A nested-case control study was performed within a large, randomized-controlled study of initial treatment of pulmonary embolism. Patients with recurrent VTE within three months were each matched to three controls. BNP levels were drawn at baseline, and both hypertension and congestive heart failure were evaluated as potential confounders.
Cases had significantly higher baseline BNP values than controls (2.45 pmol/L versus 0.80 pmol/L). The odds ratio for each unit increase in the (log) BNP was 2.4 (95% CI: 1.5-3.7). Hypertension was not a confounding factor, but patients with a history of congestive heart failure had no association between elevated BNP and recurrent VTE. Using receiver-operating characteristic analysis, the optimal BNP cut-off of 1.25 pmol/L resulted in a sensitivity and specificity for recurrent VTE of 60% and 62%, respectively.
Three recent studies have suggested that BNP can be used to predict adverse outcomes in patients with pulmonary embolism, including mortality and eventual need for mechanical ventilation, cardiopulmonary resuscitation or thrombolysis. In this study, which included only hemodynamically stable patients with acute pulmonary embolism, however, BNP did not independently predict adverse outcomes. Nonetheless, BNP may be a useful adjunct to other clinical data in deciding whether or not to initiate thrombolytic therapy in pulmonary embolism patients without a history of congestive heart failure.—CR
Insulin Therapy in the ICU
Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006 Feb 2;354(5):449-461.
A landmark 2001 study by Van den Berghe, et al. compared tight versus liberal control of blood sugars in surgical ICU patients. The authors found that patients randomized to intensive insulin therapy had decreased mortality during intensive care compared to those receiving conventional treatment (ARR 3.4%, NNT 29).
In this follow-up study, Van den Berghe, et al., shifted the focus toward medical ICU patients. As their previous results were most dramatic in patients who stayed in the ICU for at least five days, they recruited patients expected to require at least three ICU days.
Twelve hundred patients were randomized to receive either conventional (goal BG 180-200 mg/dl) or intensive (goal BG 80-110 mg/dl) insulin treatment. The primary end point was all-cause mortality in the hospital. Secondary outcomes were also defined, including ICU mortality, 90-day mortality, days to weaning from mechanical ventilation, days in the ICU and in the hospital, renal failure, and incidence of bacteremia.
In the intention-to-treat analysis, there was no statistically significant difference in the primary end point of in-hospital mortality. Predefined subgroup analysis of patients who stayed in the ICU longer than three days showed a significant mortality benefit for the intensive insulin regimen (ARR 6.8%, NNT 15). However, in the subgroup of patients staying less than three days in the ICU, there was increased risk of death from all causes (ARI 8.2%, NNH 12). This finding did or did not meet statistical significance depending on the statistical method employed. Some secondary outcome measures assessing morbidity suggested a benefit of intensive insulin therapy. These included a reduction in kidney failure (ARR 3%, NNT 33), earlier weaning from mechanical ventilation, and earlier discharge from the ICU and from the hospital.
The results of this important study are sure to fuel more debate on ideal goals for blood sugar control in the critically ill. The study confirms previous findings that intensive insulin management improves mortality in patients with longer stays in the ICU. As length of stay in the ICU is difficult to predict in advance, the possibility of tight glycemic control increasing mortality in patients with short ICU stays complicates the decision to implement intensive insulin therapy. These results should especially give us pause in extrapolating the original study results to our sick floor patients.—RH