Gout Clinical Update, July 13, 2011

Colchicine is commonly used for the treatment of gout and occasionally for other inflammatory diseases. But colchicine toxicity was frequent in a small cohort of hospitalized patients and may have contributed to several deaths, according to a recent study.

“Thirty-seven hospitalized patients who died during the 86-month study period received colchicine. Toxicity was unlikely in 20/37, possible in 8/37, likely in 5/37, and certain in 4/37,” according to the study, which was published in Clinical Toxicology. The study authors practice in the division of emergency medicine at Washington University in St. Louis.

“A contributing role for colchicine in causing death was unlikely in 24/37, possible in 7/37, likely in 3/37, and certain in 3/37. Colchicine doses (based on creatinine clearance) exceeded the accepted range for 12 patients, including 10 of 17 cases of toxicity and eight of 13 cases of death classified as possible or higher. Seventeen patients received interacting medications, including eight of 17 cases of toxicity and eight of 13 cases of death classified as possible or higher.”

The goal of the study was to determine the frequency of colchicine toxicity among hospitalized patients taking colchicine who died during an admission, the likelihood that colchicine contributed to death, whether patients were taking interacting medications that could have contributed to toxicity, and whether colchicine dosing among these patients adhered to established guidelines.

The researchers conducted a retrospective chart review approved by an institutional review board at an urban, tertiary care, 1228-bed, university hospital. Subjects included hospitalized patients who received colchicine and died in hospital between January 1, 2000, and February 28, 2007.

“An expert panel reviewed each case and classified the likelihood of colchicine toxicity, the likelihood of a causal role of colchicine in the death using the WHO [World Health Organization] classification system, and the appropriateness of colchicine dosing,” the authors wrote.

Gout and Oxidative Distress

Gout patients have a high incidence of atherosclerotic coronary heart disease. Low serum paraoxonase (PON) activity is considered a risk factor for atherosclerosis, but the relationships among paraoxonase-1 (PON1) activity, oxidative stress parameters, and atherosclerosis in gout is not known.

But recent research has concluded that gout patients in a study were in a state of oxidative stress and the protective effects of high density lipoprotein against atherosclerosis were perhaps dependent on PON1 activity. These findings may explain in part the reported increase in cardiovascular mortality in gout patients.

The study, which was published in Cell Chemistry and Biophysics, was conducted by researchers in the department of medical laboratory science at the Affiliated Hospital of North Sichuan Medical College in China. The researches determined the plasma levels of malondialdehyde (MDA), oxidized low-density lipoprotein (Ox-LDL), and activities of PON1/superoxide dismutase (SOD) activities in 49 gout patients (mean age 44.2 ± 7.0 years) and 42 healthy, age-matched controls (mean age 45.0 ± 9.3 years).

PON1 was measured and lipid and other biochemical parameters were determined by routine laboratory methods. PON1/SOD activities and MDA/Ox-LDL levels were 131.3 ± 25.3/75.3 ± 28.9 kU l(-1) and 6.12 ± 1.67 nmol ml(-1)/690.1 ± 180.2 μg l(-1), respectively, in gout patients. In controls, these were 172.5 ± 27.8/94.0 ± 26.3 kU l(-1) and 4.10 ± 1.25 nmol ml(-1)/452.3 ± 152.1 μg l(-1), respectively.

“Thus, in gout patients, there was a significant decrease in PON1 (P < 0.01) and SOD (P < 0.05) activities, and an increase in MDA (P < 0.01) and Ox-LDL (P < 0.01) levels compared with controls. PON1 activity correlated positively with SOD (P < 0.05), and negatively with MDA (P < 0.01) and Ox-LDL (P < 0.01),” the researchers wrote.

SourcesUnrecognized Fatalities Related to Colchicine in Hospitalized Patients [Clinical Toxicology]

Gout and Oxidative Distress [Cell Chemistry and Biophysics]