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

Abstract

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/Mg^2+, (4) 7.5% NaCl with adenosine/Mg^2+, (5) 7.5% NaCl with lidocaine/Mg^2+, 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 Mg^2+. 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/Mg^2+ and lidocaine/Mg^2+ were mildly bradycardic but not when combined as ALM. A few arrhythmias occurred in 7.5% NaCl group with or without Mg^2+, but no arrhythmias occurred in the other treatment groups.

Conclusion: 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.