Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. METHODS: Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. RESULTS: A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. CONCLUSIONS: High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

Trends in the use of pulmonary artery catheterization in the aneurysmal subarachnoid hemorrhage population.

Use of the pulmonary artery catheter (PAC) has been controversial since the late 1980s. Multi-center observational and randomized controlled trials (RCTs) have concluded that PACs fail to decrease mortality. Subsequently, studies have looked for a decline in PAC use that corresponds to the literature and have indeed found that it exists. However, none to date have looked primarily at trends in the aneurysmal subarachnoid hemorrhage (aSAH) population. This study uses the Nationwide Inpatient Sample (NIS) from 2000-2010 to identify trends in PAC use among patients with aSAH. Trend analysis was assessed using a multivariable regression model with a calculation of slope of PAC frequency over time for pre-2005 and post-2005. Trends in mortality and routine discharge were also assessed for the same time period. 363,096 SAH patients were extrapolated using survey weights, of whom 6,988 had a PAC. Over time, PAC use declined, with a significant downward shift in the year 2005. Analyses also showed a decrease in mortality over the same time period. Our results show that PAC use among patients with aSAH decreased from 2000 to 2010. Similar to other studies, the decline appears to be temporally related to RCTs that showed a lack of benefit from PAC. Studies such as these have the potential to influence clinical practice through illumination of shifting opinions and approaches.