resuscitation with adenocaine and magnesium reduces fluid requirement and improves cardiac function following 72% blood loss in the pig

Abstract

Introduction: Fluid therapy following severe hemorrhagic shock triggers ischemia-reperfusion (I/R) injury and multi-organ dysfunction. The combination of adenocaine (adenosine and lidocaine), and Mg2+ (ALM) has been shown to stabilize cardiac function and hemodynamics after myocardial I/R.

Hypothesis: ALM in 7.5%NaCl at resuscitation: 1) reduces fluid requirements during permissive hypotension and 2) improves post-resuscitation cardiac function.

Methods: Pigs (38kg) were randomized to: Sham (n=5), Sham + ALM (n=5), hemorrhage (n=11), and hemorrhage + ALM (n=9). Animals were subjected to pressure controlled hemorrhage at a target MAP of 35mmHg. After 90 min Ringers acetate and 20ml 7.5% NaCl ± ALM (Adenosine 0.23 mg/kg; Lidocaine 0.64 mg/kg; Mg2+ 0.4 mg/kg) was infused to maintain a target MAP of 50 mmHg (permissive hypotension). After 30min 75% of the shed blood was re-infused ± ALM (Adenosine 0.82 mg/kg; Lidocaine 1.66 mg/kg) and the pigs were observed for 6 hrs. Cardiac function was evaluated by pressure-volume (P-V) analysis.

Results: In the ALM group 40% less fluid was required to maintain a MAP of 50mmHg for 30min (hemorrhage: 41.5ml/kg CI: 27.7-61.8 vs. ALM: 24.7ml/kg CI:19.4-31.5*). During permissive hypotension 7.5% NaCl ALM significantly increased end-systolic pressure by 27% (hemorrhage: 70 mmHg ± 3 vs. ALM: 89 mmHg ± 9*) and cardiac contractility by 64% (dP/dtmax) (hemorrhage: 2622 mmHg/sec ± 331 vs. ALM: 4301 mmHg/sec ± 262*). Treatment with ALM at blood infusion reduced whole body O2 consumption by 27% lasting 30 min into infusion (group difference p<0.05). In addition, systolic function after blood reinfusion, evaluated by the end-systolic P-V relationship and preload recruitable stroke work, was significantly improved in ALM vs. hemorrhage. Furthermore, ALM enhanced relaxation (dP/dtmin) during reperfusion (hemorrhage: -1578 mmHg/sec ± 103 vs. ALM -2178 mmHg/sec ± 189*).

Conclusion: 7.5% NaCl ALM reduced fluid requirements by 40% during permissive hypotension, improved cardiac function and reduced total body O2 consumption following severe hemorrhage. Administration of ALM is effective in minimizing fluid requirements and I/R injury following hemorrhage. (* p<0.05)