Granfeldt, Asger, Nielsen, Toben K., Sølling, Christoffer, Hyldebrandt, Janus A., Frøkiær, Jørgen, Wogensen, Lise, Dobson, Geoffrey P., Vinten-Johansen, Jakob, and Tønnesen, Else (2012) Adenocaine and Mg2+ reduce fluid requirement to maintain hypotensive resuscitation and improve cardiac and renal function in a porcine model of severe hemorrhagic shock. Critical Care Medicine, 40 (11). pp. 3013-3025.

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Abstract

Objectives: Hypotensive resuscitation is gaining clinical acceptance in the treatment of hemorrhagic shock. Our aims were to investigate: 1) the effect of 7.5% NaCl with adenocaine (adenosine and lidocaine, AL) and AL with Mg²⁺ (ALM) on fluid requirement to maintain a minimum mean arterial pressure of 50 mm Hg, and 2) the effect of a second bolus of 0.9% NaCl with AL during return of shed blood on cardiac and renal function in a porcine model of hemorrhagic shock.

Design: Pigs were randomized to: Sham (n = 5), Sham + ALM/AL (n = 5), hemorrhage control (n = 11), or hemorrhage + ALM/AL (n = 9). Hemorrhage animals were bled to a mean arterial pressure of 35 mm Hg. After 90 mins, pigs were fluid resuscitated with Ringers acetate and 20 mL 7.5% NaCl with ALM to maintain a target mean arterial pressure of minimum 50 mm Hg. Shed blood and 0.9% NaCl with AL were infused 30 mins later. Hemorrhage control group was subjected to the same protocol but without ALM/AL. Hemodynamics, cardiodynamics (pressure–volume analysis), oxygen consumption, and kidney function were measured for 6 hrs.

Setting: University hospital laboratory.

Subjects: Female farm-bred pigs.

Results: Fluid volume infused during hypotensive resuscitation was 40% less in the 7.5% NaCl-/ALM-treated pigs than controls (25 vs. 41 mL/kg, p < .05). ALM was associated with a significant increase in dp/dtmax, end-systolic blood pressure, and systemic vascular resistance. Return of shed blood and 0.9% NaCl/AL reduced whole body oxygen consumption by 27% (p < .05), and significantly improved the end-systolic pressure–volume relationship and preload recruitable stroke work compared to controls. Glomerular filtration rate in the ALM/AL group returned to 83% of baseline compared to 54% in controls (p = .01).

Conclusion: Resuscitation with 7.5% NaCl ALM increases cardiac function and reduces fluid requirements during hypotensive resuscitation, whereas a second AL infusion during blood resuscitation transiently reduces whole body oxygen consumption and improves cardiac and renal function.

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