Summary & discussion and future perspectives flap complications. Currently, dobutamine is the most used vasoactive medication in microsurgery because it has shown to increase cardiac output, decrease systemic vascular resistance, and increase flap perfusion.8‐10 In several recent retrospective studies with either head and neck patients or breast reconstruction patients no increased flap related complications were demonstrated.11‐13 Phenylephrine and ephedrine have been safely used in these studies. Norepinephrine should be used with caution because it has shown to increase vasoconstriction in musculocutaneous perforators. This vasoconstrictor effect was higher in the perforating veins than that in the perforating arteries in an ex vivo experiment.14 However, in a swine model using pedicled flaps and microsurgical flaps, norepinephrine was used to correct anesthesia‐ induced hypotension and did not affect flap metabolism, which was assessed using microdialysis. The intraoperative use of vasopressor in free flap surgery may not be as harmful as previously feared. The risk and benefits should be carefully weighed in each patient. If adequate MAP can be maintained without high‐volume fluid resuscitation, vasopressors should be avoided. Breast cancer patients have a low comorbidity usually, and if needed, dobutamine in a low dose should be the vasopressor of choice in these patients because the increase of flap perfusion by this medication has been demonstrated. However, in cases where the patient is hypotensive and has already received adequate fluid resuscitation and lightning of anesthesia depth is not possible, vasopressors should be used. Chapter 3 Ischemia and reperfusion injury as the mechanism underlying PFL is summarized, and nitric oxide and its protective role on flap survival in surgical flaps are reviewed in this literature study. In chapter 3, the role of ischemia and reperfusion (IR) injury as the underlying cause for PFL is discussed. The pathophysiology of IR injury in surgical flaps is summarized. In addition, the role of nitric oxide (NO) and the modulation of its metabolism to protect surgical flaps from partial flap necrosis are reviewed in this literature study. This chapter also motivates our choice of using L‐arginine, a precursor of NO, to reduce PFL as described in chapter 6. 115
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