Effects of therapy with methylene blue on hemodynamics and gas exchange in septic shock

Introduction

Death of patients from septic shock is usually associated to severe reduction of systemic vascular resistances and severe hypotension despite elevated cardiac output values. The mediator of vasodilatation, nitric oxide (NO), is synthesised by the inducible NO synthase. Excess NO synthesis during septic shock causes abnormal vasodilatation [1].

A possible therapeutic approach is represented by the pharmacological inhibition of the enzyme guanylate cyclase by methylene blue (MB), a long known and safe pharmacological approach for the treatment of nitrate intoxication and methemoglobinemia [2].

The aim of the present study is the evaluation of short term effects of methylene blue on hemodynamics and gas exchange in patients with septic shock.

Materials and methods

We studied five patients (three males, two females, mean age 56.6 ± 16.9, APACHE II 25.8 ± 5.6, SOFA score 13.8 ± 3.0) with septic shock (three post-surgery of aortic aneurysm surgery, one intracerebral bleeding, one encephalitis), informed consent was obtained by patients or relatives. All patients had a Swan-Ganz pulmonary artery and a fiberoptic femoral artery catheter inserted and were monitored with the COLD device (PULSION, München). All variables were measured prior to the injection of an endovenous bolus of methylene blue (3 mg/kg body weight in 10 min) and 20 min and 2 h after bolus administration. Values are indicated as means ± SD, P values < 0.05 were considered as significant.

Results

Mean arterial pressure (MAP) raised immediately after rnethylene blue injection (60 ± 9.2 versus 70.8 ± 11.9), systemic vascular resistances (SVR) raised (938.7 ± 177.9 versus 1262.7 ± 686.9), whereas cardiac index and heart rate did not change. Right ventricle indexed blood volume raised (145.9 ± 16.6 versus 161.4 ± 20.2), whereas left ventricle indexed blood volume was reduced (379.6 ± 158.2 versus 289 ± 211.1). Extra-vascular lung water augmented (8.5 ± 6.3 versus 12.5 ± 11.4). The measured shunt fraction did not change but the PaO₂/FiO₂ index worsened (230 ± 108 versus 219.5 ± 98.3). Two hours after injection of methylene blue MAP, SVR as well as right and left intracardiac volumes remained superior to baseline levels.

Conclusion

In our patients methylene blue induced an increase in systemic vascular resistances and of mean arterial pressure without affecting cardiac output. More difficult remains the evaluation of pharmacological effects on cardiac volumes and on final outcome of these septic shock patients. Further investigations will have to demonstrate effectiveness of methylene blue in the treatment of septic shock.