Automated Closed-Loop Resuscitation of Traumatic Brain Injury and Hemorrhagic Shock With Trigeminal Nerve Stimulation
Abstract
The mortality and morbidity due to trauma has been substantially reduced in the last few decades, mostly due to improvements in medical evacuation, transportation, and definitive care. Nevertheless, 87% of battlefield deaths occur before reaching a medical facility, and nearly a quarter of these injuries are considered potentially survivable. In this sub-group, most of the deaths are associated with bleeding with a drop in blood pressure (hemorrhagic shock or HS) with or without traumatic brain injury (TBI). Therefore, any strategies that can maintain blood pressure for long enough to gain control of hemorrhage and restore intravascular volume could be lifesaving. Unfortunately, few if any, new treatments have been developed for this early post-injury period. Resuscitation with intravenous fluids, vasopressors, and blood constitute what is referred to as “definitive resuscitation,” but these are not available to the patient until the medic arrives or the patient gets to a field hospital. Several critical minutes, or hours, can be lost in this process. Therefore, a new resuscitation method is needed for the prehospital trauma care. It is well recognized that HS and TBI, either alone, or worse still in combination (TBI+HS), remain the major causes of mortality and long-term disability in combat casualties. One of the main treatment goals in both TBI and HS is to restore blood pressure and get blood to the brain and to other vital organs as soon as possible. The trigeminal nerve is the largest of the cranial nerves and is responsible for sensation over the face and tongue. It has been known that the cranial nerves are connected to the sympathetic and parasympathetic (autonomic) nervous systems – the parts of the nervous system that control many vital physiological functions such as blood pressure and cerebral blood flow. However, this connection has not been widely studied or previously exploited for treatment purposes. We have recently shown that electrical stimulation of the trigeminal nerve (upper face) is capable of ameliorating some of the important physiological consequences of TBI and HS by modulating both sympathetic and parasympathetic nervous system activity to increase blood pressure, improve cerebral perfusion, and decrease inflammation. In a rat model of TBI, we have shown that trigeminal nerve stimulation (TNS) decreases secondary brain injury. In addition, in a rat model of severe HS, we have shown that TNS increases survival time without conventional fluid resuscitation. In the proposed research, we will develop a system of non-invasive TNS to perform closed-loop resuscitation to treat combat injury with HS and TBI compounded by HS. First, we will optimize the TNS parameters based on improvement in hemodynamic stability in HS in a rat model. Second, we will compare the relative effectiveness of TNS and fluid resuscitation, both singly and in combination, in the treatment of HS. Third, we will determine the relative effectiveness of these two approaches to resuscitation in the treatment of TBI compounded by HS. We will then develop a fully automated closed-loop resuscitation system for TNS. Finally, we will test this closed-loop system in a large animal (swine) model of HS. Our approach is unique in that, for the first time, we will stimulate the body’s own (endogenous) protective mechanisms to ameliorate the adverse consequences of HS and TBI+HS. Due to its simplicity and safety, this approach allows for early use in the mass causality and combat-related fields with limited medical care resources after bleeding from any cause, with or without TBI. Such an approach, if successful, will extend the temporal window of opportunity for deploying severe injured civilians/Soldiers to definitive treatment in a more controlled environment and save numerous lives, especially for the combat Soldiers. This project is obviously of great relevance to our Warfighters, but will also have a tremendous
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810773
Entities
People
- Chunyan Li
Organizations
- The Feinstein Institute for Medical Research
- United States Army