The life-saving effect of “adenosine, lidocaine, and magnesium” cocktail during hypovolemic shock: One stone, three birds?

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To the Editor:
Letson and Dobson1 showed that treatment with adenosine, lidocaine, and magnesium (ALM) significantly decreased mortality in a severe hypovolemic shock model with uncontrolled hemorrhage. Similar lifesaving effects of ALM were also observed by the same investigators in swine with either volume-controlled hemorrhagic or septic shock.2–4 We are particularly intrigued by these findings and believe these studies may provide important insights into the treatment of traumatic shock in prehospital or battlefield scenarios. Herein, we suggest further interpretation of the data in an attempt to better understand the physiological mechanisms underlying the unique benefits of the treatment.
The increased blood pressure after ALM treatment during hemorrhagic shock appears to be predominantly due to an increased cardiac performance, as evidenced by improvements in cardiac index, sinus rhythm, and stroke volume (SV), without increases in systemic vascular resistance (SVR) or heart rate.1–4 In the current study, a bolus of ALM normalized SV without affecting the ejection fraction in an uncontrolled hemorrhage model with the blood pressure reduced below 40 mm Hg. These results suggest that, surprisingly, ventricular end diastolic volume and thus venous return were both normalized by the ALM treatment after an uncontrolled hemorrhage. This inotropic effect of ALM is impressive but an important question remains to be answered: why were the venous return and SV maintained or tended to be increased concomitant with loss of blood volume?
An intact venous return observed at 60 minutes after uncontrolled hemorrhagic shock is difficult to imagine but might be possible if ALM can immediately stop the bleeding. In fact, there is evidence that trauma-induced coagulopathy was corrected within 5 minutes after ALM treatment, suggesting that ALM might provide improvements to hemostatic function5 although this has yet to be elucidated in a model with intact coagulation. In the current study, there was a loss of only 10% of total blood volume in the ALM-treated group (estimated by collecting clots and loose abdominal blood with preweighed gauze at the end of the experiment). A moderate venous constriction and capillary fluid shift may have occurred at 60 minutes after bolus ALM (when the ejection fraction was measured after phase one) and thus minimized the decrease in venous return.
Given that the inotropic effect of ALM was reproducibly found in both rodent and swine with hemorrhagic shock,1,2 the beneficial effect on acute blood pressure compensation might be more promising for hemorrhagic or cardiogenic shock than septic or anaphylactic shock, in which the fall in blood pressure is mainly due to vasodilation. In fact, ALM infusion in rat and porcine models of sepsis induced a profound drop in total SVR and systemic pressure.3 It is unclear why ALM markedly decreased SVR in the septic models even though it had no effects on SVR in the hemorrhagic model.2 Adenosine, lidocaine, and magnesium produced clear increases in visceral blood flow in the current study, suggesting that SVR could be decreased but SVR calculations were not provided.1 A more complete understanding of the physiological mechanism(s) underlying the beneficial effect of ALM treatment is important to avoid a potential risk of further decrease in blood pressure induced by ALM treatment. Moreover, although counterintuitive in terms of known compensatory responses to hemorrhage, visceral vasodilation observed with ALM may maintain gut tissue viability, thereby decreasing inflammatory sequelae associated with the loss of the gut barrier. It would be interesting to explore this possibility in future studies. In essence, the profound beneficial effects on cardiac performance may allow the maintenance of blood pressure after a mild hemorrhage without the need to compromise visceral blood flow.
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