Page 130 - JSOM Fall 2020

Far Forward Gaps in Hemorrhagic Shock
and Prolonged Field Care

An Update of ALM Fluid Therapy for Field Use

Geoffrey P. Dobson, PhD*; Hayley L. Letson, PhD

ABSTRACT
2–5
Future expeditionary missions are expected to occur in more environments. “For every casualty who dies of wounds in
remote austere environments where combat medics and ca- a medical treatment facility (MTF)”, he wrote, “as many as 9
sualties may have to wait up to 7 days before resupply or have already died.” Over 3 decades later, this capability gap
2
safe evacuation. Currently, there is no effective fluid ther- remains wide open. A 2012 US Joint Trauma System study
apy for hemorrhagic shock (HS) at the point-of-injury and reported 87.3% of combat deaths in the Iraq and Afghani-
continuum-of-care over this extended period. We have been stan wars occurred before the casualty reached an MTF (4,596
developing a small-volume IV or IO ALM therapy for non- deaths), with 24.3% deemed potentially survivable. Of those
4,6
compressible HS and have shown in preclinical models that deaths, 91% were from hemorrhage with 67% being truncal
it extends survival to 3 days, reduces abdominal bleeding (noncompressible), 19% junctional, and 14% peripheral-ex-
by 60%, blunts inflammation, corrects coagulopathy, pre- tremity. Similarly, in the civilian prehospital setting, rapid
6
serves platelet function, and prevents immunodeficiency. The transport of the wounded to a tertiary trauma care facility
ALM-survival phenotype is associated with an upregulation of to resuscitate and surgically intervene is not always possible.
7
the master genes of metabolism and mitochrondrial biogene- A second capability gap that remains wide open in the far
sis in heart and brain and a downregulation in the periphery. forward combat environment is prolonged field care to sta-
Future translational studies will investigate the timing and na- bilize the casualty and reduce secondary injury progression.
ture of the “switch” and extend survival to 7 days. We will Secondary injury progression is one of the most critical win-
also discuss some of the controversies of ALM resuscitation in dows of opportunity to reduce morbidity and mortality. Time
pigs, present our Systems Hypothesis of Trauma (SHOT), and is the biggest killer in both these acute and continuum-of-care
discuss future clinical safety trials before field use. scenarios.

Keywords: hemorrhage; trauma; survival; genetics; metabo- The First ALM “Idea”:
lism; inflammation; military medicine; resuscitation
Human Translation into Cardiac Surgery
Twenty years ago, GPD asked if it was possible to pharmaco-
logically manipulate the human heart to operate more like the
Today, defense of the homeland focuses on placing heart of a natural hibernator for improved protection during
military capabilities as far forward as possible. cardiopulmonary bypass or valvular surgery. 8–10 Within 10
—Joint Operating Environment 2035 1p25 years, we translated a high-dose ALM cardioplegia from an
isolated rat heart into human cardiac surgery. We chose ade-
Background: The New Combat Environment: nosine (A) to inhibit the sinoatrial node and reduce the atrial
Challenge of Change and ventricular action potential (AP) duration (A1 receptor
subtype and A1 linked opening of K ATP channels), lidocaine (L)
The 2016 Joint Operating Environment document posits that to reduce AP amplitude by arresting Na fast channels, and
+
over the next 20 years there will be a wide range of threats magnesium (M) to stabilize the membrane and protect against
and persistent conflicts. Future expeditionary missions are ex- reperfusion arrhythmias. We theorized this strategy will ar-
11
pected to occur in more remote, austere environments, where rest the heart at its resting membrane potential and avoid the
combat medics and casualties may have to wait up to 5 to 7 use of high potassium, which depolarizes the membrane and
days before resupply or evacuation. promotes “ischemic” injury currents. 12,13 Two prospective, ran-
domized, clinical trials have shown the ALM cardioplegia to be
Hemorrhagic Shock: A Widening Gap superior to high potassium cardioplegia with less days in hos-
14,15
in Far Forward Medicine pital. After surgery, the heart is reanimated in sinus rhythm
with 10 times lower concentrations of ALM, which is facili-
In 1984, Col Ronald Bellamy launched a challenge to develop tated because its resting membrane potential is “ready to fire.”
new resuscitation fluid therapies to treat combatants with This resuscitation strategy led to a second idea; namely, could
severe blood loss and reduce preventable deaths in austere low-dose ALM resuscitate the heart after major trauma? 10
*Correspondence to geoffrey.dobson@jcu.edu.au
Drs Dobson and Letson are from the Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University,
Queensland, Australia.

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