Recommendations for Wound Healing Therapies for CLI
COR	LOE	Recommendations
I	B-NR	An interdisciplinary care team should evaluate and provide comprehensive care for patients with CLI and tissue loss to achieve complete wound healing and a functional foot.229,339–341
See Online Data Supplement 44.		The management of patients with CLI and nonhealing wounds should include coordinated efforts for both revascularization and wound healing, because the risk of limb-threatening infections remains until complete wound healing is achieved. The structure and activities of interdisciplinary care teams for CLI may vary according to several factors, including the local availability of resources. Previous groups have described various combinations of activities of this team, which are in addition to revascularization and include functions such as wound care, infection management, orthotics, and prosthetics (see Online Data Supplement 34a for a complete list of functions). Coordination of these activities and some degree of organized team structure are recommended, as opposed to ad hoc or unstructured referrals among various specialty clinicians not involved in interdisciplinary care.
		Ambulatory patients with PAD and nonhealing foot ulcers should be considered for efforts to prevent amputation. The components of this effort may include revascularization, offloading, treatment of infection, and wound care. The long-term outcome of the limb is excellent when complete wound healing can be achieved.339Revascularization should be coordinated with the efforts of clinicians who manage foot infections, provide offloading, and achieve complete wound healing, either through medical therapy, surgical options, or a combination thereof. Coordinated and timely interdisciplinary care can achieve excellent limb outcomes for patients with PAD and nonhealing foot wounds.229,339–341
I	C-LD	In patients with CLI, wound care after revascularization should be performed with the goal of complete wound healing.339
See Online Data Supplement 44.		A comprehensive plan for treatment of CLI must include a plan for achieving an intact skin surface on a functional foot. One study demonstrated a limb salvage rate of 100% at 3 years in a cohort of patients with CLI who achieved complete wound healing with endovascular revascularization and dedicated wound care.339 Before revascularization, the interdisciplinary care team should devise a plan to achieve the goal of complete wound healing. After successful revascularization, most patients with gangrene of the foot are evaluated for minor amputation with staged/delayed primary closure or surgical reconstruction when feasible.342–344 Negative-pressure wound therapy dressings are helpful to achieve wound healing after revascularization and minor (ie, digit or partial foot) amputation when primary or delayed secondary closure is not feasible.345,346 Spontaneous amputation, or autoamputation, of gangrenous digits should be reserved for palliation in patients without options for revascularization.345,347,348
		Other evidence-based guidelines relevant to those with nonhealing foot wounds following revascularization cover the full spectrum of diabetic foot problems349 or separately consider the management of infection,225,350 offloading,351 and wound care.352 To date, there are no RCTs or high-quality studies that have focused on wound healing adjuncts in limbs with severe PAD (eg, topical cytokine ointments, skin substitutes, cell-based therapies intended to optimize wound healing).
IIb	B-NR	In patients with CLI, intermittent pneumatic compression (arterial pump) devices may be considered to augment wound healing and/or ameliorate severe ischemic rest pain.353
See Online Data Supplement 44.		A systematic review of studies that used intermittent pneumatic compression devices specifically designed to augment arterial perfusion of the lower extremities suggests that these may provide modest clinical benefit (specifically, decreased amputation rates and improved QoL) in patients with CLI who were ineligible for revascularization.353 The potential benefit appears to outweigh the low risk associated with the use of these devices.
IIb	C-LD	In patients with CLI, the effectiveness of hyperbaric oxygen therapy for wound healing is unknown.354
See Online Data Supplement 44.		The literature evaluating the utility of hyperbaric oxygen therapy has focused on patients without severe PAD and has not demonstrated a long-term benefit on wound healing or improving amputation-free survival when compared with sham treatment.355 There are no published studies evaluating the role of hyperbaric oxygen therapy for patients with nonreconstructible PAD. One small RCT that focused on patients with foot ulcers and PAD (ABI <0.80 or TBI <0.70) for whom no revascularization was planned demonstrated a significant decrease in ulcer area at 6 weeks, but no significant differences in ulcer size at 6 months, complete ulcer healing at 6 weeks or 6 months, and major or minor amputations.354 Further research on the utility of hyperbaric oxygen therapy in this context is needed.
III: No Benefit	B-R	Prostanoids are not indicated in patients with CLI.356
See Online Data Supplement 43.		A systematic review and meta-analysis concluded that RCTs have not demonstrated meaningful long-term clinical benefit from the administration of prostanoids to patients with CLI attributable to nonreconstructible PAD.356