Vasopressin Versus Catecholamines for Cerebral Perfusion Pressure Control in Brain Injured Trauma Patients
| Status: | Completed |
|---|---|
| Conditions: | Hospital, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/7/2015 |
| Start Date: | September 2008 |
| End Date: | January 2015 |
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.
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.
This is a randomized, controlled, open-label clinical trial comparing vasopressin and
catecholamines for cerebral perfusion pressure (CPP) control after a traumatic brain injury
(TBI).
Once a neurosurgeon is consulted for a patient presenting with a TBI, they will review entry
criteria and refer to study personnel to obtain informed consent.
After informed consent, subjects will be randomized into one of the 2 groups to receive
either a catecholamine at the discretion of the attending physicians or vasopressin (AVP). A
6 hour dose of non-study drug will be permitted prior to initiation of study drug. The
amount of study drug will be titrated to maintain cerebral perfusion pressure within normal
limits. Subjects will be followed until they can maintain their CPP without vasopressor
medication. Data collection will include amount and duration of vasopressor therapy and
resulting cerebral perfusion pressure and time until successful weaning from vasopressor
therapy.
All subsequent clinical care will be at the discretion of the attending physician.
The standard protocol/procedure for the discontinuation of drugs in each arm of the study is
as follows: Vasopressors are discontinued in a step-wise fashion, regardless of the specific
agent or the specific ICU patient population. In patients with severe traumatic brain injury
(TBI), cerebral perfusion pressure (CPP) is maintained between 60 and 70 mmHg with
vasopressors. When intracranial pressure (ICP) begins to correct (decrease), vasopressors
are titrated downward slowly to maintain CPP. This continues until ICP is normalized and
systemic hemodynamics are able to support a normal CPP. At this point, vasopressors are
withdrawn completely. This process is standard regardless of the choice of vasopressor.
catecholamines for cerebral perfusion pressure (CPP) control after a traumatic brain injury
(TBI).
Once a neurosurgeon is consulted for a patient presenting with a TBI, they will review entry
criteria and refer to study personnel to obtain informed consent.
After informed consent, subjects will be randomized into one of the 2 groups to receive
either a catecholamine at the discretion of the attending physicians or vasopressin (AVP). A
6 hour dose of non-study drug will be permitted prior to initiation of study drug. The
amount of study drug will be titrated to maintain cerebral perfusion pressure within normal
limits. Subjects will be followed until they can maintain their CPP without vasopressor
medication. Data collection will include amount and duration of vasopressor therapy and
resulting cerebral perfusion pressure and time until successful weaning from vasopressor
therapy.
All subsequent clinical care will be at the discretion of the attending physician.
The standard protocol/procedure for the discontinuation of drugs in each arm of the study is
as follows: Vasopressors are discontinued in a step-wise fashion, regardless of the specific
agent or the specific ICU patient population. In patients with severe traumatic brain injury
(TBI), cerebral perfusion pressure (CPP) is maintained between 60 and 70 mmHg with
vasopressors. When intracranial pressure (ICP) begins to correct (decrease), vasopressors
are titrated downward slowly to maintain CPP. This continues until ICP is normalized and
systemic hemodynamics are able to support a normal CPP. At this point, vasopressors are
withdrawn completely. This process is standard regardless of the choice of vasopressor.
Inclusion Criteria:
- Age >/= 18 yrs,
- Primary admission to the hospital within 8 h after injury
- Closed head injury
- Potential for intracranial pressure monitoring
Exclusion Criteria:
- Pregnant or nursing women
- Hemodynamic instability after initial resuscitation
- Vasopressor therapy for greater than 6 hours
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