Adenosine, lidocaine, and magnesium support a high flow, hypotensive, vasodilatory state with improved oxygen delivery and cerebral protection in a pig model of noncompressible hemorrhage

Letson, Hayley L., Granfeldt, Asger, Jensen, Thomas H., Mattson, Thomas H., and Dobson, Geoffrey P. (2020) Adenosine, lidocaine, and magnesium support a high flow, hypotensive, vasodilatory state with improved oxygen delivery and cerebral protection in a pig model of noncompressible hemorrhage. Journal of Surgical Research, 253. pp. 127-138.

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Abstract

Background: Noncompressible hemorrhage is the leading cause of preventable death in military and civilian trauma. Our aim was to examine the effect of adenosine, lidocaine, and magnesium (Mg2+; ALM) on cardiovascular and cerebral function in a porcine hepatic hemorrhage model.

Materials and methods: Pigs (59.1 ± 0.34 kg) were anesthetized, instrumented, and randomly assigned into sham (n = 6), saline controls (n = 10) or ALM (n = 10) groups before laparoscopic liver resection. After 30 min, groups received 4 mL/kg 3% NaCl ± ALM bolus (Phase 1) followed 60 min later with 3 mL/kg/h 0.9% NaCl ± ALM drip (4 h; Phase 2), then transfusion. Hemodynamics, carotid artery flow, and intracranial pressure were measured continuously. Microdialysis samples were analyzed for metabolites.

Results: Saline controls had 20% mortality (mean survival time: 307 ± 38 min) with no ALM deaths over 6 h. Bolus administration increased mean arterial pressure (MAP) in both groups, and drip led to further increases to 62 ± 10 mmHg in controls compared with a steady fall to 47 ± 8 mmHg in ALM group at 240 min. The lower MAP was associated with a dramatic fall in systemic vascular resistance and improved oxygen delivery. ALM drip significantly increased cardiac output and stroke volume with lower dP/dtMin, indicating a less stiff heart. ALM drip also significantly decreased cerebral perfusion pressure, reduced cerebral oxygen consumption (28%), and reduced brain glycerol (60%), lactate (47%), and relative expression of hypoxia-inducible factor (38%) compared with saline controls.

Conclusions: ALM therapy improved cardiac function and oxygen delivery by lowering systemic vascular resistance after noncompressible hemorrhage. ALM also appeared to protect the brain at hypotensive MAPs with significantly lower cerebral perfusion pressure, lower O2 consumption, and significantly lower cortical lactate and glycerol levels compared to saline controls.

Item ID: 63863
Item Type: Article (Research - C1)
ISSN: 1095-8673
Keywords: Noncompressible hemorrhage; ALM; Far forward; Hypotensive resuscitation; Porcine
Copyright Information: ª2020 Elsevier Inc. All rights reserved.
Funders: U.S. Special Operations Command (USSOCOM)
Projects and Grants: USSOCOM W81XWH-USSOCOM-BAA-15-1
Date Deposited: 04 Aug 2020 02:20
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 10%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110305 Emergency Medicine @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50%
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