Immediate Versus Delayed Skin Grafting of Free Muscle Flaps for Limb Salvage: Does Timing Matter?

In the domain of microsurgical reconstruction, particularly for complex lower extremity (LE) wounds, the decision of when to perform skin grafting over a free muscle flap (MFF) remains critical. A recently published study in Microsurgery (2025) by Karen R. Li and colleagues, titled “Immediate Versus Delayed Skin Grafting of Free Muscle Flaps for Limb Salvage: Does Timing Matter?”, attempts to resolve this clinical conundrum by analyzing whether delaying the placement of split-thickness skin grafts (STSGs) improves outcomes, particularly in medically comorbid patients.

This retrospective analysis, conducted over 12 years at MedStar Georgetown University Hospital, involved 91 patients who underwent LE MFF and STSG for limb salvage. Patients were categorized into two groups: immediate skin grafting performed concurrently with flap inset, and delayed grafting, typically around 12 days later. The delayed group included patients with a higher burden of comorbidities—diabetes mellitus (DM), peripheral vascular disease (PVD), chronic kidney disease (CKD), and more severe inflammatory markers.

What the Study Found

The study’s overarching goal was to determine the impact of graft timing on success rates. The findings are as revealing as they are clinically relevant:

Graft failure rate was observed in 31.5% of all patients, with no statistically significant difference between immediate (27%) and delayed (42.3%) groups.
Multivariable regression analysis showed that elevated HbA1c levels, low serum albumin, and history of Charcot arthropathy were independently associated with graft failure—not the timing of STSG.
Delayed STSG patients had significantly higher Charlson Comorbidity Index scores (mean 5.6 vs. 3.7), indicating greater systemic disease burden.
Despite this, their outcomes were similar to those of the healthier immediate group, suggesting that delayed grafting could mitigate some of the risks posed by comorbidities.

Surgical Strategy: Timing Guided by Physiology

The authors explain that the decision to delay grafting was based on intraoperative and systemic indicators: suspected flap compromise, hemodynamic instability, excessive bleeding, or severe flap edema. In these cases, the muscle flap was temporarily covered with acellular dermal matrices (ADMs) such as Integra or Primatrix and negative-pressure wound therapy (NPWT) was employed before definitive grafting.

The logical rationale? A more stable, better-perfused flap may offer a superior substrate for graft survival after initial healing and vascular ingrowth, especially in high-risk patients.

Interestingly, although NPWT was used significantly more in the delayed group (54% vs. 5%), it did not independently predict better outcomes in multivariate analysis. The implication here is that while NPWT supports edema management, systemic patient health—particularly nutrition and diabetic control—is paramount.

Comorbidity Matters More Than Timing

One of the key takeaways from this study is that patient comorbidities outweigh the timing of skin grafting in influencing outcomes. Elevated HbA1c (a proxy for long-term glucose control) increased the odds of graft failure by 50% per unit increase, while each 1 g/dL increase in serum albumin reduced the risk by 70%. A history of Charcot arthropathy was associated with nearly 9 times the odds of graft failure.

These results support the notion that meticulous preoperative optimization, rather than procedural timing alone, is essential for successful graft take.

Patient-Centric Implications

From a patient’s perspective, this study highlights the importance of shared decision-making and realistic expectation-setting. Patients with poorly controlled diabetes or poor nutritional status may benefit more from a staged approach to reconstruction, despite the extended hospital stay and need for a second surgery.

Furthermore, limb salvage surgeries must be integrated into a broader plan of wound healing optimization, with early nutritional support, glycemic control, and vascular health evaluation forming the foundation.

Future Directions

This study raises important questions for future prospective, randomized trials:

Can systematic protocols for delaying STSG in comorbid patients reduce graft failure rates?
How can perioperative nutritional and glycemic management be integrated into limb salvage algorithms?
What role do emerging biologics and smart wound dressings play in optimizing outcomes?

Until such evidence emerges, this study provides a pragmatic framework for microsurgeons: in comorbid patients, when in doubt, delay the graft.

Key Points Highlighted:

Graft failure rates are high (31.5%) in muscle flap reconstructions requiring STSG, particularly among patients with diabetes and poor nutrition.
Delayed skin grafting did not worsen outcomes and may equalize results between comorbid and non-comorbid groups.
Elevated HbA1c, low serum albumin, and Charcot arthropathy were the strongest predictors of graft failure.
NPWT and ADM can support flap bed maturation before delayed grafting.
A tailored approach to STSG timing—guided by comorbid status, intraoperative bleeding, and flap health—is essential.

References:

Li, K.R., Rohrich, R.N., Episalla, N.C., et al. (2025). Immediate Versus Delayed Skin Grafting of Free Muscle Flaps for Limb Salvage: Does Timing Matter? Microsurgery, 45:e70055. https://doi.org/10.1002/micr.70055