SHORTER DURATION OF TREATMENT FOR ACETAMINOPHEN OVERDOSE

A short course of oral acetylcysteine therapy appears to be safe and effective for patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose, according to the results of a recent retrospective study conducted by Woo et al.

Acetylcysteine enhances detoxification of the reactive metabolite of acetaminophen; however, in most cases, the parent compound of this drug is eliminated completely within 10 to 20 hours, and further production of the reactive metabolite is unlikely. Based on this information, Woo et al hypothesized that treatment with acetylcysteine is probably not needed after 20 hours.

The researchers reviewed the medical records of 75 patients with possible or probable toxicity following an acute overdose of acetaminophen. A third of the group had been treated with acetylcysteine for less than 24 hours, a third for 24 to 36 hours, and a third for 37 to 64 hours. In all patients, therapy had been initiated within 24 hours of acetaminophen ingestion.

The incidence of hepatotoxicity (ie, aminotransferase levels above 1,000 IU/L) is shown in Table 1. None of the patients died or required liver transplantation.

"Our experience and that of others suggests that evidence of impending hepatotoxicity is apparent within 30 to 36 hours after an acute ingestion," according to the researchers. Because of these data, they believe that patients without such evidence within 36 hours can be safely treated with acetylcysteine for 24 hours or less.

Woo O, Mueller PD, Olson KR, et al. Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Ann Emerg Med. 2000;35:363-368.

INVASIVE MANAGEMENT STRATEGY FOR VENTILATOR-ASSOCIATED PNEUMONIA

When ventilator-associated pneumonia is suspected, which approach works best for establishing the diagnosis and managing the patient? A new study suggests an invasive strategy that includes fiberoptic bronchoscopy improves survival and lowers the rates of organ failure and antibiotic use.

Fagon et al randomized 413 patients to an invasive or noninvasive management strategy. In the former group, results of fiberoptic bronchoscopy were used to diagnose ventilator-associated pneumonia, to decide whether to treat the patient, and to guide the initial choice of antibiotics for patients with positive specimens. In the latter group, the decision to treat the patient was based on clinical evaluation and the results of microscopic examination of Gram-stained endotracheal aspirates. Patients were followed for four weeks after randomization.

Compared with the noninvasive group, the invasive group had a significantly lower mortality rate (16.2% vs 25.8%) and a significantly higher number of antibiotic-free days (5.0 vs 2.2) by day 14. The Sepsis-related Organ Failure Assessment score was also significantly lower in the invasive group than in the noninvasive group on days 3 and 7, but not on day 14.

The decreased mortality rate in the invasive group persisted throughout the study but was no longer significant by day 28. Nonetheless, there were 18 fewer deaths in the invasive group than in the noninvasive group at that point. In addition, by the end of the study, the invasive group had had significantly more antibiotic-free days and had required fewer antibiotics per day than did the noninvasive group.

Fagon et al offered the following possible explanations for the lower mortality rate in the invasive group:

• The antibiotics initially prescribed in the invasive group were more often appropriate.
• The invasive strategy prevents antibiotic overuse, which can lead to development of resistant organisms and delay the diagnosis of the true cause of fever and pulmonary infiltrates.
• Negative bronchoscopy specimens will direct attention away from the lungs as a source of fever and may lead to early treatment of the true site of infection.

Fagon JY, Chastre J, Wolff M, et al. Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial. Ann Intern Med. 2000;132:621-630.

CATHETER-ASSOCIATED URINARY TRACT INFECTIONS ARE USUALLY ASYMPTOMATIC

Most cases of catheter-associated urinary tract infection (UTIs) are asymptomatic, according to data from a prospective trial. Furthermore, those symptoms that are associated with catheter-associated UTIs are of little value in the diagnosis of these infections.

Tambyah and Maki evaluated 1,497 newly catheterized patients for signs and symptoms commonly associated with UTIs (fever, dysuria, urgency, or flank pain). For all patients, qualitative urine cultures and urine leukocyte counts were also performed.

The researchers identified 235 UTIs in 224 patients, 92.3% of whom were asymptomatic. Interestingly, the patients' physicians had diagnosed only 52% of the 235 infections. Only one of the catheter-associated UTIs was unequivocally associated with a secondary bloodstream infection.

Because many of the patients in the original cohort had another active infection unrelated to the urinary tract, the researchers also examined a subset of 1,034 patients with either no infection (n = 945) or catheter-associated UTIs (n = 89). These two groups were similar in regard to UTI signs and symptoms as well as mean peripheral leukocyte counts. The only significant difference between the two groups was a higher mean urine white blood cell count in the catheter-associated UTI group.

According to the researchers, asymptomatic UTIs "comprise a huge silent reservoir of antibiotic-resistant bacteria and yeasts." Thus, they recommend improved catheter care to prevent such infections.

Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Arch Intern Med. 2000;160:678-682.

REDUCING BACTERIAL RESISTENCE IN NEONATES

Elimination of amoxicillin and cefotaxime from empiric antibiotic regimens for suspected septicemia in neonates may limit the emergence of resistant gram-negative bacteria. Furthermore, a change to narrow-spectrum antibiotics in this setting does not appear to adversely affect outcome.

De Man et al compared two groups:

• 218 neonates treated with a penicillin-tobramycin regimen for early-onset septicemia and floxacillin and tobramycin for late-onset septicemia.
• 218 neonates treated with intravenous amoxicillin and cefotaxime. (This regimen has been associated with the emergence of resistant gram-negative bacilli.)

However, there was no significant difference between the two groups in terms of mortality or proportion of days on the ventilator. And the number of ICU days was actually lower in the neonates who received narrow-spectrum antibiotics.

"This study provides solid evidence of a reduction of bacterial resistance mediated by the use of antibiotics that exert little selective pressure on the mucosal environment, confirming the benefits of the often preached but less frequently practiced use of narrow-spectrum antibiotics," de Man et al noted. They added that no further problems with resistance or treatment failures have occurred at their institution after two years of using the penicillin/floxacillin-tobramycin regimen.

de Man P, Verhoeven BAN, Verbrugh HA, et al. An antibiotic policy to prevent emergence of resistant bacilli. Lancet. 2000;355:973-978.

NEUROLOGIC COMPLICATIONS IN HEPARIN-INDUCED THROMBOCYTOPENIA

Neurologic complications are relatively rare in patients with immune-mediated heparin-induced thrombocytopenia but are associated with a high comorbidity and mortality, according to findings from a retrospective analysis. The study also showed that such neurologic complications may occur in patients with a normal platelet count.

Pohl et al examined data from 120 consecutive patients who developed immune-mediated heparin-induced thrombocytopenia during an 11-year period. Eleven of the patients (9%) developed neurologic complications. These complications included ischemic cerebrovascular events in seven patients, cerebral venous thrombosis in three patients, and a transient confusional state in one patient. None of the patients experienced a primary intracerebral hemorrhage, but hemorrhagic transformation of cerebral infarctions occurred following cerebral venous thrombosis in two patients and following ischemic stroke in one patient.

The patients with neurologic complications had a significantly higher mortality rate than the rest of the patients with heparin-induced thrombocytopenia (55% vs 11%). Three patients had normal platelet counts at the time they developed neurologic complications.

Pohl C, Harbrecht U, Greinacher A, et al. Neurologic complications in immune-mediated heparin-induced thrombocytopenia. Neurology. 2000;54:1240-1245.

ALI-ARDS DIAGNOSIS: TOO MUCH IN THE EYE OF THE BEHOLDER?

The diagnosis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) often depends upon whether a chest film corresponds to criteria established by the American-European Consensus Conference (AECC). But interobserver variability in interpreting chest films can lead to widely variable diagnoses, a recent study suggests.

To test the accuracy and reliability of the ALI-ARDS consensus radiographic definition, Rubenfeld et al asked 21 physicians to interpret 28 chest films using the AECC criteria. The physicians were told only that each chest film came from an intubated patient with arterial hypoxemia. No additional clinical information or patient history was provided. The physicians were recruited from experts attending the 1997 Toronto Mechanical Ventilation Workshop and from members of the National Institutes of Health ARDS Network.

Rubenfeld et al found only moderate interobserver agreement in applying the AECC definition for ALI-ARDS. In 13 cases (43%), 20 of the 21 physicians agreed on a diagnosis. However, in nine cases (32%), five or more physicians had differing interpretations. Furthermore, among individual physicians, the percentage of radiographs interpreted as consistent with a definition of ALI-ARDS ranged from 36% to 71%.

Among the factors identified as contributing to the high variability of radiographic interpretations were mild infiltrates, pleural effusions, atelectasis, isolated lower lobe involvement, radiographic technique, and overlying monitoring equipment.

Rubenfeld et al suggested that if "the variability in radiographic interpretation causes variability in the clinical diagnosis of ALI-ARDS, this finding may account for some of the geographic and institutional variation in the incidence, risk factors, resource use, and outcomes for ALI-ARDS." To reduce interobserver variability in diagnosis, they recommended:

• Developing annotated instructional radiographs that would show mild infiltrates, pleural effusions, atelectasis, isolated lower lobe involvement, and other factors identified as contributing to high variability in radiographic interpretations.
• Modifying the current radiographic definition, or replacing it with a definition that would specify radiographic findings that are inconsistent with the presence of ALI-ARDS.

Rubenfeld GD, Caldwell E, Granton J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest. 1999;116:1347-1353.

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