Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain.

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study.

To compare the effectiveness and safety of controlled-release (CR) oxycodone tablets with immediate-release (IR) oxycodone in patients with chronic cancer pain, a multicenter, randomized, double-blind, parallel-group study was performed in 111 patients with cancer pain. Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry. Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days. No titration or supplemental analgesic medications were permitted. The mean (+/- SE) baseline pain intensity (0 = none, 1 = slight, 2 = moderate, 3 = severe) was 1.5 +/- 0.1 for the CR oxycodone-treated group and 1.3 +/- 0.1 for the group given IR oxycodone (P > 0.05). The 5-day mean pain intensity was 1.4 +/- 0.1 and 1.1 +/- 0.1 for the CR and IR groups, respectively (P > 0.05). Discontinuation rates were equivalent (33%). There was no significant difference between treatment groups in the incidence of adverse events. This study demonstrates that cancer pain patients given 6 to 12 tablets or capsules of fixed-dose combination analgesics can be equally well treated with CR oxycodone administered every 12 hr or IR oxycodone four times daily at the same total daily dose. CR oxycodone offers the benefits of twice daily dosing.

Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain.

PURPOSE: This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain. PATIENTS AND METHODS: Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent). RESULTS: Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION: CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.

Infrared laser diode irradiation has no behavioral or biochemical effect on pain in the sciatic nerve ligation-induced mononeuropathy in rat.

The aim of this study was to evaluate the effect of acute and repeated (5 days) treatment with various types of infrared (IR) diode lasers and probes (single- vs cluster-beam) on the pain response in rats with peripheral mononeuropathy produced by sciatic nerve ligation. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the mid-thigh was surgically exposed to reveal the sciatic nerve, around which four ligatures were loosely tied. On postoperative day 5, the skin over the sciatic nerve lesion was subjected to a 30-min daily local exposure from a 904-nm IR diode laser (700 Hz, average output power 10 mW) with a single-beam probe, a 830-nm IR diode laser (700 Hz) with either a single-beam (average output power 50 mW) or cluster-beam probe (average output power 15 mW), or placebo for 5 consecutive days. Two pain responses (foot-withdrawal time and the hind-paw elevation time) were measured on both sides using the radiant heat method on days 5 and 9. In addition, cold allodynia was measured on day 9 of treatment by placing the rats on a chilled metal plate (4 degrees C) and measuring the duration of elevation of either of the hind paws. On day 9, the animals were sacrificed for collection of the samples of brain and lumbar spinal cord for the determination of the tissue concentrations of dynorphin A1-8-like immunoactivity (DYN) using specific radioimmunoassay (RIA). The hind-paw withdrawal and elevation times on the right side in all groups subjected to the various methods of IR laser irradiation did not differ significantly as compared with the placebo-treated group when measured on days 5 and 9 after surgery. No statistically significant differences in withdrawal response and elevation time of the unaffected left hind paw were noted either. The measurement of cold allodynia similarly failed to reveal any effect in laser-treated groups versus placebo. The RIA analysis found that tissue concentrations of DYN were significantly elevated in the spinal cord ipsilaterally to the ligation side, as compared with the contralateral side, in all rats with sciatic nerve ligation. All modalities of IR diode laser treatment did not produce any significant difference in the brain and spinal cord level of DYN on postoperative day 9 in all treatment groups. It is concluded that repeated IR diode laser treatment did not reduce hyperalgesia induced by sciatic nerve ligation in rats.

The effects of neurokinin A, neurokinin B, and eledoisin on substance P analysis.

Commercial sources for neuropeptide radioimmunoassays have made this sensitive tool available to clinical investigators for monitoring the potential involvement of neuropeptides in pain modulation. We measured substance P-like immunoreactivity in the plasma, saliva, and pericardial fluid of subjects with and without pain (chronic and acute) to determine if substance P levels are altered. Some recent studies have suggested that substance P in various body fluids may be a correlate of chronic pain. To test this correlation it is important to ensure that the assay is measuring what it was designed to measure. Therefore, the influence of three tachykinins on the analysis of substance P concentrations was assessed with a commercially available radioimmunoassay kit. A small (approximately 2 to 6%), apparently nonspecific elevation in measured substance P was found when alpha-neurokinin, beta-neurokinin, or eledoisin was incubated with substance P and its antibody. Our results also indicate an apparent specific affinity of the substance P antibody for alpha-neurokinin (above 1,000 pg/ml) and beta-neurokinin (above 5,000 pg/ml). Substance P levels in the body fluids we tested ranged from 0.47 to 62.88 pg/mg protein (47.4 to 230.8 pg/ml). Levels of the tested tachykinins have not been determined in body fluids. If alpha-neurokinin or beta-neurokinin is found to be present in high concentrations in these fluids, this commercially available substance P kit may overestimate substance P levels. The concentrations of tachykinins necessary to interfere specifically with the assay are 10- to 100-fold higher than substance P in body fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between cigarette smoking and chronic low back pain.

This study investigated the extent to which habitual cigarette smoking relates to physical and psychological indices of chronic pain. From a review of patient records, 54% of back pain patients referred for treatment of their pain admitted to smoking cigarettes. Response from a smoking questionnaire showed that 57% of the patients who smoked reported having a need to smoke when they were in pain. Most patients (91%), however, believed that smoking had no effect on their pain intensity. When smoking and nonsmoking back pain patients were compared, the smokers showed significantly higher levels of emotional distress, they tended to remain inactive, and they relied on medication more often than the nonsmoking patients. The results further suggest that pain patients are at risk for increasing smoking behavior when they are experiencing periods of heightened pain intensity.

Intrapleural analgesia for post-thoracotomy pain and blood levels of bupivacaine following intrapleural injection.

An epidural type catheter was placed in the pleural space under direct vision before the closure of the chest in 24 patients who underwent thoracotomy for various types of lung or aortic surgery. All patients received intrapleural injections of 20 ml of 0.5 per cent bupivacaine with or without epinephrine as initial pain therapy. Patients also received subsequent doses of a similar volume of 0.375 per cent bupivacaine with epinephrine 1:200,000 up to four times a day for a maximum duration of seven days. Good pain relief was achieved in patients who underwent lateral and posterior thoracotomies. No pain relief was achieved in patients who underwent anterior thoracotomy or in patients in whom there was excessive bleeding in the pleural space. Bupivacaine blood concentrations were measured in 11 patients following the initial dose of 20 ml of 0.5 per cent bupivacaine (with epinephrine 1:200,000 in five of the 11 patients). The mean peak plasma concentration of bupivacaine when used with epinephrine was 0.32 +/- 0.02 microgram.ml-1. The mean peak plasma concentrations of bupivacaine when used without epinephrine was 1.28 +/- 0.48 microgram.ml-1. Our present data show that intrapleural analgesia is useful in the management of postoperative pain in patients who undergo thoracotomy. Our data also show that there is a significant decrease in peak plasma concentrations of bupivacaine when epinephrine is added to the solution (P less than 0.05).

Typical and atypical presentation of malignant hyperpyrexia in nonwhite patients.

Two cases are presented of malignant hyperthermia in black patients. One patient developed signs of malignant hyperthermia during general anesthesia that was successfully treated with dantrolene sodium and cooling. A second patient was retrospectively diagnosed as having an atypical variant of malignant hyperthermia secondary to heat stroke and general anesthesia; this patient subsequently died. These cases illustrate that malignant hyperthermia can occur in blacks despite the very low incidence of this syndrome in nonwhite patients.

The effect of intentional hemodilution on P50.

Ten patients (Group I) scheduled for major vascular surgery received banked blood and twelve patients (Group II) also scheduled for major vascular surgery were administered intentional hemodilution with autologous blood. Both groups of patients were studied to determine the effects of banked blood and autologous blood respectively on P50. The mean pre-operative P50 for Group I and Group II patients were 26.2 mmHg and 26.3 mmHg respectively. The mean postoperative P50 for Group I and Group II patients were 24.7 mmHg and 28.4 mmHg respectively. There was a significant increase in P50 in patients (Group II) who received autologous blood when compared with Group I patients who received banked blood (p less than 0.001). Our data on P50 in Group I patients who received banked blood showed that there was a significant decrease confirming the results of previously published studies. The Authors conclude that intentional hemodilution is an efficacious alternative technique to banked blood administration for patients undergoing major vascular surgery.

Pre-treatment with somatostatin in the anaesthetic management of a patient with carcinoid syndrome.

Carcinoid syndrome produces flushing, bronchoconstriction and gastrointestinal hypermotility secondary to serotonin, histamine, bradykinin and prostaglandin release. A variety of drugs, foods and anaesthetic agents may provoke this syndrome. Under anaesthesia, the flushing produced may be associated with acute hypotension and cardiovascular collapse; this phenomenon is called a carcinoid crisis. Recently, somatostatin analogue has been used successfully to treat intraoperative carcinoid crisis. In this report, we present a 66-year-old lady with carcinoid syndrome who was pre-treated with 50 micrograms somatostatin analogue IV and IM prior to surgical manipulation. The anaesthetic course was relatively uneventful and the patient did well postoperatively.

Anxiety and postoperative recovery in ambulatory surgery patients.

There has been a growing trend toward one-day ambulatory surgery. Unfortunately, there has been little research evaluating how patients recover at home after one-day surgery. This study examined the relationship between preoperative anxiety and postoperative recovery in ambulatory surgery patients. Fifty women who were scheduled for a laparascopy completed a series of questionnaires on the day before surgery and on each of three days after surgery. One month after surgery, the patients were telephoned and reported on their recovery. The surgeon rated each patient on their estimated degree of anxiety and length of recovery. The results showed that preoperative anxiety partially predicted the patients' psychological and physiological reaction to surgery. Identification of those patients who show high anxiety and distress may help to prevent postoperative complications. These patients may benefit from patient education and psychological interventions to decrease their fears and anxiety and they may benefit from more intensive observation periods following their surgery.

Effects of time-limited vs unlimited compensation on pain behavior and treatment outcome in low back pain patients.

A common theme in the pain literature is that worker's compensation reinforces pain behavior and adversely influences treatment outcome of chronic pain patients. This study compared 110 chronic low back pain males divided into three groups: 44 receiving no compensation, 27 receiving time-limited worker's compensation, and 39 receiving unlimited social security disability benefits. All patients participated in a multimodal treatment program (e.g. nerve blocks, transcutaneous electrical nerve stimulation, relaxation training, biofeedback). Physician ratings of pain behavior and self-report measures of pain characteristics, activity level, and medication intake were gathered pretreatment; self-report measures were collected again approximately one year following treatment. The results showed disability patients to have a higher percentage of physician rated symptom dramatization and pain behavior and a greater usage of medication compared with the non-compensation and time-limited worker's compensation patients. At follow-up, no between group differences were found on measures of pain intensity, medication usage and activity. In general, however, more worker's compensation and non-compensation patients who were initially not working had returned to work at the time of follow-up compared with the disability patients. These results suggest that time-limited compensation may not affect treatment outcome or interfere with return-to-work chances while unlimited compensation may adversely influence the probability that patients will return to work. These findings support the notion that worker's compensation patients receiving time-limited financial benefits do not necessarily represent a 'problem' subgroup of chronic pain patients.

Hazards in operative management of patients with systemic mastocytosis.

During the past two years, six patients with systemic mastocytosis have required general or regional anesthesia for operative correction of various surgical problems. Mastocytosis constitutes an extremely difficult problem in diagnosis and management. A large experience with patients with mastocytosis in the Vanderbilt Medical Center in the last decade has enhanced awareness of this disorder and increased its early recognition. The hazardous problems of systemic mastocytosis and the difficulties of its diagnosis and management are summarized and focussed on the increased hazard of those patients with this disease who require various surgical operations. Close collaboration between anesthesiologists, surgeons, and internists in this medical center in the past two years has made it possible to carry six of these patients through anesthesia, operation, and the postoperative period safely and without fatality.