PROTEIN C DYSFUNCTION IN MENINGOCOCCAL SEPSIS

Thrombosis associated with sepsis is related to inhibition of the protein C anticoagulation pathway, as is the development of purpura fulminans in meningococcemia, according to a new study. Faust et al found that expression of endothelial thrombomodulin and of endothelial protein C receptor was lower in patients with meningococcal sepsis than in controls—both in blood vessels with and in vessels without thrombosis.

The researchers examined 21 biopsy specimens of purpuric lesions from children with meningococcal sepsis. These were compared with skin-biopsy specimens from five children without sepsis. Electron microscopy showed that in the children with sepsis, endothelial cells were intact in both thrombosed and non-thrombosed vessels; however, these cells were less able to express thrombomodulin than were the control endothelial cells. Nevertheless, median plasma thrombomodulin levels were 6.4 ng/L in the children with meningococcal sepsis compared with 3.6 ng/L in controls. Conversely, plasma levels of protein C antigen, protein S antigen, and antithrombin antigen were lower in the children with sepsis than in the controls.

The speculative conclusion the researchers drew was that the association between purpura fulminans and meningococcal sepsis is explained by the more profound dysfunction of the endothelial protein C pathway in this disease than in other forms of sepsis.

Faust S, Levin M, Harrison O, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med. 2001;345:408-416.

LOW VT EFFICACY DOES NOT CHANGE WITH RISK FACTORS

Low tidal volume (VT) ventilation—when compared with traditional forms of mechanical ventilation—has been shown to reduce mortality by 22% in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Eisner et al found that the efficacy of a tidal volume of 6 mL/kg does not appear to be affected by clinical risk factors for ALI/ARDS.

The researchers evaluated the relative efficacy of low VT ventilation in 902 patients, all of whom had been drawn from ARDS Network randomized controlled trials and had different risk factors for ALI/ARDS. Of these, 473 had been treated with a low VT strategy; the other 429 patients had been given traditional ventilation.

The researchers found that clinical risk factors had a profound influence on the risk of death before discharge home; for example, this risk was 43% for patients with sepsis, 36% for patients with pneumonia, 37% for patients experiencing aspiration, and 11% for those with trauma. However, there was no evidence that the efficacy of low VT ventilation varied in any of these subgroups.

Nor was there any evidence of a difference in the efficacy of low VT ventilation among subgroups when the authors examined other study outcomes, such as the proportion of patients achieving unassisted breathing, the number of ventilator-free days, or the development of non-pulmonary organ failure.

Furthermore, reclassification of predisposing clinical risk factors as pulmonary versus non-pulmonary, or as infection-related versus non–infection-related had no appreciable effect on the results. Neither did controlling for demographic and clinical covariates. This, the researchers concluded, provides ample evidence for the implementation of low VT strategies in patients with ALI/ARDS.

Eisner MD, Thompson T, Hudson LD. Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;164:231-236.

S AUREUS OFTEN INFECTS CARDIAC DEVICES

Cardiac device infections caused by Staphylococcus aureus bacteremia (SAB) are surprisingly common, a recent study has demonstrated. Chamis and coworkers have also found that physical examination and echocardiography cannot be relied upon to rule out cardiac device infections.

Thirty-three patients with SAB and implanted cardiac devices were evaluated prospectively for a six-year period. SAB was considered to be clinically significant when more than one blood culture was positive for S aureus or if a single blood culture showed S aureus in a patient with clinical signs of infection.

The SAB cases were defined as early if they occurred less than one year after device implantation or its last alteration, or late if they occurred more than one year after those procedures. The total incidence of cardiac device infections was 45.4%; no specific type of device appeared to be more commonly associated with infection. Confirmed cases of infection occurred more commonly in patients with early SAB than in those with late SAB (75% vs 28.5%, respectively).

The incidence of cardiac device infections hematogenously seeded from a distant or unknown primary infection site was 27.3%. Local signs of generator pocket infection were absent in 60% (9 of 15) of the patients with confirmed cardiac device infections, but generator pocket cultures found S aureus in five of these instances.

The researchers said that SAB posed great risks for patients with permanent pacemakers or implantable cardioverter-defibrillators, and that it should be suspected in all patients with SAB during the first year after implantation. They added that further studies were needed to identify other clinical characteristics that could be used to determine which bacteremic patients had infected cardiac devices.

Chamis AL, Peterson GE, Cabell CH, et al. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation. 2001;104:1029-1033.

VASOPRESSIN VERSUS EPINEPHRINE FOR CARDIAC ARREST

A triple-blind, randomized trial has compared the efficacy of vasopressin and epinephrine for in-hospital cardiac arrest. Steill et al found no advantage in using vasopressin as the initial vasopressor.

The researchers assigned patients experiencing cardiac arrest in three teaching hospitals to intravenous vasopressin (40 U) or epinephrine (1 mg). Primary outcomes observed for the 104 patients receiving vasopressin and the 96 receiving epinephrine were survival to 1 h, survival to hospital discharge, and neurological function.

Epinephrine was used as a rescue medication for those patients who did not respond to the first dose of vasopressin or epinephrine. All patients were treated in accordance with the standard Advanced Cardiac Life Support (ACLS) protocols; the medications were administered at the point in those protocols at which epinephrine was initially indicated.

Rates of survival to 1 h and to hospital discharge differed only slightly between the two groups. In the patients given vasopressin, those rates were 39% and 12%, respectively; in the patients receiving epinephrine, they were 35% and 14%, respectively. Similarly, the median Mini-Mental State Examination scores were 36 in the vasopressin group and 35 in the epinephrine group.

The researchers stated clearly that they failed to find the slightest trend favoring vasopressin in subgroups with myocardial ischemia or infarction, or with ventricular fibrillation or tachycardia. Because of this, they clearly stated their opposition to the American Heart Association’s recommendation in the ACLS guidelines that vasopressin be used as an alternative therapy for cardiac arrest, unless further clinical trials should provide evidence that it really can improve survival to hospital discharge.

Steill I, Hèbert P, Wells G, et al. Vasopressin versus epinephrine for in-hospital cardiac arrest: a randomised controlled trial. Lancet. 2001;358:105-109.

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