Intravenous surfactant treatment tested in paraplegic dogs

Abstract

Hydrophilic polymers, both surfactants and triblock polymers, are known to seal defects in cell membranes. In previous experiments using laboratory animals, we have exploited this capability using polyethylene glycol (PEG) to repair spinal axons after severe, standardized spinal cord injury (SCI) in guinea pigs. Similar studies were conducted using a related co-polymer Poloxamer 188 (P 188). Here we carried out initial investigations of an intravenous application of PEG or P 188 (3500 Daltons, 30% w/w in saline; 2 mL/kg I.V. and 2 mL/kg body weight or 300 mL P 188 per kg, respectively) to neurologically complete cases of paraplegia in dogs. Our aim was to first determine if this is a clinically safe procedure in cases of severe naturally occurring SCI in dogs. Secondarily, we wanted to obtain preliminary evidence if this therapy could be of clinical benefit when compared to a larger number of similar, but historical, control cases. Strict entry criteria permitted recruitment of only neurologically complete paraplegic dogs into this study. Animals were treated by a combination of conventional and experimental techniques within approximately 72 h of admission for spinal trauma secondary to acute, explosive disk herniation. Outcome measures consisted of measurements of voluntary ambulation, deep and superficial pain perception, conscious proprioception in hindlimbs, and evoked potentials (somatosensory evoked potentials [SSEP]). We determined that polymer injection is a safe adjunct to the conventional management of severe neurological injury in dogs. We did not observe any unacceptable clinical response to polymer injection; there were no deaths, nor any other problem arising from, or associated with, the procedures. Outcome measures over the 6-8-week trial were improved by polymer injection when compared to historical cases. This recovery was unexpectedly rapid compared to these comparator groups. The results of this pilot trial provides evidence consistent with the notion that the injection of inorganic polymers in acute neurotrauma may be a simple and useful intervention during the acute phase of the injury.