The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19107, USA.
Journal of Neurosurgery (Impact Factor: 3.23). 11/2004; 101(4):594-9. DOI: 10.3171/jns.2004.101.4.0594
Source: PubMed

ABSTRACT Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2.
Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2.
Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

  • Source
    Frontiers in Pharmacology 05/2014; 5:100. DOI:10.3389/fphar.2014.00100
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multilevel functional data is collected in many biomedical studies. For example, in a study of the effect of Nimodipine on patients with subarachnoid hemorrhage (SAH), patients underwent multiple 4-hour treatment cycles. Within each treatment cycle, subjects' vital signs were reported every 10 minutes. This data has a natural multilevel structure with treatment cycles nested within subjects and measurements nested within cycles. Most literature on nonparametric analysis of such multilevel functional data focus on conditional approaches using functional mixed effects models. However, parameters obtained from the conditional models do not have direct interpretations as population average effects. When population effects are of interest, we may employ marginal regression models. In this work, we propose marginal approaches to fit multilevel functional data through penalized spline generalized estimating equation (penalized spline GEE). The procedure is effective for modeling multilevel correlated generalized outcomes as well as continuous outcomes without suffering from numerical difficulties. We provide a variance estimator robust to misspecification of correlation structure. We investigate the large sample properties of the penalized spline GEE estimator with multilevel continuous data and show that the asymptotics falls into two categories. In the small knots scenario, the estimated mean function is asymptotically efficient when the true correlation function is used and the asymptotic bias does not depend on the working correlation matrix. In the large knots scenario, both the asymptotic bias and variance depend on the working correlation. We propose a new method to select the smoothing parameter for penalized spline GEE based on an estimate of the asymptotic mean squared error (MSE). We conduct extensive simulation studies to examine property of the proposed estimator under different correlation structures and sensitivity of the variance estimation to the choice of smoothing parameter. Finally, we apply the methods to the SAH study to evaluate a recent debate on discontinuing the use of Nimodipine in the clinical community.
    Journal of the American Statistical Association 10/2013; 108(504):1216-1229. DOI:10.1080/01621459.2013.826134 · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients admitted to the neurocritical care unit (NCCU) often have serious conditions that can be associated with high morbidity and mortality. Pharmacologic agents or neuroprotectants have disappointed in the clinical environment. Current NCCU management therefore is directed toward identification, prevention, and treatment of secondary cerebral insults that evolve over time and are known to aggravate outcome. This strategy is based on a variety of monitoring techniques including use of intraparenchymal monitors. This article reviews parenchymal brain oxygen monitors, including the available technologies, practical aspects of use, the physiologic rationale behind their use, and patient management based on brain oxygen.
    Neurosurgery clinics of North America 07/2013; 24(3):427-39. DOI:10.1016/ · 1.54 Impact Factor