Management of fibromyalgia, a distinct rheumatologic syndrome.

The pathophysiology and management of fibromyalgia, a unique nonarticular rheumatologic syndrome characterized by diffuse musculoskeletal aches and pains, stiffness, discrete tender points at typical soft-tissue sites, and a characteristic sleep disturbance, are reviewed. The prevalence and incidence of fibromyalgia are not known, but it is one of the most common conditions seen by rheumatologists (after degenerative joint disease and rheumatoid arthritis). It was previously thought to involve inflammation of fibrous intermuscular septa and is sometimes referred to in the literature as fibrositis. It is not primarily psychogenic, but psychological factors may contribute. The tender points are the key to diagnosis. Fibromyalgia may be classed as primary (when no underlying disease is present) or secondary (when an associated condition exists). The pathophysiology of fibromyalgia is unknown but appears to involve complex interactions of central neurotransmitters with a relationship to pain perception, mood, and sleep. Treatment is empiric; nondrug treatment involving education, relaxation, and increased physical activity is essential. Few controlled trials of drug therapy have been conducted. Analgesics, anti-inflammatory drugs, phenothiazines, tricyclic antidepressants, and the tricyclic muscle relaxant cyclobenzaprine have been used; low doses of amitriptyline or cyclobenzaprine provide increased control of pain and mood.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin kinetics: variables related to disposition and dosage.

A method to determine heparin kinetics and dosage requirements was examined in 20 patients with active thromboembolic disease. Pretreatment heparin sensitivities were determined to establish the relationship between heparin concentration and activated partial thromboplastin times (APTTs). After an initial bolus dose, serial APTTs were measured, heparin concentrations were estimated, and kinetic determinations followed. Heparin elimination rate, distribution volume, and clearance were used to calculate dosage requirements. There was a 500% range in pretreatment heparin sensitivities. Smokers had more rapid heparin elimination rates and t 1/2s than nonsmokers did. Men had more rapid drug clearances than women did. Body weight was related to heparin dosage requirements. Patients treated early after onset of symptoms required higher doses than patients in whom treatment was delayed. A multiple regression model was developed for heparin dosage requirements from body weight, sex, delay between onset of symptoms and treatment, and smoking. This statistical model explained 78% of the variance in heparin requirements.

Effect of cardiopulmonary bypass on cefazolin disposition.

Cefazolin kinetics was studied in 8 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass (CPB) surgery. PREOP (48.6 ml/min) and POSTOP (46.6 ml/min) total body clearances were of the same order and both were greater than the SURG (27.4 ml/min) total body clearance. Since cefazolin is almost entirely eliminated by the kidney, the lower SURG clearance is a result of reduced renal elimination, as confirmed by measuring cefazolin SURG (28.7 ml/min) and POSTOP (52.9 ml/min) renal clearance. The reduction in cefazolin renal elimination was the same throughout the surgical procedure, including the period of extracorporeal circulation. Cefazolin distribution was altered by the operative procedure as evidence by a higher SURG steady-state volume of distribution. This increase in apparent cefazolin distribution volume brought about by surgery was not seen with cephalothin, which was investigated by us in a similar group of patients. The different effect of CPB surgery on cefazolin and cephalothin distribution may be due to differences in plasma protein binding.