Neurochemical Monitoring of Glycerol Therapy in Patients With Ischemic Brain Edema

Abstract

Background and Purpose-Osmotic agents such as glycerol are used to treat brain edema in stroke patients. We investigated the pharmacokinetics of glycerol in brain tissue by cerebral microdialysis. Methods-Patients experiencing large middle cerebral artery infarction were included in this prospective study. O smotic agents are used in acute cerebral ischemia to treat brain edema, particularly in space-occupying stroke where the mass effect may cause further clinical deterioration. Other than mannitol, glycerol is commonly used to treat increased intracranial pressure (ICP). 1 However, a potential rebound effect with increasing ICP following glycerol administration may restrict its use in treating brain edema.We studied the pharmacokinetics of glycerol in brain tissue using cerebral microdialysis in patients requiring ICP treatment with intravenous glycerol. Additionally, we investigated potential effects of glycerol therapy on glutamate, lactate, and pyruvate concentration in cerebral microdialysate. We administered glycerol if standard therapy with 15 g mannitol had only insufficient effects and either spontaneous ICP increase Ͼ20 mm Hg persisted Ͼ10 minutes or pupillary functions were disturbed. Then 25 g of glycerol (250 mL 10% Glycerosteril, Fresenius Kabi) were infused through a central venous catheter over 15 minutes. The following variables were assessed before and every 10 minutes until 80 minutes after drug application: ICP and serum osmolarity and microdialysate concentrations of glycerol, glutamate, pyruvate, and lactate, which were analyzed enzyme-photometrically (CMA 600 Autoanalyser). To account for varying baseline values of glycerol, ICP, and osmolarity, we calculated relative changes at all subsequent time points. Patients and MethodsWe used the Wilcoxon signed rank test to detect differences between each time point and baseline values. Statistical analyses were performed with StatView statistical software. A PϽ0.05 was considered statistically significant. Data are presented as meanϮSEM. ResultsA total of 16 episodes with ICP crises in 7 patients (3 female, 4 male) experiencing large middle cerebral artery infarction were included in this study. Their mean age was 51.7 with a range between 35 and 65 years.Cerebral glycerol concentrations rose immediately after intravenous glycerol administration from 73.9Ϯ17.0 mol/L by a maximum of 350% within 20 minutes. Subsequently, glycerol decreased gradually to a nonsignificantly different level at 60 minutes after the infusion had ended. Conversely, ICP (baseline 25Ϯ2.4 mm Hg) rapidly decreased by almost 50% and remained significantly lower for 50 minutes with a short rebound at 40 minutes. In contrast, serum osmolarity (baseline 305Ϯ5.6 mOsm/L) increased only briefly by Ϸ3% (Figure 1).

Interaction between Brain Chemistry and Physiology after Traumatic Brain Injury: Impact of Autoregulation and Microdialysis Catheter Location

“…Our data, revealing sustained differences in the levels of lactate, LP ratio, LG ratio, and glycerol between two catheter locations, which remained even after controlling for possible influences from confounding parameters, supports the presence of baseline differences between ''normal'' and ''perilesional'' tissue types. Higher glycerol levels in perilesional tissue, as a marker of cellular membrane breakdown, may reflect the degree of structural injury, manifesting in cellular death or apoptosis, although contribution from extracerebral sources of glycerol cannot be excluded, especially taking into account the higher likelihood of blood-brain barrier disruption in more injured tissue, even though no glycerolcontaining medications (Berger et al, 2005) were used in these patients. Higher lactate, LP, and LG ratios are more likely to indicate persistent metabolic derangement, e.g., acquired and sustained mitochondrial dysfunction (Verweij et al, 2000).…”

Cerebral microdialysis of interleukin (IL)-1ß and IL-6: extraction efficiency and production in the acute phase after severe traumatic brain injury in rats

“…In the extracellular fluid (ECF), liquid found between the cells containing proteins and electrolytes, profound disturbances have been demonstrated in concentrations of glutamate and aspartate and energy-related metabolites such as lactate, pyruvate, adenosine, inosine and hypoxanthine after brain injury and these changes correlate with the severity of the injury [2,6,29,31,[33][34][35].…”

Treating Intracranial Hypertension in Patients with Severe Traumatic Brain Injury during Neurointensive Care

“…As recently shown, the composition of the enema used might also directly influence the cerebral compartment as cerebral extracellular glycerol was significantly increased [96]. Whether the absorbed glycerol is able to equally reduce elevated ICP and improve CPP as observed following intravenous infusion remains to be determined.…”