Efficacy of reductive ventricular osmotherapy in a swine model of traumatic brain injury

Abstract

Background: The presence of osmotic gradients in the development of cerebral edema and the effectiveness of osmotherapy are well recognized. A modification of ventriculostomy catheters described in this article provides a method of osmotherapy that is not currently available. The reductive ventricular osmotherapy (RVOT) catheter removes free water from ventricular cerebrospinal fluid (CSF) by incorporating hollow fibers that remove water vapor, thereby providing osmotherapy without increasing osmotic load.

Objective: To increase osmolarity in the ventricular CSF through use of RVOT in vivo.

Methods: Twelve Yorkshire swine with contusional injury were randomized to external ventricular drainage (EVD) or RVOT for 12 hours. MR imaging was obtained. Serum, CSF, and brain ultrafiltrate were analyzed. Histology was compared using Fluor-Jade B and hematoxylin and eosin (H & E) stains.

Results: With RVOT, CSF osmolality increased from 292 ± 2.7 to 345 ± 8.0 mOsmol/kg (mean ± SE, P = 0.0006), and the apparent diffusion coefficient (ADC) in the injury region increased from 0.735 ± 0.047 to 1.135 ± .063 (P = 0.004) over 24 hours. With EVD controls, CSF osmolarity and ADC were not significantly changed. Histologically, all RVOT pigs showed no evidence of neuronal degeneration (Grade 1/4) compared to moderate degeneration (Grade 2.6 ± .4/4) seen in EVD treated animals (P = 0.02). The difference in intracranial pressure (ICP) by area under the curve approached significance at P = .065 by Mann Whitney test.

Conclusion: RVOT can increase CSF osmolarity in vivo after experimental traumatic brain injury (TBI). In anticipated clinical use, only a slight increase in CSF osmolarity may be required to reduce cerebral edema.

Figure 1

RVOT operation showing: A) Water vapor removal, which increases CSF osmolarity and draws water out of tissue, and B) Device schematic with dry air mixture into catheter inlet and humidified air exiting the catheter.

Figure 2

Photograph of RVOT catheter (top) and Traumacath ventricular drain catheter (bottom).

Figure 3

Sagittal T1 MR scan at approximately 2 hours post-injury showing right ventricle outline and outline of RVOT Catheter passing through the anterior part of the ventricle. The craniotomy at the contusion site can be seen posterior to the catheter.

Figure 4

Operative field showing RVOT Catheter (A) entering right frontal area, Timesh covering (B) over contusion in right parietal area, and parenchymal sensors (C) posterior to the contusion.

Figure 5

Peak intra-treatment ICP, showing reduced pressure with RVOT treatment.

Figure 6

Hourly averages of ICP ± SE immediately prior to and during treatment. All data taken with pigs in supine position.

Figure 7

Area under the curve for ICP greater than 20 mmHg (mmHg X time).

Figure 8

Photographs of Fluoro-Jade B stained tissue from trauma region after RVOT (Left) and EVD (right) treatment. Degenerating neuronal cells are clearly evident in the EVD section (Grade = 4), but not in the RVOT section (Grade = 1), where only non-neuronal cells are stained. 10X magnification.

Figure 9

Photographs of hematoxylin & eosin (H&E) stained tissue sections taken from the contusion site demonstrating typical injury severity for graded 2 (left), 3 (middle), and 4 (right). 2.5X magnification.

Figure 10

Comparison of Infusion Osmotherapy and RVOT. Current methods of osmotherapy involve delivery of an osmotic agent, but the agent must be in a solution, so overall fluid volume is increased. With RVOT, osmolarity is increased by removal of water, so overall fluid volume is decreased. Intracranial infusion specifically is contraindicated in cases of cerebral edema.