Antisecretory Factor May Reduce ICP in Severe TBI—A Case Series

Would this work in hemorrhagic stroke? Reduce the pressure?  WHOM is your doctor and stroke hospital contacting to get that answered? Or will incompetence occur again by DOING NOTHING?

Antisecretory Factor May Reduce ICP in Severe TBI—A Case Series

David Cederberg^1*, Hans-Arne Hansson², Edward Visse¹ and Peter Siesjö¹

• ¹Department of Neurosurgery, Skane University Hospital, Lund, Sweden
• ²Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

Traumatic brain injury (TBI) constitutes a global epidemic. Overall outcome is poor, with mortality ranging from 10 to 70% and significant long-term morbidity. Several experimental reports have claimed effect on traumatic edema, but all clinical trials have failed. Antisecretory factor, an endogenous protein, is commercially available as Salovum^®, which is classified as a medical food by the European Union and has been proven effective in experimental trauma models. It has, however, previously not been tested in humans with severe TBI. We hereby report a case series of five adult patients with severe TBI, treated with Salovum. The objective of the intervention was to evaluate safety and, if possible, its effect on intracranial pressure and outcome. Patients received 1 g Salovum per kilo of body weight divided into six doses per 24 h. Each dose was administered through the nasogastric tube. Patients were scheduled for 5 days of treatment with Salovum. Intracranial pressure was controlled in all patients. In three of five patients, intracranial pressure could be controlled with Salovum and deep sedation (no barbiturates), except during periods of gastroparesis. Five of five patients had a favorable short-term outcome, and four of five patients had a favorable long-term outcome. No toxicity was observed. We conclude that at least three of the five treated patients experienced an effect of Salovum with signs of reduction of intracranial pressure and signs of clinical benefit. In order to validate the potential of antisecretory factor in TBI, a prospective, randomized, double-blind, placebo-controlled trial with Salovum has been initiated. Primary outcome for the trial is 30-day mortality; secondary outcomes are treatment intensity level, intracranial pressure, and number of days at the neurointensive care unit.

Introduction

Traumatic brain injury (TBI) constitutes a global burden despite the fact that mortality and morbidity have been reduced in several countries during the last decades (1, 2). Advances in neurointensive care, cerebral monitoring, and neuroradiology have improved outcome for patients with severe TBI, but the results globally are still poor with a mortality ranging from 10 to 70% and significant long-term morbidity (3).

Traumatic brain injury encompasses several pathogenic mechanisms as primary mechanical injury and hemorrhage followed by secondary events such as vasospasm, inflammation, excitotoxic cell damage, and energy deprivation but also long-term progressive brain tissue degeneration. One common denominator in TBI is cerebral edema, which may cause raised intracranial pressure (ICP) and is a major factor responsible for mortality and morbidity in TBI (4). The pathophysiologic mechanisms of cerebral edema are, however, only partially known (5).

Although several experimental reports have claimed effect on traumatic cerebral edema, all clinical trials have failed (6).

Antisecretory factor (AF) is a 41-kDa endogenous protein proposed to possess both antisecretory and anti-inflammatory effects (7). The exact mechanism of AF is unknown, but it has been proposed to act by modulation of proteasomes, complement, and myeloid cells (8–10). A recent report shows that AF inhibits the NKCC1 ion pump; the latter also has been implicated in the evolution of edema in TBI (11, 12).

Salovum^® is an egg yolk powder enriched for AF and classified as food for specific medical purposes in the EU. Salovum has been used in clinical trials for gastroenteritis and Ménière inflammatory bowel disease, and no toxicity has been reported [Lantmännen Functional Foods AB Besöksadress: S:t Göransgatan 160, Stockholm, Sweden, (13)].

The functional part of AF has been synthesized within a 16-amino-acid peptide, AF16. AF16 and AF have shown effects against cerebral edema and increased ICP in models of herpes encephalitis and TBI (14, 15).

We hereby report the first five patients with severe TBI, treated with the AF-enriched dietary supplement Salovum with the aim to assess ICP control and clinical outcome.

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