Ultra-small intravenous bolus of 7.5% NaCl/Mg²⁺ with adenosine and lidocaine improves early resuscitation outcome in the rat after severe hemorrhagic shock in vivo.
OBJECTIVE
Much controversy exists over the fluid composition for hypotensive resuscitation. We previously showed that addition of 6% Dextran-70 or hetastarch to 7.5% NaCl led to heart instability and mortality. Our aim was to examine the early resuscitative effects of 7.5% NaCl with adenosine, lidocaine, and magnesium (ALM) on hemodynamics and mortality in a rat model of severe hemorrhagic shock.


METHODS
Male fed Sprague-Dawley rats (300-450 g, n = 48) were anesthetized and randomly assigned to one of six groups (n = 8): (1) Untreated, (2) 7.5% saline, (3) 7.5% NaCl/Mg²⁺, (4) 7.5% NaCl with adenosine/Mg²⁺, (5) 7.5% NaCl with lidocaine/Mg²⁺, and (6) 7.5% NaCl/ALM. Hemorrhagic shock was induced by phlebotomy until mean arterial pressure (MAP) was 35 mm Hg to 40 mm Hg and continued for 20 minutes (40% blood loss). Animals were left in shock for 60 minutes at 34°C. 0.3 mL (~3.5% of shed blood) was injected as a 10-second bolus into the femoral vein. Lead II electrocardiography, arterial pressures, MAP, heart rate, and rate-pressure product were monitored.


RESULTS
Untreated rats experienced severe arrhythmias and 38% mortality. There were no other deaths. 7.5% NaCl alone failed to maintain MAP after 5 minutes and was significantly improved with Mg²⁺. At 60 minutes, the MAP for 7.5% NaCl alone was 36 mm Hg compared with 48 mm Hg for the magnesium group. 7.5% NaCl/ALM led to a significantly higher MAP (57-60 mm Hg at 45-60 minutes). The higher MAP was associated with up to a 2-fold increase in arterial diastolic pressure. Both 7.5% NaCl with adenosine/Mg²⁺ and lidocaine/Mg²⁺ were mildly bradycardic but not when combined as ALM. A few arrhythmias occurred in 7.5% NaCl group with or without Mg, but no arrhythmias occurred in the other treatment groups.


CONCLUSIONS
Ultra-small intravenous bolus of 7.5% NaCl with ALM led to a significantly higher MAP, higher diastolic rescue, and higher rate-pressure product compared with other treatment groups. The possible clinical and military applications for permissive hypotensive resuscitation are discussed.
Heart Research Laboratory, Department of Physiology and Pharmacology, School of Biomedical Sciences, James Cook University, Townsville, Queensland, Australia.
Hayley L
HL
Letson
Geoffrey P
GP
Dobson
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005440:Fluid Therapy; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage*; D017616:Magnesium Compounds / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000628:therapy*; D012965:Sodium Chloride / Q000008:administration & dosage*
D000889:Anti-Arrhythmia Agents; D017616:Magnesium Compounds; D012965:Sodium Chloride; D008012:Lidocaine; D000241:Adenosine