GM-CSF IMPROVES GAS EXCHANGE IN SEPSIS

A low-dose infusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) may improve oxygenation in patients with sepsis-related pulmonary dysfunction, a phase II study by Presneill et al suggests.

The randomized, double-blind, controlled trial included 18 traditional intensive care management, patients received either five consecutive daily infusions of GM-CSF (3 µg/kg of body weight) or placebo. The primary outcome was patient survival at 30 days. Before the first and after the fifth dose, cells were collected from peripheral blood and bronchoalveolar lavage.

There was no between-group difference in survival after 30 days. The addition of GM-CSF resulted in a marked improvement in oxygenation over five days, compared with no change in the placebo group. This improvement persisted for five days after therapy was discontinued.

The incidence of acute respiratory distress syndrome, which was similar at baseline in the two groups, increased in the placebo group but decreased in those given GM-CSF. Therefore, the authors suggest that GM-CSF may enhance leukocyte function without worsening pulmonary or other organ dysfunction.

An editorial commentary by Trapnell suggested that the lack of improvement in mortality may have been due to the small number of patients, the lack of controls for glucocorticoid use, and the fact that patients were not stratified by their degree of monocyte deactivation at the time of enrollment. Trapnell suggested the need for dose optimization based on immunophenotyping.

Presneill JJ, Harris T, Stewart AG, et al. A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction. Am J Respir Crit Care Med. 2002;166:138-143.
Trapnell BC. Granulocyte macrophage–colony stimulating factor augmentation therapy in sepsis: is there a role? Am J Respir Crit Care Med. 2002;166:129-130.

CANDIDEMIC SEPTIC SHOCK RARE BUT DEADLY

Although rare in nonimmunocompromised patients, candidemia accompanied by septic shock has a high rate of organ failure and death, reported Hadley et al after conducting a cohort analysis of data from the North American Septic Shock Trial.

The trial analyzed data for 386 patients with septic shock (376 bacteremic and 10 candidemic) to compare differences in the course of illness and 28-day mortality. All patients received standard medical care or surgical therapy as needed.

Immunocompromise was uncommon among the patients in this study; for example, only 46 (12%) had cancer or were HIV-positive. Candida albicans was the predominant cause of septic shock in the patients with candidemia.

During the study, both renal failure and hepatic failure were more common in the patients with candidemia than in those with bacteremia. In addition, the candidemic patients were more likely to develop multiple organ failure during the course of the study, to have a greater number of organs affected, and to die as a result. However, possibly because of the small number of patients with candidemia, only the difference in the rate of hepatic failure was statistically significant.

The authors recommended the continued study of empirical antifungal therapy for patients at risk.

Hadley S, Lee WW, Ruthazer R, Nasraway SA Jr. Candidemia as a cause of septic shock and multiple organ failure in nonimmunocompromised patients. Crit Care Med. 2002;30:1808-1814.

RAPID STREP TEST SENSITIVE AND SPECIFIC

The rapid strep test has a high level of sensitivity and specificity in diagnosing streptococcal pharyngitis, even among patients who have recently had a strep infection.

A study by Sheeler et al compared the rapid test for streptococcal antigens with the two-step culture method. Two hundred eleven patients with sore throat, all of whom had been treated for streptococcal infection during the past 28 days (cases), were compared with 232 patients complaining of sore throat who had not recently been diagnosed with a strep infection (controls).

During the study, all specimens were screened using the rapid strep test and by the definitive culture method, which involves incubating cultures for 48 hours. All positive cultures were tested for Streptococcus pyogenes using a direct fluorescent antibody test.

The rapid strep test had 96% specificity in the case patients, compared with 98% in the control group. The rapid strep test had higher sensitivity in the case patients (91%) than in controls (70%). The amount of time elapsed since the last antibiotic treatment did not influence specificity or sensitivity. The authors note that using the rapid strep test can save time and facilitate earlier treatment of patients and resolution of symptoms.

Sheeler RD, Houston MS, Radke S, et al. Accuracy of rapid strep testing in patients who have had recent streptococcal pharyngitis. J Am Board Fam Pract. 2002;15:261-265.

VACCINES DON’T INCREASE ASTHMA RISK

There is no apparent association between childhood immunizations and risk of developing asthma, according to a recent cohort study by Destefano et al.

The investigators analyzed information from the Vaccine Safety Datalink project, which linked the automated clinical databases of four health maintenance organizations. The study followed 167,240 children from birth until at least 18 months to a maximum of 6 years. A total of 18,407 children were diagnosed with asthma. The median age at last follow-up was 28 months, and median age at asthma onset was 11 months.

Diphtheria, tetanus, and whole-cell pertussis; oral polio (OP); and measles, mumps, and rubella vaccines were not associated with an increased risk of developing asthma. However, the relative risk of asthma was slightly elevated for the Haemophilus influenzae type b (Hib) and hepatitis B vaccines (Table 1). Among the children who had had at least two medical care encounters during their first year of life, no increased risk of asthma was seen with the Hib or hepatitis B vaccines.

The authors note that the increased relative risks for the Hib and hepatitis B vaccines were unexplained and probably the result of medical care utilization bias or random chance.

Destefano F, Gu D, Kramarz P, et al. Childhood vaccinations and risk of asthma. Pediatr Infect Dis J. 2002;21:498-504.

STUDY RAISES QUESTIONS ABOUT BRONCHODILATOR

According to a report by Anthonisen et al, the Lung Health Study has shown that smoking cessation significantly reduces the incidence of fatal or nonfatal cardiovascular disease and coronary artery disease—but not lung cancer—after five years. The study also found suggestive, but inconclusive, evidence that ipratropium bromide may increase the risk of cardiovascular events.

The study randomized 5,887 smokers to receive either smoking intervention plus inhaled ipratropium (two puffs three times per day), smoking intervention plus placebo inhaler, or usual care. All participants underwent annual visits that included questionnaires on smoking, use of prescription drugs, serious illness, hospitalization, and physician visits. The two intervention groups were offered a 10-week smoking cessation program, with visits every four months to encourage compliance. Smoking status was verified biochemically; inhaler compliance was ascertained by patients’ self report.

After five years, more than 21% of both intervention groups had quit smoking, compared to 5.4% of the usual care group. In comparison to cessation, continued smoking was found to increase the risk of fatal or nonfatal cardiovascular events by 50%.

Surprisingly, deaths from and hospitalizations for cardiovascular disease were more common in the ipratropium group than in the placebo group, a difference that approached significance. Although the authors were unable to definitively attribute this to ipratropium use because no dose-response relationship could be seen, they identified nine patients with supraventricular tachycardia in the ipratropium group, six of whom were described as having “unusually good” compliance with therapy. The authors also noted that supraventricular tachycardia is a credible side effect of ipratropium.

Anthonisen NR, Connett JE, Enright PL, et al. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med. 2002;166:333-339.

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