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Ulinastatin Effective in Treating Impairment of Pulmonary Gas Exchange After Lower Extremity Surgery: Presented at ASA

By Lexa W. Lee

NEW ORLEANS -- October 20, 2009 -- Ulinastatin is effective in treating pulmonary gas exchange impairment, which occurs within 1 day after tourniquet deflation in lower-extremity surgery, according to study results presented at the 2009 Annual Meeting of the American Society of Anesthesologists (ASA).

A pneumatic tourniquet, traditionally used to provide a bloodless field during extremity surgery, is associated with ischaemia-reperfusion (I/R) injury. While acute lung injury as a remote sequela of severe lower-torso I/R has been demonstrated experimentally in animal models, it remains uncertain as to whether tourniquet application within a safe time limit of 1.5 hours would have the same effect on the lungs in patients undergoing extremity surgery under intraspinal anaesthesia, stated lead investigator Lina Lin, 1st Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang Province, China, speaking here at a poster presentation on October 17.

Ulinastatin is a medication that has been used to treat shock and manage extracorporeal circulation. Ulinastatin inhibits neutrophils from releasing free radicals and chemical mediators, but whether it is effective in treating tourniquet-induced I/R injury has been unproven.

The aim of this study was to determine whether applying a tourniquet during extremity surgery results in I/R that impairs pulmonary gas exchange postoperatively, and if so, whether ulinastatin can attenuate the lung injury.

The study enrolled 26 ASA II (mild systemic disease) surgery patients aged 25 to 65 years, with a tourniquet duration time between 60 to 90 minutes. The patients were randomly divided into 2 groups. There were 14 patients in the control group and 12 in the ulinastatin group, who were given 6,000 U/kg of ulinastatin 10 minutes before tourniquet inflation.

Radial arterial blood gases, plasma malondialdehyde (MDA, a marker for lipid peroxidation), and cytokines interleukin (IL)-6, IL-8, and IL-10 levels were measured just before tourniquet inflation (T0), 1 hour after inflation (T1), 30 minutes (T2), 2 hours (T3), 6 hours (T5), and 24 hours (T6) after tourniquet deflation. The difference in alveolar-arterial oxygen partial pressure (AaDO₂) and respiratory index (RI) were calculated.

At T4, partial pressure of oxygen (PaO₂) was remarkably decreased, compared to T0. AaDO₂ and RI were significantly increased (both P < .01). Levels of plasma MDA, serum IL-6, and IL-8 began to increase significantly after T3 (P < .01), peaking at T4 (P < .05). The concentrations of these measurements gradually decreased, but remained high at T5 in the control group (P < .01). PaO₂ was higher in the ulinastatin group; AaDO₂ and RI were significantly decreased at T4 (P < .05; P < .01); and circulating MDA, IL-6, and IL-8 were remarkably lower in the ulinastatin group after T2 or T3 (P < .05; P < .01). Serum IL-10 concentration was undetectable in both groups at all time points.

The researchers concluded that pulmonary gas exchange becomes impaired postoperatively within 1 day after tourniquet deflation (inflation lasting 60 to 90 minutes). The impairment can be effectively treated by ulinastatin 6,000 U/kg, which inhibits lipid peroxidation and overproduction of IL-6 and IL-8.

[Presentation title: Effect of Ulinastatin on Gas Exchange Impairment in Patients Undergoing Lower Extremity Surgery. Abstract A280]

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