BACKGROUND: Safe and reversible occlusion of vascular structures is needed when performing nephron sparing surgery. Renal artery clamping is frequently performed during partial nephrectomy, despite the known incidence of permanent renal damage from temporary ischemia. The use of an intraluminal, atraumatic, occlusive agent that can be reliably reversed has great potential in such cases. Poloxamer 407 (Legoo^TM) is a nontoxic, non-ionic polymer with rapidly reversible solute-gel transition behavior. Formulations exist that allow for the injection of a liquid at low temperatures that form a solid hemostatic plug at body temperature. Poloxamer 407 was studied as a temporary vascular occlusive agent during partial nephrectomy.
METHODS: Temporary renal vascular occlusion was obtained with varying concentrations of purified Poloxamer 407 (13.5-20%, w/w). Fifteen pigs placed under general anesthesia underwent retroperitoneal exposure of the right kidney. Following cannulation of the renal artery, varying concentrations of Polyoxamer 407 were injected into the renal artery at different rates. Renal ischemia was confirmed by gross appearance of the kidney and by the absence of either renal or segmental arterial flow by vascular Doppler study. Lower pole heminephrectomy with closure of the collecting system was then performed. Time to reperfusion was determined with and without instillation of cold saline. Both the excised portion of kidney and the reperfused organ were fixed in formalin, followed by pathological assessment of Hematoxylin and eosin stained tissue sections for evidence of renal damage.
RESULTS: All concentrations of Poloxamer 407 produced vascular occlusion. Higher concentrations of poloxamer (17.5-20%, w/w) produced a renal artery plug, whereas lower concentrations (13.5-15% , w/w) produced distal arterial branch occlusion. Rapid injection (1-4 sec) of solution 17.5-20% (w/w) produced a renal artery plug in 11 cases, while slower injection (6-30 sec) of 13.5-15% (w/w) resulted in distal occlusion (4/4 cases). A concentration of 13.5% (w/w) injected over 20-30 seconds was found to be optimal as this produced distal vascular occlusion while maintaining a main renal artery pulse. Bloodless heminephrectomy was performed successfully in all circumstances. Renal reperfusion was achieved within 10-80 minutes of injection in all animals. Longer time to reperfusion was found when higher concentrations (17.5-20%, w/w) and volumes of poloxamer were used. All specimens evaluated by pathology revealed no evidence of renal damage or presence of residual poloxamer.
CONCLUSIONS: Poloxamer 407 effectively and reliably creates temporary renal vascular occlusion, allowing for bloodless partial nephrectomy in a swine model. Two important parameters in the effective usage of Poloxamer 407 involved concentration and delivery time. Optimization of these two parameters allowed for shorter time to reperfusion secondary to faster poloxamer dissolution. This novel class of compound will potentially allow maintenance of blood flow to unaffected renal parenchyma while occluding perfusion to the planned area of resection leading to decreased risk of permanent ischemic renal injury. Additional research into the intraluminal application of Poloxamer 407 in laparoscopic and robot assisted partial nephrectomy is ongoing.
*These authors contributed equally