Impact of different antithrombotics on the microcirculation and viability of perforator-based ischaemic skin flaps in a small animal model

Abstract

The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical ischaemia model was used to evaluate the effects of different perioperatively administered pharmaceutical agents on tissue ischaemia and to assess the potential additional haemorheological or vasodilative effects of antithrombotics on flap microcirculation. Combined laser Doppler flowmetry and remission spectroscopy revealed an increase in certain microcirculation parameters in most groups in comparison with saline controls, and these changes correlated with flap survival. Clopidogrel and hirudin significantly improved the amount of viable flap tissue in comparison with controls, while unfractioned heparin had a negative effect on flap survival. Low molecular weight heparin, aspirin, pentoxifylline, and hydroxyethyl starch had no impact on the amount of viable flap tissue. A higher complication rate was observed in all experimental groups, but only clopidogrel had a negative impact on the flap viability. Our results add to the body of evidence supporting the conclusion that perioperative antithrombotic treatment improves flap survival. Clopidogrel and hirudin are effective pharmacological agents that significantly increased the viability of perforator-based skin flaps in rats, but at a higher risk of postoperative bleeding.

Figure 1. Impact of various pharmaceutical agents on the microcirculation.

Depicted are the mean laser spectrophotometric values for the oxygen saturation (SO₂ in percent), haemoglobin levels (Hb in AU), blood velocity (in AU) and blood flow (in AU) over the course of the experiment. Measurements were conducted preoperatively (light), after raising the flap (medium) and on day 7 (dark). Error bars indicate the standard error. Abbreviations: (NaCl) saline solution, (ASA) acetylsalicylic acid, (Clop) clopidogrel, (Hep) heparin, (Clex) clexane, (Lep) lepirudin, (Px) pentoxifylline, and (HES) hydroxyethyl starch.

Figure 2. Impact of various pharmaceutical agents on the flap vitality.

Box plot graph illustrating the amount of vital tissue (in percent) in the control group (saline solution, NaCl) and the experimental groups ((ASA) acetylsalicylic acid, (Clop) clopidogrel, (Hep) heparin, (Clex) clexane, (Lep) lepirudin, (Px) pentoxifylline, (HES) hydroxyethyl starch). The small circles indicate statistical outliers. Clopidogrel and lepirudin showed statistically significantly larger vital flap areas in comparison with saline controls.

Figure 3. Clinical aspects of epigastric perforator flaps.

Upper left: Raised epigastric flap based on a single perforator (white broken circle) after bipolar cautery of the superficial epigastric vessels and all but one deep inferior perforator. The remaining perforator was handled with great care to avoid vasospasm. Lower left and middle: The same flap on postoperative day 7 after daily clopidogrel treatment. Lower left: In addition to the strong, pulsating, main perforator (white circle), several new vessels (black circles) can be observed. Middle: The vital flap on day 7 after clopidogrel treatment with almost no necrotic area. The re-established vascular network is visible through the skin. Right: Massive haematoma under a necrotic flap on day 7 after clopidogrel treatment.