Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS

CONTEXT: Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available. OBJECTIVE: To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients. DESIGN: Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo. SETTING: Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities. PATIENTS: Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option). INTERVENTIONS: Standardized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks. MAIN OUTCOME MEASURE: Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily. RESULTS: Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99). CONCLUSIONS: In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.     

Potential neuroprotective therapy for glaucomatous optic neuropathy

Although mexiletine, an antiarrhythmic with local anesthetic properties, has been reported to relieve discomfort in diabetic neuropathy, its usefulness in the treatment of HIV-related painful peripheral neuropathy (PPN) has not been determined. The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine (maximum dose, 600 mg/day) or placebo for 6 weeks, followed by the alternative intervention for 6 weeks after a 1-week washout period. The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug, 16 of whom were crossed-over to receive the alternate agent. No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo, irrespective of the order in which the agents were received. Comparing the mean individual daily pain scores for each phase of study, 5 patients (31%) had significantly less pain while receiving mexiletine compared with their response to placebo, 5 patients (31%) had significantly less pain while receiving placebo, and no difference was noted in 6 patients (38%). Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo. Dose-limiting adverse events occurred in 39% of those receiving mexiletine, but only 1 patient (5%) discontinued placebo. Mexiletine was only modestly well tolerated despite its relatively brief period of administration, and no evidence was found to support its benefit in HIV-related PPN. Although a first-drug effect was not demonstrated, a powerful placebo effect was seen in some patients.     

Mexiletine. A review of its therapeutic use in painful diabetic neuropathy

Mexiletine is an orally active local anaesthetic agent which is structurally related to lidocaine (lignocaine) and has been used for alleviating neuropathic pain of various origins. Mexiletine has been evaluated in several randomised, placebo-controlled trials in patients with painful diabetic neuropathy. The drug decreased mean visual analogue scale (VAS) pain ratings in all studies that used this measure, although in only 2 studies was this effect significantly greater than the often substantial responses seen with placebo. The clinical significance of these decreases is not clear. Statistically significant (vs placebo) reductions in VAS pain ratings were observed in 16 patients receiving mexiletine 10 mg/kg/day for 10 weeks in 1 study and in nocturnal (but not diurnal) pain in 31 patients receiving mexiletine 675 mg/day for 3 weeks in another. Retrospective analysis of another study revealed that mexiletine recipients (225 to 675 mg/day) who described their pain as stabbing, burning or formication on the pain-rating-index-total instrument of the McGill Pain Questionnaire, experienced statistically significant reductions in VAS pain scores after 5 weeks, compared with placebo recipients. Mexiletine generally did not have a significant influence on the quality of sleep in patients with diabetic neuropathy. In Japanese patients, statistically significant reductions in subjective pain ratings were achieved with mexiletine 300 mg/day in 1 study and with 450 mg/day in a further study. In controlled trials, the frequency of adverse events in patients receiving mexiletine for painful diabetic neuropathy ranged from 13.5 to 50%. Gastrointestinal complaints, of which nausea was the most frequent, were the most common adverse events in mexiletine recipients. Central nervous system complaints were uncommon, but included: sleep disturbance, headache, shakiness, dizziness and tiredness. Serious cardiac arrhythmias have not been reported in patients receiving mexiletine for painful diabetic neuropathy; however, transient tachycardia and palpitations have been reported. There are significant differences in the metabolism of mexiletine between people who have cytochrome P450 2D6 [CYP2D6; extensive metabolisers (EMs)] and those who lack this isoenzyme [poor metabolisers (PMs)]. EMs, but not PMs, are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g. quinidine). Moreover, mexiletine inhibits CYP2D6-mediated metabolism of metoprolol and cytochrome P450 1A2-mediated metabolism of theophylline. Phenytoin and rifampicin (rifampin) induce the metabolism of mexiletine. Clearance of mexiletine is impaired in patients with hepatic, but not renal, dysfunction. Hence, dosage adjustments may be necessary in patients with liver disease. CONCLUSIONS: Tricyclic antidepressants (TCAs) are the agents of choice for painful diabetic neuropathy; however, they are ineffective in approximately 50% of patients and are generally not well tolerated. Mexiletine is an alternative agent for the treatment of painful diabetic neuropathy in patients who have not had a satisfactory response to, or cannot tolerate, TCAs and/or other drugs.     

Prevention of transurethral catheter-induced urinary tract infection

We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system.     

Low dose amitriptyline in ankylosing spondylitis: a short term, double blind, placebo controlled study

OBJECTIVE: To define the effect of low dose amitriptyline on fatigue, pain, and stiffness in patients with ankylosing spondylitis (AS). METHODS: One hundred consecutive patients with AS were randomized to receive low dose amitriptyline up to 30 mg nightly or placebo for 2 weeks. Patients were assessed by the Bath Ankylosing Spondylitis Disease Activity (BASDAI) and Functional (BASFI) Indices pre and post-treatment. RESULTS: Eighty-eight patients (44 amitriptyline, 44 placebo) completed the study. Eight (5 amitriptyline, 3 placebo) stopped treatment because of side effects (e.g., drowsiness, dryness of mouth) and 4 provided insufficient data. Compared to placebo, the patients taking amitriptyline showed significantly greater improvement in restful sleep (66 vs 20%; p < 0.001) and their disease activity scores [BASDAI amitriptyline 1.18 (23%) vs placebo 0.52 (10%); p = 0.024]. All other variables showed a trend to greater improvement by amitriptyline, although the differences were not statistically significant. CONCLUSION: (1) In a 2 week study, low dose amitriptyline significantly improved sleep in AS and was well tolerated; (2) as defined by BASDAI, there was a significant reduction in disease activity with amitriptyline; (3) compared to placebo, there was a nonsignificant trend toward improvement in function; and (4) in spite of improvement in pain, fatigue, and sleep with amitriptyline, stiffness was not increased.     

Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial

CONTEXT: Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. DESIGN: Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. SETTING: Outpatient clinics at 20 sites. PATIENTS: The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale. INTERVENTION: Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. MAIN OUTCOME MEASURES: The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results. RESULTS: Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06). CONCLUSION: Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.     

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs

BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.     

A mammographic evaluation of the morphostructural variations of the breast during hormone-replacement therapy in the postmenopause

OBJECTIVE: To compare i.v. ketorolac with i.v. prochlorperazine as the initial treatment of migraine headaches in the ED. METHODS: A prospective, double-blind comparison study was performed, using a convenience sample of 64 patients suffering from migraine headaches presenting to the ED at a tertiary care university teaching hospital. Patients were randomly assigned to receive either 10 mg of prochlorperazine i.v. or 30 mg of ketorolac i.v.. Patients scored the severity of their headaches using a 10-cm visual analog pain scale. An initial mark was made on the scale at the time of entry into the study and later another mark was made on a new unmarked pain scale 1 hour after medication administration. Changes in pain scores within each treatment group and between groups were analyzed using the Wilcoxon rank sum test. RESULTS: Prior to treatment, the patients assigned to receive prochlorperazine had a median score of 9.2 cm (mean +/- SD pain score of 8.3 cm +/- 2.1 cm), while the patients receiving ketorolac had a median score of 9.0 (mean pain score of 8.4 cm +/- 1.7 cm). There was no significant difference between the pain scores of the participants in the 2 groups prior to treatment (p = 0.80). One hour after medication administration, the patients in the prochlorperazine group had a median score of 0.5 cm (mean 2.1 +/- 3.2 cm), while those patients receiving ketorolac had a median pain score of 3.9 (mean 4.0 +/- 3.3 cm). The decrease in pain score was significant for both groups of patients (p = 0.0001). The change in pain score for the patients in the prochlorperazine group (median 7.1) was significantly greater than the change in pain score for the patients in the ketorolac group (median 4.0; p = 0.04). CONCLUSION: Although both drugs were associated with a significant reduction in pain scores, benefit over a placebo agent was not tested. Furthermore, the patients who received prochlorperazine i.v. for migraine headaches had a statistically significant greater decrease in their pain scores than did those receiving ketorolac i.v.     

Peripheral sensory nerve dysfunction in children and adolescents with type 1 diabetes mellitus

The aim of the present study was to investigate peripheral sensory nerve function in diabetic children and adolescents without neurological symptoms. Ninety-two children and adolescents with Type 1 (insulin-dependent) diabetes mellitus (mean +/- SD age: 14.2 +/- 2.1 years, diabetes duration: 5.8 +/- 3.0 years) and 80 healthy control subjects (age: 13.8 +/- 2.2 years) matched for age, sex, body mass index, and height standard deviation score were involved in the study. Using a sine-wave transcutaneous stimulator, current perception threshold (CPT) testing at 2000, 250 and 5 Hz was performed on the left median and peroneal nerves. Diabetic children had increased CPT at 2000 Hz on both nerves as compared to the control group (median (interquartile range), median nerve: 2.43 (2.20-3.43) vs 1.80 (1.51-2.60) mA, p = 0.02; peroneal nerve: 3.51 (2.81-4.82) vs 2.70 (2.04-3.70) mA, p = 0.01). Twenty-one (23%) of patients had CPT values higher than that of any healthy individual. Of these, elevated CPT was observed in 9 (9.8%) patients on the median nerve, in 8 (8.7%) patients on the peroneal nerve, and in 4 (4.3%) patients on both median and peroneal nerves. Using multiple logistic regression analysis, worse long-term metabolic control and advanced puberty were independently predictive of peripheral sensory nerve dysfunction as the dependent variable (adjusted OR (95% CI): 3.4 (1.2-6.2), p = 0.01, and 2.8 (1.1-5.6), p = 0.03, respectively). In conclusion, evidence of peripheral sensory nerve dysfunction is not rare in children and adolescents with diabetes and can be demonstrated by CPT testing in asymptomatic patients. Poor metabolic control is a risk factor for such subclinical neuropathy, and pubertal development may be involved in the pathogenesis of diabetic peripheral neuropathy.     

Beclomethasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not

BACKGROUND: Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn. METHODS: In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20. RESULTS: The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18). CONCLUSION: Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested.     

Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia

OBJECTIVE: Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed. RESULTS: Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone dose during the final week was 45+/-17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p=0.0001) and reductions in steady pain (34+/-26 versus 55+/-27 mm, p=0.0001), allodynia (32+/-26 versus 50+/-30 mm, p=0.0004), and paroxysmal spontaneous pain (22+/-24 versus 42+/-32 mm, p=0.0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8+/-1.1 versus 0.7+/-1.0, p=0.0001; 0.3+/-0.8 versus 0.7+/-1.0, p=0.041; 67% versus 11%, p=0.001, respectively). CONCLUSIONS: Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.     

Decreased sensitivity in the membranous urethra after orthotopic ileal bladder substitute

PURPOSE: The effect of cystoprostatectomy with orthotopic substitution on membranous urethral sensation and subsequent urinary continence is unknown. We determined the sensory threshold for electrical stimulation of the membranous urethra and correlated it with continence, nerve sparing surgical technique and potency. MATERIALS AND METHODS: The sensory threshold was measured in a control group of 35 men before radical prostatectomy or cystoprostatectomy and in 47 men after cystoprostatectomy and ileal bladder substitution. RESULTS: The sensory threshold of the membranous urethra was 9+/-2 in the control group compared to 27+/-11 mA. in the postoperative group (p<0.001). Patients with daytime continence had a threshold of 24+/-9 compared to 39+/-10 mA. in incontinent patients (p<0.001). We were unable to show any correlation between the sensory threshold in patients with (25+/-10 mA.) and without (31+/-11 mA.) attempted nerve sparing surgery (p = 0.1) nor between potent (25+/-12 mA.) and impotent (27+/-11 mA.) patients (p = 0.4). CONCLUSIONS: Sensitivity in the membranous urethra decreased in patients after cystoprostatectomy and ileal bladder substitution. Urethral sensitivity in the sphincter area was better in continent than incontinent patients. Since we were unable to find any correlation between the sensory threshold and nerve sparing surgery or potency, it may be assumed that at least part of the sensory fibers to the membranous urethra pass through the pudendal nerve and/or the intrapelvic extrapudendal nerve fibers.     

Cost-effectiveness and cost-benefit analysis of using methotrexate vs Goeckerman therapy for psoriasis. A pilot study

PURPOSE: To compare topical tetracaine 0.5% alone and with intracameral lidocaine 1% as a local anesthetic agent in phacoemulsification with intraocular lens (IOL) implantation. SETTING: The Toronto Hospital-Western Division, Toronto, Canada. METHODS: Fifty-nine consecutive patients (60 eyes) having phacoemulsification with implantation of a foldable acrylic IOL (AcrySof) were randomized into 1 of 2 groups: The intracameral balanced salt solution (BSS) group received topical tetracaine 0.5% plus intracameral BSS; the intracameral lidocaine group received topical tetracaine 0.5% with preservative-free intracameral lidocaine 1%. The patients' subjective experience of pain was measured at 4 points during surgery using a 4-point pain scale. Patient and surgeon satisfaction with the anesthesia used was measured using a 5-point satisfaction scale. Central endothelial cell counts were obtained preoperatively and 1 month postoperatively. Best corrected visual acuity (BCVA) was measured preoperatively and 1 hour, 1 day, 1 week, and 1 month postoperatively. RESULTS: The mean pain score after phacoemulsification was significantly higher in the intracameral BSS group than in the intracameral lidocaine group (0.63 +/- 0.7 [SD] and 0.23 +/- 0.4, respectively, P < .019). The mean pain score at the end of surgery was also significantly higher in the intracameral BSS group than in the intracameral lidocaine group (0.60 +/- 0.6 and 0.21 +/- 0.4, respectively; P < .014). The surgeon satisfaction score was significantly lower for the intracameral BSS group than for the intracameral lidocaine group (3.90 +/- 1.2 and 4.73 +/- 0.8, respectively; P < .0007). There was no difference in patient satisfaction between the intracameral BSS and intracameral lidocaine groups (4.60 +/- 0.6 and 4.70 +/- 0.8). Endothelial cell loss 1 month postoperatively was similar between the 2 groups (6.1% +/- 8% and 6.7% +/- 6%). Ninety-seven percent of patients (29/30) in each group noted BCVA improvement from preoperatively. The rate of potential visual acuity recovery was similar in both groups. CONCLUSION: Topical tetracaine 0.5% with intracameral lidocaine was safe and effective in patients having phacoemulsification with IOL implantation. The advantage of using intracameral lidocaine 1% over a placebo was a significant decrease in the patients' subjective experience of pain and in the surgeon's satisfaction with the anesthesia used. None of the other parameters measured in this study differed significantly between the 2 groups.     

A clinical trial of escalating doses of flumazenil for reversal of suspected benzodiazepine overdose in the emergency department

STUDY OBJECTIVE: To determine if flumazenil, when used in doses higher than those currently recommended, could reverse the effects of a benzodiazepine (BDZ) overdose in patients who might not otherwise respond and whether the higher dose was associated with increased adverse effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, balanced, with parallel groups. Open-label flumazenil administration was available if a patient failed to respond or became resedated. SETTING: Sixteen emergency departments in the United States. POPULATION: Patients presenting to the ED with clinically significant signs and symptoms of a known or suspected BDZ overdose. INTERVENTIONS: Patients were randomized to receive 10 mL/min of placebo or flumazenil (1 mg/10 mL) each minute for ten minutes. If there was no response, up to 3 mg of open-label flumazenil could be administered. MEASUREMENTS AND MAIN RESULTS: Of 170 patients enrolled, 87 received flumazenil and 83 received placebo. The demographic characteristics of both groups were comparable. Ten minutes after the beginning of study drug infusion, patients were evaluated using the Clinical Global Impression Scale (CGIS), Glasgow Coma Scale (GSC), and Neurobehavioral Assessment Scale (NAS). The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil. The mean +/- SD dose of flumazenil administered during the double-blind phase was 71.3 +/- 34.2 mL (7.13 mg) compared with 95.06 +/- 16.03 mL of placebo. Of the 39 patients who had BDZ-positive drug screens and received flumazenil, 29 (74%) responded to 3 mg or less. Six additional patients responded to 4 or 5 mg, and one patient responded to 8 mg. The most common adverse effects in patients who received flumazenil were injection site pain (10.3%), agitation (8%), vomiting (3.4%), dizziness (3.4%), headache (3.4%), tachycardia (3.4%), and crying (3.4%). Three patients developed seizures. Two were associated with significant tricyclic antidepressant overdoses and one with propoxyphene ingestion. Two patients had positive drug screens for BDZ. CONCLUSION: Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose. Most patients will respond to 3 mg or less, but a small number may require a higher dose for reversal of clinical symptoms. Patients with concomitant tricyclic antidepressant overdose may be at risk for developing seizures.     

Catheter-based radiotherapy to inhibit restenosis after coronary stenting

BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy has been shown to reduce the intimal hyperplasia that is a part of restenosis. We studied the safety and efficacy of catheter-based intracoronary gamma radiation plus stenting to reduce coronary restenosis in patients with previous restenosis. METHODS: Patients with restenosis underwent coronary stenting, as required, and balloon dilation and were then randomly assigned to receive catheter-based irradiation with iridium-192 or placebo. Clinical follow-up was performed, with quantitative coronary angiographic and intravascular ultrasonographic measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were assigned to the iridium-192 group and 29 to the placebo group. Angiographic studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2 months. The mean minimal luminal diameter at follow-up was larger in the iridium-192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02). Late luminal loss was significantly lower in the iridium-192 group than in the placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically identified restenosis (stenosis of 50 percent or more of the luminal diameter at follow-up) occurred in 17 percent of the patients in the iridium-192 group, as compared with 54 percent of those in the placebo group (P= 0.01). There were no apparent complications of the treatment. CONCLUSIONS: In this preliminary, short-term study of patients with previous coronary restenosis, coronary stenting followed by catheter-based intracoronary radiotherapy substantially reduced the rate of subsequent restenosis.     

Changes in crystallinity by sterilization and processing of ultrahigh molecular polyethylene used in endoprosthetics]

Research in animals shows that the levels of neuropathic pain expression is genetically associated with a characteristic response profile to sensory stimuli. The aim of the present investigation was to examine if pressure algometry can identify a specific pain sensitivity profile in patients with complex regional pain syndrome, Type I (reflex sympathetic dystrophy), and to distinguish complex regional pain syndromes from other chronic pain dysfunction syndromes. Pressure pain threshold and pain tolerance measured at the sternum in 17 patients with complex regional pain syndrome, Type I (reflex sympathetic dystrophy), were compared with values obtained in 13 patients suffering from other chronic pain dysfunction syndromes and in a control group of 24 pain-free volunteers. The pressure algometer consisted of a force displacement transducer with a 0.25 cm2 tip connected to a recorder. The rate of force application was 1 kg/0.25 cm2/s. The difference between threshold and tolerance was defined as the pain sensitivity range. Young patients with complex regional pain syndrome (<40 yr) demonstrated a significantly higher mean pain sensitivity range compared with young subjects who had chronic pain or who were pain-free. Mean threshold and tolerance values were significantly lower in patients with complex regional pain syndrome (2.7+/-1.0 kg (mean +/- standard deviation) and 5.4+/-2.0 kg, respectively) and in patients suffering from other chronic pain syndromes (2.6+/-1.1 and 4.6+/-1.7 kg) than in healthy subjects (5.4+/-2.3 and 8.4+/-2.6 kg). Women in the chronic pain group exhibited a significantly lower pressure pain threshold than all other subgroups. Regardless of group, women exhibited lower pressure pain tolerance than men. In conclusion, the study contained herein shows a specific pain sensitivity profile to experimental stimuli behavior in young patients with complex regional pain syndrome expressed by a large pressure pain sensitivity range, at a location away from the painful area. However, one single pressure pain measurement over the sternum is insufficient for differentiation of patients with complex regional pain syndrome from those with chronic pain because of intersubject variation.     

Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery

BACKGROUND: Atrial fibrillation occurs commonly after open-heart surgery and may delay hospital discharge. The purpose of this study was to assess the use of preoperative amiodarone as prophylaxis against atrial fibrillation after cardiac surgery. METHODS: In this double-blind, randomized study, 124 patients were given either oral amiodarone (64 patients) or placebo (60 patients) for a minimum of seven days before elective cardiac surgery. Therapy consisted of 600 mg of amiodarone per day for seven days, then 200 mg per day until the day of discharge from the hospital. The mean (+/-SD) preoperative total dose of amiodarone was 4.8+/-0.96 g over a period of 13+/-7 days. RESULTS: Postoperative atrial fibrillation occurred in 16 of the 64 patients in the amiodarone group (25 percent) and 32 of the 60 patients in the placebo group (53 percent) (P=0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than were patients in the placebo group (6.5+/-2.6 vs. 7.9+/-4.3 days, P=0.04). Nonfatal postoperative complications occurred in eight amiodarone-treated patients (12 percent) and in six patients receiving placebo (10 percent, P=0.78). Fatal postoperative complications occurred in three patients who received amiodarone (5 percent) and in two who received placebo (3 percent, P= 1.00). Total hospitalization costs were significantly less for the amiodarone group than for the placebo group ($18,375+/-$13,863 vs. $26,491+/-$23,837, P=0.03). CONCLUSIONS: Preoperative oral amiodarone in patients undergoing complex cardiac surgery is well tolerated and significantly reduces the incidence of postoperative atrial fibrillation and the duration and cost of hospitalization.     

Anorectal sensitivity in patients with obstructed defaecation

Patients with obstructed defaecation (OD) perform major defaecatory efforts that lead progressively to pudendal motor neuropathy. Anorectal sensory function in these patients and its possible influence in the pathogenesis of the disease have been little studied. In the present paper we investigated anorectal sensitivity to electric and thermal stimuli in patients with OD, and studied the possible existence of pudendal sensory neuropathy associated to their known pudendal motor neuropathy. Forty subjects were divided into two groups: 21 healthy controls (11 females and 10 males; mean age 51.8 +/- 11 years, range 33-67) and 19 patients with OD (18 females and 1 male; mean age 48 +/- 15 years, range 20-71). The patients with OD suffered constipation and an obstruction sensation upon defaecating, even in the case of soft stools. Clinical perineometry, manometry, pudendal motor latency studies, external anal sphincter single fibre electromyography and the evaluation of sensitivity to electric and thermal stimuli were carried out in all cases. All pudendal motor function parameters showed statistically significant differences between the two groups. In the controls the electrical sensitivity threshold was minimal in the mid anal canal, where sensory receptor presence is greater. Sensitivity was significantly higher in the upper and lower anal canal regions (P < 0.05), and much higher in the rectum (P < 0.001). A similar sensory profile was recorded in the patients with OD, though with significantly higher thresholds at all points with respect to the controls. The thermal stimulus thresholds in the lower and middle anal canal were significantly smaller than in the upper canal region and rectum, and the thresholds were again higher among the patients with OD than among the controls. In all cases the thresholds for heat were lower than for cold stimuli. In both groups the motor function parameters were correlated with the sensory function variables, and the latter between themselves. Patients with OD presented sensory deterioration at all points studied in the anal canal and rectum. Sensory pudendal neuropathy was found to be associated with the pudental motor neuropathy.     

Sedation with midazolam during regional anaesthesia: is there a role for flumazenil?

The aim of this study was to reassess the efficacy of flumazenil for reversal of sedation with midazolam. Twenty-four ASA I or II patients undergoing elective surgery under epidural anaesthesia participated. Following epidural block, midazolam was administered to keep the patient sleepy but still responsive to verbal commands. At the end of surgery the patients were randomly allocated to receive, in a double-blind manner, either flumazenil (0.1 mg.ml-1) or placebo. The study drug (maximum dose: 10 ml) was titrated until the patient became fully awake. Sedation was assessed with the Modified Steward Coma Scale (MSCS), the Trieger test (TT) and Critical Flicker Frequency (CFF). The assessments were done before anaesthesia (baseline), at the end of surgery immediately before administration of study drug, and serially afterwards, at 10, 30, 60, 90, 120, 150 and 180 min. Analyses of variance for repeated measures and pooled t tests were used. The duration of surgery was (mean +/- SD) 0.72 +/- 0.25 hr in the flumazenil group and 0.74 +/- 0.28 hr in the placebo group. The total dose of midazolam was 7.2 +/- 2.2 mg for the flumazenil group and 8.9 +/- 2.7 mg for the placebo group. The volume of study drug administered was 5.5 ml +/- 1.9, equivalent to 0.55 mg, for the flumazenil group and 6.7 +/- 2.2 ml for the placebo group. Critical Flicker Frequency is the only measure which revealed a difference (P < 0.005) between the flumazenil and placebo groups and this occurred only at the ten-minute assessment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrathecal fentanyl prolongs sensory bupivacaine spinal block

The purpose of investigation was to study the effect of intrathecal fentanyl on the onset and duration of hyperbaric bupivacaine-induced spinal block in adult male patients. Forty-three patients undergoing lower extremity or genitourinary surgery were enrolled to receive either 13.5 mg hyperbaric bupivacaine 0.75% + 0.5 ml CSF it, (Group I) or 13.5 mg hyperbaric bupivacaine 0.75% + 25 micrograms fentanyl it, (Group II) according to a randomized assessor-blind protocol. The onset and duration of sensory block were assessed by pinching the skin with forceps in the midclavicular line bilaterally every two minutes for first twenty minutes and then every five to ten minutes. Similarly, the onset and duration of motor block were assessed and graded at the same time intervals using the criteria described by Bromage. The time required for two sensory segment regression and sensory regression to L1 dermatome was 74 +/- 18 and 110 +/- 33 min vs 93 +/- 22 and 141 +/- 37 min in Groups I and II, respectively (P < 0.05). Intrathecal fentanyl did not enhance the onset of sensory or motor block, or prolong the duration of bupivacaine-induced motor spinal block. Fewer patients demanded pain relief in the fentanyl-treated group than in the control group in the early postoperative period (19% vs 59%; P < 0.05). Episodes of hypotension were more frequent in the fentanyl-treated group than in the control group (43% vs 14%; P < 0.05). We conclude that fentanyl, 25 micrograms it, prolonged the duration of bupivacaine-induced sensory block (sensory regression to L1 dermatone) by 28% and reduced the analgesic requirement in the early postoperative period following bupivacaine spinal block.