Vasopressin and nitroglycerine may reduce bleeding during liver resection surgery

Hepatic hemorrhage is a justifiably feared complication during liver surgery and after traumatic liver injuries. In 1908, J. Hogarth Pringle published his famous paper “Notes on the arrest of hepatic hemorrhage due to trauma” in which he proposed “. by seizing the portal vessels as soon as the abdominal cavity is opened; for by so doing one can obtain a clear field and therefore, time is gained for the treatment of the wound of the liver itself. ” Today this surgical procedure is known as the Pringle maneuver and remains a frequently used vascular clamping technique to combat blood loss during liver surgery and after traumatic liver injuries. Such a nonselective inflow occlusion may, however, have detrimental effects due to the potential of causing liver ischemia, compromise mesenteric outflow, and hemodynamic instability. In order to limit these negative effects, a selective inflow occlusion by hemihepatic or segmental occlusion of the portal vein and/or hepatic artery may be applied. Selective vascular occlusion techniques are particularly useful when resecting parts of the left or right liver lobes. A third possibility to decrease bleeding is to regulate blood pressures within the hepatic venous system. Central venous pressure (CVP) has been used as a surrogate for pressures within the hepatic venous system. Lower CVP has been associated with reduced blood loss, yet this effect remains controversial. Nitroglycerine is frequently used to lower CVP during liver surgery, but may cause unwanted circulatory instability due to systemic vasodilation. Various other measures like increasing the depth of anesthesia, use of epidural analgesia, and fluid restriction may also be applied. Pharmacological interventions may act synergistically with various surgical occlusion techniques and therefore represents a clinically relevant field for further exploration. A group of Swedish researchers from Gothenburg has previously reported the pressure lowering effect of nitroglycerine and independency of body position during liver surgery. They also documented that short-term low to moderate infusion rates of vasopressin reduced hepato-splanchnic blood flow without major changes in hepatic venous and portal venous pressures. In this issue of the Journal Dr. Wis en et al continue this line of research and describe the effects of combining nitroglycerine and vasopressin on splanchnic blood flow and portal and hepatic venous pressure. In otherwise healthy patients undergoing liver resection for hepatic malignancy, a combined infusion of a lowto moderate-dose of vasopressin and nitroglycerine reduced portal and hepatic venous pressure, leading to considerably reduced portal (splanchnic) and hepato-splanchnic blood flow. Lowering the splanchnic blood flow by the use of vasopressin analogs is known to be an effective measure in patients with chronic liver failure, portal hypertension, and hepatorenal syndrome. In patients suffering from severe splanchnic vasodilation, vasopressin analogs cause vasoconstriction via specific vasopressin receptors in smooth muscle cells of splanchnic blood vessels. Translating this knowledge to the field of liver resection in patients with normal splanchnic blood flow and portal vein pressure is a tempting idea. In their study, Dr Wis en et al did find a substantial reduction in hepato-splanchnic blood flow by using vasopressin in combination with nitroglycerine. It is likely that this intervention may reduce blood loss during liver resection, yet it remains to be confirmed in a randomized placebo controlled trial. Relatively few participants, short observation time and the lack of an appropriate time control group are limitations of this study. Clinicians should also be aware that vasopressin may cause harmful microcirculatory disturbances potentially leading to gut ischemia. This side effect was not investigated in the present study by Wis en et al and can only be evaluated in bigger randomized trials. However, the preserved hepatic vein flow in the vasopressin group might indicate that vasopressin does not affect the hepatic arterial buffer response, a prerequisite for liver protection. Are there other drugs or combinations of drugs that could obtain the same effect as vasopressin, while being safer? Norepinephrine is widely used to counteract the drop in arterial blood pressure caused by anesthetic agents and the vasodilatory effects of nitroglycerine. This intervention has merit in that it is cheaper and has similar effects as the vasopressin analog terlipressin in patients suffering from hepatorenal syndrome. Thus, further research should compare the potential of novel pharmacological protocols using vasopressine and norepinephrine and clearly document clinically relevant endpoints. We are sure that Dr. Pringle would have appreciated this work, moving from his innovative approach of restricting fatal blood loss by simple mechanical clamp techniques to controlled pharmaceutical interventions.