Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
Status:
Completed
Trial end date:
2014-09-01
Target enrollment:
Participant gender:
Summary
Traumatic brain injury (TBI) is among the leading causes of trauma death and disability in
both civilian and military populations. The damage that occurs at the instant of trauma
cannot be modified; the secondary injuries that occur afterward are the impediments to
recovery and can be influenced by the physician. Cerebral ischemia is the most important
secondary event that determines outcome following TBI. To minimize ischemic episodes once the
patient has arrived at the hospital, most treatments are aimed at optimizing cerebral
perfusion pressure (CPP). The cornerstones of these treatments include mannitol, to reduce
intracranial pressure (ICP), and catecholamines, such as phenylephrine (PE), to increase mean
arterial pressure (MAP), but these agents have undesired side effects. Nevertheless, once
they lose potency, there are few alternatives. The main objective of this proposal to develop
a new therapeutic option for CPP management in TBI patients using arginine vasopressin (AVP).
AVP is the endogenous anti-diuretic hormone. It is FDA-approved for use in the diagnosis and
treatment of diabetes insipidus, for the prevention and treatment of post-operative abdominal
distention, and in abdominal radiography to dispel interfering gas shadows. It has been used
off-label for several other conditions. There is minimal information on its therapeutic
potential after TBI. The investigators have demonstrated that AVP during fluid resuscitation
rapidly restored hemodynamics, CPP, and improves acute survival in a clinically-relevant
model of TBI. The investigators observed similar short term benefits after chest and liver
trauma. Nevertheless, AVP has actions that could mask any short term benefit. The
investigators have already defined risks and benefits of AVP therapy, relative to PE, in four
different clinically-relevant laboratory model. The investigators now plan to evaluate this
new therapy relative to the current evidence-based guideline for CPP management in TBI
patients.
The working hypothesis is that the risk/benefit profile for AVP is equal, or superior to, PE
at equi-effective doses for the management of CPP following TBI. A corollary is that a higher
CPP can be safely tolerated with AVP vs catecholamines.
THE INVESTIGATORS AIM TO: Determine whether AVP is safe and effective to maintain CPP = 60 mm
Hg in TBI patients.