Page 53 - JSOM Fall 2023

portable ultrasound machine. Therefore, medics today lack Animals were instrumented as previously described with ECG
logistical options for providing whole blood transfusions to leads, left femoral artery and vein catheters, and a right carotid
multiple casualties and for sustaining polytrauma patients artery sheath for continuous blood pressure measurement
over prolonged periods. and arterial blood sampling. Vital signs and hemodynamics
were monitored continuously (Biopac Systems, Goleta, CA).
To meet the need for a deployable far-forward resuscitation In addition, a 5-French pig-tail catheter was placed into the
fluid capable of extending survivability of polytrauma casual- left ventricle for pressure monitoring and injection of colored
ties when whole blood is unavailable, we developed a multi- microspheres, and a pulmonary artery thermodilution catheter
functional DCR cocktail. The DCR cocktail was built upon (Edwards Life Sciences, Irvine, CA) was inserted via the right
a base of 6% hydroxyethyl starch solution (Hextend; Pfizer, external jugular vein into the pulmonary artery for cardiac
Kalamazoo, MI) to expand intravascular volume. In previous output (CO), and core temperature monitoring.
11
published work, we found that Hextend alone was insuffi-
cient to raise blood pressure during resuscitation of polytrauma A midline laparotomy was performed for splenectomy to
because of TBI-induced systemic vasoplegia. In response, we prevent autotransfusion, and an infrarenal aortotomy wire
added vasopressin to support neurovascular tone and finally was placed to induce an aortic tear of 4-mm internal luminal
fibrinogen concentrate to support hemostasis. Vasopressin and length. The wire was exteriorized through the abdominal in-
Hextend recovered impaired systemic blood pressure responses cision, and the incision was closed at the skin using surgical
after combined TBI with hemorrhage, but also increased in- staples. The right anterior mid femur was then exposed after
ternal blood loss resulting from NCTH. Therefore, fibrinogen incising the skin and performing blunt dissection to prepare
concentrate was added to the cocktail as a hemostatic agent, for percussive femoral fracture.
resulting in decreased internal blood loss, improved blood pres-
sure, and improved vital organ blood flow when given as dis- To induce TBI, pigs were then rotated to the prone position,
crete boluses, according to TCCC doctrine. 11,12 However, with a scalp incision was made, and the cranium was exposed. A
the bolus method of delivery of the cocktail, we observed that 16mm-diameter craniotomy hole was placed rightward of the
blood pressure tended to spike, likely contributing to increased sagittal suture and anterior to the coronal suture. A bolt was
internal blood loss from NCTH. then placed firmly into the craniotomy site, approximating the
intact dura and connected to the fluid percussion device. Ad-
The objective of this study was to further optimize the DCR ditional small craniotomies were made to place a neonatal in-
cocktail as a potential solution for immediate resuscitation traventricular catheter (Phoenix Biomedical, Valley Forge, PA)
of the polytraumatized casualty by determining its most ap- for intracranial pressure (ICP) monitoring (SenSym pressure
propriate intravenous delivery method. We hypothesized that sensor, Sunnyvale, CA). All craniotomy sites were sealed com-
the cocktail would decrease internal hemorrhage and increase pletely with dental cement.
3-hour survival when infused slowly compared with rapid bo-
lus administration by avoiding early spikes in systemic blood Injury and Hemorrhage Protocol
pressure that may exacerbate bleeding. To test this hypothesis, The pigs then underwent a stabilization period after instru-
we tested equal total volumes of the DCR cocktail adminis- mentation for at least 30 minutes, during which baseline mea-
tered as two separate boluses versus a single slow infusion surements were recorded. TBI was then induced using a fluid
using a preclinical swine model simulating battlefield poly- percussion device delivering a 15msec pressure wave of 3 to
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trauma with NCTH. 3.5 atmospheres to the intact dura, as previously described.
The pigs were then rotated to the supine position, and an
open comminuted diaphyseal femoral fracture was induced by
Methods
firing a captive bolt pistol (Schermer Stunner, Model MKL,
We used a previously published porcine model of polytrauma Karl Schermer, Karlsruhe, Germany) directly against the ex-
with hemorrhagic shock with TBI and NCTH to compare bo- posed femur using a 0.22-caliber blank round. Simultaneously,
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lus versus slow infusion of the DCR cocktail. This protocol catheter hemorrhage was started via the left femoral arterial
was approved by the University of Washington Office of Ani- catheter and controlled by computer-driven roller pump, as
mal Welfare and the U.S. Army Animal Care and Use Review previously described. 13–15 At mean arterial pressure (MAP)
Office. Briefly, female Yorkshire swine (Sus scrofa domestica; equal to 50mmHg, the aortic tear injury was created by pull-
Progressive Swine Farms, Woodinville, WA) weighing 20kg ing the aortotomy wire. Catheter hemorrhage was titrated to
to 30kg were used for this study. The animals were sedated achieve MAP equal to 30mmHg until hemorrhagic shock was
using intramuscular ketamine (30mg/kg) (Bioniche Pharma, confirmed by an arterial lactate concentration >2.0mmol/L,
Galway, Ireland), intubated, and provided general anesthesia typically after 15 minutes had elapsed.
using inhaled isoflurane (1%–4%) (VetOne, Boise, ID) for the
remainder of the experiment. Animals were ventilated (Anesco Resuscitation Protocol
SAV 2000 and 2500 ventilators, Anesco, Georgetown, KY), One dose of the DCR cocktail consisted of 7mL/kg of 6%
and fraction of inspired oxygen (FiO ) was titrated to an ar- hydroxyethyl starch in Ringer’s lactate solution (Hextend),
2
terial O saturation >95%, while end-tidal CO (Capnomac vasopressin (0.4U/kg), and fibrinogen concentrate (50mg/kg,
2
2
Ultima, Datex, Madison, WI) was maintained at 35mmHg to RiaSTAP , CSL Behring) in a total fluid volume of 10mL/kg
®
40mmHg. For additional analgesia, intramuscular buprenor- and infused together over 10 minutes using an infusion pump.
phine (0.01mg/kg) (Ben Venue Laboratories, Bedford, OH) Over the first hour of fluid resuscitation, the bolus group re-
was given as a single injection. A warming blanket was used to ceived two 10mL/kg boluses, for a total of 20mL/kg of DCR
maintain normothermic core body temperature (37°C to 38°C cocktail volume. Each individual bolus was infused over 10
[98.6°F to 100.4°F]) and was monitored using a pulmonary minutes using a roller pump, and boluses were separated by
artery catheter. 30 minutes. The infusion group received the same total volume
IV Infusion of a DCR Cocktail Decreases Blood Loss in a Pig Model | 51