The effect of methylene blue on the hemodynamic changes during ischemia reperfusion injury in orthotopic liver transplantation.
After graft reperfusion in orthotopic liver transplantation (OLT), ischemia reperfusion syndrome (IRS) is characterized by persistent hypotension with a low systemic vascular resistance. Methylene blue (MB) has been used as a vasopressor in sepsis and acute liver failure. We investigated the effect of MB on IRS during OLT. Thirty-six patients undergoing elective OLT were randomized to receive either a bolus of MB 1.5 mg/kg before graft reperfusion, or normal saline (placebo). We recorded hemodynamic variables, postoperative liver function tests, and time to hospital discharge. Blood samples were analyzed for arterial lactate concentration, cyclic 3',5'-monophosphate, and plasma nitrite/nitrate concentrations. The MB group had higher mean arterial pressure (P = 0.035), higher cardiac index (P = 0.04), and less epinephrine requirement (P = 0.02). There was no difference in systemic vascular resistance or central venous pressure. Serum lactate levels were lower at 1 h after reperfusion in MB patients, suggesting better tissue perfusion (P = 0.03). In the presence of MB, there was a reduction in cyclic 3',5'-monophosphate (P < 0.001), but not plasma nitrites. Postoperative liver function tests and time to hospital discharge were the same in both groups. MB attenuated the hemodynamic changes of IRS in OLT acting via guanylate cyclase inhibition.


CONCLUSIONS
Methylene blue attenuates the hemodynamic changes of the ischemia reperfusion syndrome in liver transplantation, and this effect involves guanylate cyclase inhibition.
Koelzow
Heike
H
St James's University Hospital, Beckett Street, Leeds, UK.
Gedney
Jacqueline A
JA
Baumann
Janos
J
Snook
Nicola J
NJ
Bellamy
Mark C
MC
D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D008875:Middle Aged; D009573:Nitrites / Q000097:blood; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D009573:Nitrites; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue