RESUMO
UNLABELLED: Outpatient wound care centers are encountering patients with more complex wounds and an increased incidence of concomi- tant complicating comorbidities. As the population ages, patients with chronic wounds are presenting with multiple active disease processes that cause initiation of the wounds, impede wound healing, and pre- clude safely proceeding with surgical procedures, under anesthesia, to treat those wounds. METHODS: Four warfarin-anticoagulated patients presented with large, full-thickness, necrotic, lower extremity wounds induced by hematomas from blunt trauma. Two of the wounds under- went scalpel debridement under local anesthesia while continuing anticoagulation. Following brief initial wound care with normal saline wet-to-moist dressing changes, continuous negative pressure therapy at 125 mmHg was initiated and continued for all wounds until the ex- pansive tissue defects were decreased for 23.8 ± 3.2 days. All wounds were treated with application of a living bilayered skin substitute (LSS) in an outpatient setting while maintaining therapeutic anticoagulation. RESULTS: All wounds completely epithelialized (100% closure) by 39.0 ± 21.9 weeks. One wound was completely relieved of its deep tissue defect to total epithelialization with one application of LSS. The largest wound (21.0 cm x 14.5 cm x 2.8 cm) with the greatest undermining (5 cm) was relieved of its tissue defect with a combination of nega- tive pressure therapy and three applications of the LSS. The second largest wound (8.6 cm x 24.0 cm x 2.1 cm), which had an exposed knee joint capsule, required two applications of LSS. These results indicate that patients with large, full-thickness, necrotic, lower extrem- ity wounds caused by traumatic hematomas while on anticoagulation therapy, can be appropriately managed as outpatients with aggressive sharp debridement under local anesthesia, negative pressure therapy for relief of the tissue defect, and bilayered skin substitute application to induce epithelial coverage. CONCLUSION: This approach eliminates the need for cessation of anticoagulation therapy and the use of more complex surgical procedures, such as myocutaneous flaps and skin grafts in patients with multiple underlying comorbid conditions.
RESUMO
Heparin has been shown to decrease total vascular resistance while protamine stimulates endothelium-dependent vasodilation. This study was undertaken to determine whether heparin and/or protamine could enhance endothelium-derived relaxing factor (EDRF), as determined by nitric oxide (NO) production. Porcine carotid artery endothelial cells (PAECs) were seeded on multiwell plates, grown to confluence, and exposed to heparin (1-20 U/ml) or protamine (50-200 microg/ml) for 24 hours. With the addition of the NO synthase inhibitor, N(G)-monomethyl-L-arginine (NMMA), to heparin and/or protamine, the medium samples were collected in one hour. In a parallel clinical study, plasma samples were collected from patients undergoing cardiopulmonary bypass (CPB). The NO production was measured as reflected by the formation of nitrite (NO2-) and nitrate (NO3-), the stable end-metabolites of NO. NO production by PAECs was significantly increased by heparin > or = 5 U/ml or protamine > or = 50 microg/ml in a concentration-dependent manner. The increase of NO production was prevented by the addition of NMMA. In CPB patients, plasma NO2-/NO3- concentration was significantly increased after heparin administration compared to the preoperative value, at which time the mean plasma heparin level was 4.9+/-0.5 U/ml. Following slow protamine infusion, there was no significant difference in plasma NO2-/NO3- concentration compared to preoperative value. In conclusion NO production increases following exposure of PAECs to heparin and/or protamine. In patients, NO concentration significantly increased after heparin administration by IV bolus, but not with a slow infusion of protamine after CPB.