis/paralysis can result despite excellent emergent care. Management of the patient with an abnormal bleeding history or other hemostatic abnormality must be individualized. Each situation is unique and should be considered in its totality. Certainly, patients receiving fibrinolytic agents such as streptokinase or patients with diffuse hemorrhagic problems (eg, disseminated intravascular coagulation) should avoid regional anesthesia and spinal blocks (27,28). Other situations are often less clear and require appropriate judgments by the anesthesiology consultant as to the risk/benefit ratio. Issues that must be entered into the equation include degree of hemostatic abnormality present, surgery anticipated, what if any anticoagulation is planned postoperatively, emergent versus elective surgery, skill of the regional anesthesiologist, patient desires, and associated medical abnormalities. Clearly, it is of extreme importance that documentation be thorough and include knowledge of the associated risks and why the risks are acceptable in the particular patient. This documentation provides good medical information and can be helpful should a medicolegal issue arise. This documentation should include informed consent, which is thoroughly explained to the patient and/or family. It is unlikely that anesthesiologists will be able to develop exact numbers on the incidence of spinal hematomas because of the rarity of this event. It remains extremely important that practitioners continue to report the occurrence of such hematomas, so that information can be gleaned from their experience. The experience of practitioners with LMWH and central neuraxial block, described above, currently is providing us with important information, which may ultimately affect the way we practice. Without case reporting of this information, the knowledge would remain unobtainable.

Comparison of the efficacy of epidural morphine given by intermittent injection or continuous infusion for the management of postoperative pain.

BACKGROUND AND OBJECTIVES: To compare the effectiveness and side effects of epidural morphine sulfate (MSO4), delivered by continual infusion or intermittent bolus. METHODS: Thirty patients undergoing upper abdominal surgery were randomized into two equal groups to receive MSO4 through a thoracic epidural catheter by one of two methods. Group 1 patients received an initial bolus of morphine (0.07 mg/kg) at the end of surgery, followed by injections of 2-5 mg morphine into the epidural catheter on demand. Patients in group 2 received an initial bolus of morphine (0.03 mg/kg) during surgical peritoneal closure and were immediately started on an infusion of 0.01% morphine at 5 mL/hour (0.5 mg/hour). The infusion dose was titrated from 0.2 to 1.0 mg/hour, dependent on side effects. Outcome measurements included pulmonary function studies, arterial blood gases, morphine plasma levels, pain relief scores, global evaluations, and side effects. RESULTS: No difference existed between groups in forced vital capacity, forced expiratory volume in 1 second, or in arterial blood gas measurements. Side effects were similar in both groups. Respiratory depression was not seen in either group. Group 2 reported significantly better analgesia than group 1 on postoperative days 1 and 2 (P < .01). Peak plasma morphine levels for group 1 were significantly higher than the steady state plasma morphine levels for group 2 (P < .05). CONCLUSIONS: Continuous epidural infusion provides better analgesia without increased side effects for postoperative pain when compared with an intermittent (or demand) bolus technique.

Epidural clonidine treatment for refractory reflex sympathetic dystrophy.

BACKGROUND: Intraspinally administered alpha 2-adrenergic agonists may relieve pain in sympathetically maintained pain (SMP) syndromes, such as reflex sympathetically dystrophy (RSD), by spinal, peripheral, and central nervous system actions. This study examined analgesic efficacy and side effects of epidurally administered clonidine in patients with severe, refractory RSD. METHODS: Twenty-six patients with severe chronic pain consistent with RSD were studied in a randomized, blinded, placebo-controlled design. Cervical or lumbar epidural catheters were inserted for patients with upper or lower extremity RSD, respectively, and patients received, in random order on three consecutive days, epidural injection of clonidine, 300 or 700 micrograms, or placebo. Pain (by visual analog score (VAS) and McGill Pain Questionnaire), sedation, blood pressure, and heart rate were monitored at specified intervals for 6 h after injection. Patients who responded to clonidine, but not placebo, then entered a trial of open-label, continuous epidural infusion of clonidine (10-50 micrograms/h). RESULTS: Clonidine, but not placebo, caused pain relief, sedation, and decreased blood pressure and heart rate after bolus epidural injection. The smaller clonidine dose (300 micrograms), produced pain relief and decreases in blood pressure and heart rate similar to those of the 700 micrograms dose, but with less sedation. Epidural clonidine was infused for a mean of 43 days in 19 patients at a mean rate of 32 micrograms/h for sustained analgesia. CONCLUSIONS: Transdermal clonidine has been demonstrated to produce analgesia in the area surrounding its application site in patients with SMP. The current study indicates that extensive analgesia may be obtained by epidural administration. Sedation and hypotension may limit bolus epidural clonidine administration for RSD. The role for chronic epidural infusion of clonidine has not yet been established.

Early experience with high thoracic epidural anesthesia in outpatient submuscular breast augmentation.

High thoracic epidural anesthesia was administered by anesthetists in 20 patients undergoing submuscular breast augmentation. An average of 12 ml of 2% lidocaine was instilled after sedation with midazolam, 2-6 mg. The augmentation procedure averaged 90 minutes. In 3 patients, the block developed more rapidly on one side than the other, but soon became symmetrical in all; additional subcutaneous infiltration of lidocaine was necessary in 1 patient because of infraclavicular pain; ephedrine, 10 mg was needed in 2 patients to treat hypotension (greater than 20% decrease in blood pressure). Three patients felt infraclavicular pressure; 1 had a brief sensation of breathlessness; 3 had nasal stuffiness from Horner's syndrome associated with the block; none developed headache, back pain, or paresthesias; and 3 had postoperative nausea. The average time from the end of the procedure to patient discharge was 96 minutes. In this limited series, high thoracic epidural anesthesia for submuscular breast augmentation was extremely satisfactory.