Optimizing perioperative care in autologous breast reconstruction: a narrative review

Introduction

Autologous breast reconstruction represents one of the most advanced applications of reconstructive breast surgery, combining technical precision with substantial impact on patient well-being after mastectomy (1-3). Continuous refinement in flap design, preoperative imaging, and intraoperative optimization have improved safety, minimized donor-site morbidity and enhanced patient satisfaction (4-6).

Parallel to these technical achievements, perioperative care has increasingly been recognized as a cornerstone of successful outcomes. Evidence-based perioperative pathways have standardized patient management and significantly improved recovery and complication rates (7-11). However, beyond these established frameworks, several physiologic and perioperative strategies remain underexplored in the specific setting of autologous breast reconstruction.

Growing clinical and experimental evidence suggests that modulation of perioperative physiology—through improved oxygenation, metabolic balance, nutritional optimization, and refined wound management—may further enhance microvascular outcomes and patient recovery (12,13). These areas, although not entirely new, have historically received limited discussion within reconstructive literature and are now gaining renewed attention as complementary tools to existing perioperative protocols (14).

This narrative review aims to synthesize and contextualize emerging or underrepresented perioperative strategies in autologous breast reconstruction. By integrating physiological rationale with available clinical evidence, we aim to highlight future opportunities for innovation and optimization in microsurgical breast reconstruction. We present this article in accordance with the Narrative Review reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-539/rc).

Methods

This work was conceived as a narrative review providing a focused overview of emerging strategies for perioperative optimization in autologous breast reconstruction, emphasizing on physiologically based interventions that may complement established perioperative protocols.

A literature search was performed in PubMed (MEDLINE, Bethesda, MD, USA) and Scopus (Elsevier, Amsterdam, The Netherlands), supplemented by manual screening of reference lists from key systematic reviews and consensus statements related to autologous breast reconstruction. The search included publications up to October 2025. Studies addressing perioperative interventions, physiological optimization, or recovery outcomes in microsurgical breast reconstruction—or in related surgical fields with comparable perioperative considerations—were included.

Only articles published in English were included. The selection prioritized studies providing conceptual or clinical insights relevant to perioperative physiology and recovery. The narrative structure was organized thematically around recurrent domains identified in the reviewed literature, encompassing hyperbaric oxygen therapy (HBOT), negative pressure wound therapy (NPWT), perioperative protein and carbohydrate optimization, antioxidant strategies, and drain management for infection prevention. A summary of the search strategy is presented in Table 1.

A total of 1,317 articles were retrieved through the combined PubMed and Scopus searches. Following relevance-based screening according to the predefined inclusion criteria, 125 studies were selected for inclusion in this narrative review. The identification and selection process is summarized in Figure 1.

Figure 1 Visual summary of evidence identification and selection. This schematic outlines the process by which records were identified, screened by title and abstract, assessed at full-text level, and subsequently prioritized for inclusion in the narrative synthesis based on clinical relevance to autologous breast reconstruction, methodological robustness, and contribution to the understanding of perioperative physiological mechanisms. The diagram is provided to enhance transparency and readability and does not reflect systematic or scoping review methodology.

Results

From established enhanced recovery after surgery (ERAS) elements to emerging perioperative strategies

The concept of ERAS was first introduced in colorectal surgery as a structured, multidisciplinary approach to reduce perioperative stress and accelerate functional recovery (14,15). Over the last decade, these principles have been successfully adapted to breast reconstruction, leading to shorter hospitalizations, improved patient satisfaction, and reduced opioid requirements without increasing complication or readmission rates (7-10,16).

In autologous breast reconstruction, the ERAS framework integrates evidence-based interventions across the pre-, intra-, and postoperative continuum. As outlined by the ERAS Society consensus for breast reconstruction, consistent elements include preoperative counseling, limited preoperative fasting with carbohydrate loading, perioperative thromboprophylaxis, multimodal and opioid-sparing analgesia, goal-directed fluid therapy, maintenance of normothermia, prompt catheter and drain removal, early ambulation, and early advancement of oral diet (17). Although institutional variations exist, these principles remain the cornerstone of modern perioperative management in microsurgical breast reconstruction.

Nevertheless, perioperative optimization represents a dynamic process rather than a fixed checklist. Several physiological domains that extend beyond the classical ERAS framework—such as tissue oxygenation, metabolic modulation, micronutrient and protein optimization, and local wound control—have received comparatively little attention within reconstructive literature. These emerging concepts, supported by a growing body of clinical and experimental evidence, may provide new avenues to refine perioperative management and further enhance microvascular outcomes and patient recovery in autologous breast reconstruction.

HBOT

HBOT consists of the intermittent inhalation of 100% oxygen at pressures greater than atmospheric levels, typically between 2.0 and 2.5 ATA (≈203–253 kPa absolute). This transient hyperoxia produces a several-fold increase in plasma oxygen tension, thereby enhancing oxygen diffusion to hypoperfused tissues. Experimental models demonstrate that HBOT promotes fibroblast proliferation, collagen deposition, angiogenesis, and bacterial clearance, while modulating ischemia–reperfusion injury by reducing leukocyte adherence and reactive oxygen species (ROS)–mediated endothelial damage (18-20). André-Lévigne et al. confirmed that HBOT improves re-epithelialization and neovascularization in ischemic wounds, primarily through upregulation of VEGF and TGF-β signaling pathways (21). Early work by Nemiroff et al. also showed synergistic effects between HBOT and radiotherapy in experimental models, supporting improved soft-tissue tolerance and repair capacity (22).

The physiologic rationale for HBOT in reconstructive surgery builds on these mechanisms. In irradiated tissues, microvascular fibrosis, endothelial dysfunction, and chronic hypoxia impair wound healing and flap integration. Marx et al. demonstrated that irradiated bone exhibits significantly reduced tissue oxygen tension, which normalizes after HBOT, allowing for increased capillary density and improved osteoblastic activity (23). These findings were later extended to skin and subcutaneous tissue, where HBOT enhances oxygen-dependent collagen synthesis and mitigates late radiation-induced fibrosis (24,25). Clinical studies in patients with late radiation toxicity following breast-conserving therapy showed improvement in pain, edema, and skin elasticity after HBOT (26,27). The Cochrane review by Bennett et al. further corroborated moderate-quality evidence supporting HBOT for radiation-related soft-tissue and bony necrosis (28).

In breast reconstruction, particularly in patients with a history of radiation therapy, perioperative HBOT has emerged as a potential adjunct to optimize microvascular outcomes. Scampa et al. conducted a preliminary retrospective comparative study in postirradiated patients undergoing autologous breast reconstruction and found no statistically significant differences in postoperative complications between patients receiving perioperative HBOT and those who did not, although the authors suggested a potential benefit that warrants further prospective investigation (29). Meier et al. conducted a retrospective case–control study of secondary autologous breast reconstruction after radiotherapy and observed comparable complication rates between groups, with a trend toward fewer postoperative events in patients receiving perioperative HBOT, although the difference did not reach statistical significance (30). More recently, Idris et al. performed a systematic review of HBOT for complications in nipple-sparing mastectomy and reconstruction, reporting consistent improvements in ischemic flap salvage and infection control across small case series and retrospective cohorts, although the overall evidence remains limited and low-level (31). These findings align with prior reports of HBOT-facilitated recovery in compromised free flaps from other anatomical regions (32-37).

Despite these encouraging signals, evidence supporting the routine use of HBOT in autologous breast reconstruction remains limited. Heterogeneity in treatment protocols—particularly in timing (pre- vs. postoperative setting), session number, and pressure parameters—precludes definitive conclusions. Moreover, most studies to date are retrospective and underpowered. The ISOO-MASCC-ASCO clinical practice guideline on osteoradionecrosis prevention stated that HBOT is not recommended as standard of care for all irradiated patients but may be considered in selected high-risk cases or in patients with delayed wound healing, ideally as part of multidisciplinary management (38).

In summary, HBOT represents a physiologically sound, low-risk adjunct that may enhance microvascular outcomes in irradiated or ischemic tissue environments. While preliminary evidence suggests potential benefits in autologous breast reconstruction, its role should be individualized based on patient risk profile and local availability. Future prospective trials are warranted to clarify optimal timing, dosing protocols, and cost-effectiveness in this patient population.

NPWT

NPWT applies controlled sub-atmospheric pressure over a sealed incision to enhance wound stability and healing. The underlying mechanisms are well established: macrodeformation approximates wound edges and reduces lateral tension, while microdeformation transmits microscopic mechanical forces that stimulate angiogenesis, fibroblast proliferation, and collagen synthesis (39-41). Together, these effects improve tissue perfusion, reduce edema, and promote granulation tissue formation while maintaining a moist, protected environment and facilitating exudate clearance (39-41). Experimental and translational studies have also shown that NPWT modulates inflammatory cytokines and matrix metalloproteinase activity, contributing to accelerated epithelialization and reduced local inflammation (42). International consensus recommendations highlight its role as an adjunct in incisions at high risk of breakdown—such as those under significant tension or ischemia, or in patients with obesity, diabetes, immunosuppression, or other comorbidities (43). Broader evidence from abdominal surgery supports these physiologic principles: prophylactic NPWT over closed abdominal incisions significantly reduced wound complications compared with standard closure (44).

In reconstructive breast surgery, NPWT has been applied to two distinct anatomical regions: the recipient site—the breast envelope or mastectomy flaps—and the donor site—typically the abdominal incision in deep inferior epigastric perforator (DIEP) or transverse rectus abdominis myocutaneous (TRAM) flap harvest. While both share similar wound-healing mechanisms, the clinical objectives differ. At the recipient site, closed-incision negative pressure wound therapy (ciNPWT) has been used to improve flap perfusion and reduce ischemic or infectious complications. Kim et al. reported a significant reduction in mastectomy-flap necrosis (8.9% vs. 23.5%; P=0.03) and overall complications (11.1% vs. 27.9%; P=0.019) when ciNPWT was applied over the reconstructed breast following immediate expander placement (43). Similarly, a 2022 systematic review including oncoplastic and reconstructive cases concluded that ciNPWT reduced overall surgical-site complications compared with standard dressings, particularly in high-risk patients. Vidya et al. also observed reduced wound breakdown and hospital stay, suggesting that ciNPWT may support early discharge within enhanced recovery pathways (44). From an economic standpoint, Gabriel and Maxwell (45) demonstrated measurable cost savings per patient when ciNPWT was applied after reconstructive procedures, mainly due to fewer wound complications and shorter hospitalization. Gabriel et al. (46) further confirmed improved clinical outcomes and lower complication-related costs in patients undergoing immediate breast reconstruction with ciNPWT. Device characteristics may also influence results: Singh et al. (47) compared two ciNPWT systems in breast surgery and found that foam-based devices achieved significantly lower rates of surgical-site complications and dehiscence compared with multilayer absorbent systems and standard dressings. Randomized data remain limited; in a prospective randomized clinical trial (RCT) on mastectomy patients, Larsen et al. (48) found no significant reduction in seroma volume with ciNPWT, although drainage duration was shorter in the sentinel-node subgroup.

In autologous breast reconstruction, NPWT is primarily used at the donor site to reduce wound dehiscence, seroma formation, and tension along the abdominal incision. Dunson et al. (49) reported that ciNPWT significantly reduced abdominal donor-site wound dehiscence in autologous breast reconstruction, reinforcing its specific benefit in DIEP and TRAM flaps. The most recent meta-analysis (2025; 13 studies, 2,882 patients) reported a 42% reduction in donor-site dehiscence [odds ratio (OR) 0.58, 95% confidence interval (CI): 0.42–0.79], with no significant differences in infection or seroma rates (50). These findings have been reinforced by large multicenter cohorts: Escobar-Domingo et al. (51) analyzed over 700 patients (1,125 flaps) and found that ciNPWT at DIEP donor sites was significantly associated with lower rates of donor-site wound dehiscence and surgical-site infection. In contrast, Haas et al. (52) reported that in their single-institution cohort of abdominal donor sites after DIEP flap reconstruction, the use of incision-negative pressure therapy did not result in statistically significant reductions in donor-site complications (adjusted OR 0.549, 95% CI: 0.277–1.088; P=0.08), highlighting the need for careful patient selection and standardized postoperative care. Individual series have provided complementary insights—Chegireddy et al. (53) found a trend toward reduced drainage time, Kang et al. (54) reported significantly lower drain volumes and earlier removal in high-BMI patients, and Fang et al. (55) described improved scar quality and tension distribution in a pilot study following DIEP reconstruction. Siegwart et al. (56) found reduced major but not minor donor-site complications, stressing that uniform postoperative management protocols are essential for reproducibility and comparison across centers. Finally, Müller-Sloof et al. (57) conducted a RCT on DIEP donor sites demonstrating a significant reduction in wound dehiscence with ciNPWT (19% vs. 41%) and identifying it as an independent predictor of improved healing.

Overall, the evidence suggests that ciNPWT offers distinct benefits depending on the site of application. At the recipient site, its effect is more apparent in high-risk patients and in incisions under tension, while at the donor site, the most consistent finding is reduced dehiscence, with heterogeneous effects on infection and seroma. The integration of NPWT into perioperative pathways for microsurgical breast reconstruction should therefore be individualized according to patient risk profile, anatomical site, and institutional protocols. Future research should clarify the optimal site of application, pressure settings, and duration, as well as cost-effectiveness within enhanced recovery frameworks. Additionally, prospective studies may explore whether NPWT could play a role in improving flap physiology or reducing venous congestion in select free-flap reconstructions.

Antioxidant and metabolic modulation

Oxidative stress plays a pivotal role in the pathophysiology of ischemia–reperfusion injury and postoperative wound healing. During major reconstructive procedures—particularly in free-flap surgery—temporary ischemia followed by reperfusion generates a surge of ROS that depletes endogenous antioxidant reserves (58,59). This imbalance contributes to endothelial dysfunction, edema, and microvascular stasis, ultimately threatening flap viability. Consequently, antioxidant and metabolic therapies have emerged as promising adjuncts to enhance microcirculatory stability and tissue recovery (59).

Among these strategies, glutathione occupies a central role as the main intracellular antioxidant responsible for maintaining redox homeostasis and detoxifying ROS. Experimental data strongly support its protective function: in ischemia–reperfusion models, intravenous glutathione administered before reperfusion significantly reduced hydrogen-peroxide and lipid-peroxidation levels, preserved nitric-oxide bioavailability, and limited mitochondrial injury (60). Arrivi et al. demonstrated in patients with acute coronary syndromes that glutathione sodium salt infusion markedly attenuated oxidative stress and endothelial damage, supporting the potential for perioperative applications in microsurgery (60). Similarly, Cheung et al. and Kuo et al. showed in ischemic models that glutathione and its nitric-oxide–releasing derivative (GSNO) improved perfusion and flap survival by suppressing peroxynitrite formation and inducible nitric-oxide-synthase expression—mechanisms directly relevant to free-flap physiology (61,62). These findings collectively suggest that glutathione supplementation could mitigate oxidative damage and reperfusion-related endothelial dysfunction in high-demand reconstructive settings. Further studies are warranted to define dosing, timing, and patient selection criteria for its clinical translation.

Other antioxidant agents acting through convergent mechanisms may provide complementary benefits. Vitamin C (ascorbate) supports collagen synthesis and regenerates oxidized glutathione, while N-acetylcysteine (NAC) serves as a glutathione precursor and direct ROS scavenger; both have demonstrated efficacy in attenuating oxidative stress and inflammation in surgical contexts (63,64). In a systematic review and meta-analysis, Suter et al. found that perioperative high-dose intravenous vitamin C was associated with reduced postoperative pain, opioid consumption, and markers of oxidative stress and inflammation in noncardiac surgical patients, suggesting potential applicability in reconstructive settings (65). Selenium, an essential cofactor of glutathione peroxidase, contributes to peroxide detoxification and maintenance of redox potential (66). Notably, an ongoing randomized controlled trial (ClinicalTrials.gov identifier NCT05327348) is currently evaluating high-dose intravenous vitamin C in patients undergoing free-flap reconstructive surgery, underscoring the growing translational interest in antioxidant strategies for microsurgical patients (67).

Beyond redox regulation, arginine-based metabolic modulation has shown promising effects on microvascular perfusion. Booi et al. conducted a randomized double-blind trial in patients undergoing TRAM-flap breast reconstruction and found that perioperative intravenous arginine supplementation significantly improved microcirculation in the distal (zone IV) portion of the flap, the region most vulnerable to ischemia (68). Arginine exerts its effects primarily through enhanced nitric-oxide synthesis, leading to vasodilation, improved tissue oxygenation, and augmented collagen deposition. These findings are supported by broader literature on immunonutrition, in which arginine and omega-3 fatty acids have demonstrated synergistic effects in reducing postoperative infections and improving wound healing (14,69). Klek et al. summarized a decade of clinical research on perioperative immunonutrition in surgical cancer patients, confirming that arginine-, omega-3-, and RNA-enriched formulations significantly reduced infectious complications and hospital stay (70). Mechanistically, Calder et al. described how omega-3 fatty acids modulate inflammatory and pro-resolving mediators, contributing to improved microvascular repair and immune balance during recovery (71). Consistent with these findings, a prospective trial (ClinicalTrials.gov identifier NCT05028101) is currently investigating the effect of arginine-based immunonutrition in patients undergoing autologous breast reconstruction with free flaps (72).

Collectively, the ongoing prospective trials exploring perioperative antioxidant and immunonutritional strategies highlight the growing recognition of redox and metabolic modulation as emerging therapeutic adjuncts in microsurgical reconstruction. These interventions—ranging from glutathione and vitamin C to arginine- and omega-3-enriched formulations—share convergent mechanisms aimed at preserving endothelial integrity, enhancing microvascular perfusion, and optimizing postoperative recovery. Further high-quality studies will be essential to define their precise clinical indications and integration into standardized perioperative care pathways for autologous breast reconstruction.

Protein optimization and nutritional risk stratification

Adequate perioperative protein status is a key determinant of wound healing, immune competence, and microvascular stability across major surgical procedures (73-77). In the specific context of autologous reconstruction with free flaps, these processes are particularly relevant, as tissue viability and healing depend heavily on the preservation of microvascular integrity and protein-mediated repair mechanisms (75-78). Major reconstructive procedures elicit a catabolic stress response characterized by increased proteolysis, hepatic acute-phase activation, and a decline in plasma protein synthesis (73-75). When uncorrected, this imbalance compromises collagen deposition, fibroblast proliferation, and angiogenesis, thereby delaying wound healing and predisposing to microvascular complications (76-78). These physiological mechanisms underscore the importance of perioperative protein optimization as a modifiable factor influencing reconstructive outcomes (74-77).

Malnutrition—often reflected by low serum albumin or prealbumin levels—has been consistently associated with adverse surgical outcomes. In a retrospective cohort of patients undergoing head and neck free-flap reconstruction, Shum et al. found that low prealbumin levels increased the risk of flap failure fourfold (78). Similarly, Chiang et al., analyzing over 10,000 cases of autologous breast reconstruction, demonstrated that hypoalbuminemia (<3.5 g/dL) was independently associated with higher wound-complication rates and prolonged hospitalization, particularly when combined with obesity—a condition that itself increases inflammatory and metabolic stress (79). In parallel, Knoedler et al. analyzed over 7,000 cases of breast reduction surgery and reported that preoperative hypoalbuminemia (<3.5 g/dL) nearly doubled the risk of postoperative complications at 30 days, reinforcing the predictive role of protein status in breast surgery (80). In line with these findings, Guo et al. showed in a prospective cohort of 96 patients with oral and maxillofacial malignancy that preoperative malnutrition and postoperative protein depletion were significantly correlated with higher complication rates (56% vs. 20%, P<0.001), underscoring the pivotal role of perioperative nutritional management in complex reconstructive surgery (81). In autologous breast reconstruction, these findings highlight the potential value of targeted preoperative protein optimization when albumin is <3.5 g/dL or when recent weight loss or reduced intake is identified, as both conditions are associated with higher wound morbidity (79,80,82).

Even in patients without overt malnutrition, preoperative protein-energy supplementation has demonstrated measurable benefits. In a randomized controlled trial, Kabata et al. showed that two weeks of preoperative oral nutritional support significantly reduced postoperative complications and prevented declines in serum albumin and transferrin levels in nonmalnourished cancer patients (83). Similarly, Moya et al. and Perrone et al. reported that perioperative nutritional support—particularly with protein- and immunonutrient-enriched formulas—reduced inflammatory markers, insulin resistance, and postoperative morbidity (84,85). These findings justify a short preoperative window for protein-focused prehabilitation when feasible, particularly before extensive autologous reconstruction.

Evidence from large meta-analyses supports the relevance of structured preoperative nutritional therapy in major surgery. In a comprehensive 2024 Cochrane review including 16 randomized controlled trials and 2,164 participants undergoing gastrointestinal surgery, Sowerbutts et al. reported that preoperative oral or enteral nutrition supplementation did not significantly alter overall complication rates but probably reduced postoperative infections among malnourished or weight-losing patients (RR 0.53; 95% CI: 0.37–0.77) (86). Although the certainty of evidence was rated low to very low, these findings underscore the potential benefit of nutritional optimization in metabolically vulnerable populations and reinforce the rationale for targeted protein support before extensive reconstructive procedures. The authors also noted that, despite a strong physiological rationale, preoperative nutritional interventions remain inconsistently implemented within ERAS frameworks—underscoring a translational gap that is likewise evident in reconstructive microsurgery.

Given these findings, identifying and optimizing high-risk profiles through early nutritional screening is essential to improve reconstructive outcomes. Validated tools such as the NRS-2002, SGA, or PONS, in combination with biochemical markers (albumin, prealbumin, Prognostic Nutritional Index, or Controlling Nutritional Status score), enable early detection of protein malnutrition and support individualized perioperative nutritional strategies (75,87). Because of its short half-life (2–3 days), prealbumin provides a sensitive marker of acute protein status and has demonstrated prognostic value in free-flap surgery, supporting its use for dynamic monitoring of perioperative nutritional interventions (78). Embedding these tools within a structured prehabilitation workflow facilitates timely referral to nutrition services and measurable targets for perioperative protein delivery (74,75). Moreover, recent large-scale risk models demonstrate that integrating hypoalbuminemia and frailty indices (mFI-5 + albumin) enhances prognostic accuracy in free-flap surgery, providing a pragmatic framework to identify candidates for targeted protein prehabilitation (88,89).

Although perioperative protein supplementation and early oral feeding are now recognized as integral components of ERAS protocols in gastrointestinal and oncologic surgery, their systematic application in reconstructive microsurgery remains limited (75,88). Current American Society for Enhanced Recovery/Perioperative Quality Initiative consensus statements further emphasize that protein intake, rather than total caloric delivery, represents a key modifiable determinant of surgical outcome (90). Nonetheless, most of the supporting evidence arises from abdominal and oncologic surgery, with few data directly addressing free-flap or autologous breast reconstruction. Within this context, structured perioperative protein optimization may be regarded as an emerging, evidence-based metabolic strategy extrapolated from gastrointestinal and oncologic surgery, supported by robust physiological rationale and clinical data, to enhance tissue repair, reduce complications, and improve recovery in microsurgical breast reconstruction (74,75,88,90).

This paradigm is further reinforced by the American Society of Anesthesiologists (ASA), whose updated fasting guidelines now permit clear liquids containing carbohydrates or protein up to two hours before anesthesia, acknowledging the benefits of perioperative metabolic continuity (91). Together, these guidelines and clinical findings converge toward a more proactive approach to perioperative nutrition, reframing it as a core therapeutic intervention rather than a supportive measure.

Recent reviews have emphasized that perioperative protein optimization should be approached as a modifiable risk factor comparable to glycemic control, advocating for individualized prehabilitation plans combining nutritional supplementation, exercise, and metabolic optimization (74,87,89). Biomarkers with shorter half-lives, such as prealbumin, offer a dynamic means of monitoring response to nutritional therapy, while combining prealbumin or albumin levels with frailty indices has been shown to improve risk prediction across large surgical datasets (78,89). Together, these findings highlight that perioperative protein optimization is a critical and actionable component of metabolic prehabilitation in microsurgical breast reconstruction. Structured assessment, early intervention, and integration of protein-rich or immunonutrient-enriched formulas may substantially improve wound healing, reduce complications, and enhance flap survival.

Carbohydrate loading and perioperative insulin resistance

Surgical stress induces a cascade of endocrine and inflammatory responses that collectively promote insulin resistance, hyperglycemia, and accelerated protein catabolism. This metabolic response—mediated by elevated cortisol, catecholamines, and pro-inflammatory cytokines—leads to impaired glucose uptake, negative nitrogen balance, and delayed wound healing (92). These mechanisms are particularly relevant in autologous reconstruction with free flaps, where metabolic stability directly influences tissue perfusion, cellular repair, and microvascular integrity.

Preoperative carbohydrate loading—the administration of carbohydrate-rich clear liquids approximately two to three hours before anesthesia—has emerged as an effective and physiologically sound strategy to attenuate postoperative insulin resistance and enhance metabolic recovery. A series of randomized controlled trials and meta-analyses in gastrointestinal and oncologic surgery have consistently demonstrated that carbohydrate loading reduces postoperative insulin resistance, preserves lean body mass, improves patient comfort, and shortens hospital stay compared with overnight fasting, without increasing the risk of aspiration (93-98).

In one of the earliest meta-analyses, Awad et al. reported that preoperative oral carbohydrate treatment significantly decreased postoperative insulin resistance and improved patient well-being, confirming the safety of this approach in elective surgery (93). Hausel et al. further demonstrated that patients who received a carbohydrate-rich drink experienced less thirst, hunger, and anxiety, and achieved earlier mobilization compared with those who fasted conventionally (94). Similarly, Yuill et al. demonstrated that preoperative oral carbohydrate administration preserved postoperative skeletal muscle mass, supporting previous evidence of improved insulin sensitivity and metabolic response following carbohydrate loading before major abdominal surgery (95). A network meta-analysis by Amer et al., including over 3,000 patients, found that clear liquids containing 50–100 g of carbohydrates given two to three hours before anesthesia modestly reduced postoperative hospital stay compared with fasting, but showed no additional benefit compared with water or placebo (96). The large PROCY phase III trial by Gianotti et al. corroborated these findings, demonstrating better glycemic control with reduced perioperative insulin requirements, although infection rates were unchanged (97). More recently, a Bayesian network meta-analysis confirmed that this intervention enhances insulin sensitivity and postoperative recovery across diverse surgical settings (98).

The importance of maintaining metabolic continuity in the perioperative period is underscored by recent systematic evidence. The 2024 Cochrane review on preoperative nutrition therapy highlighted that, although ERAS pathways increasingly incorporate protein- and carbohydrate-rich nutrition, consensus on standardized prehospital interventions remains limited and the certainty of evidence is low to moderate (86).

Building on this evidence, the 2021 ESPEN Clinical Nutrition in Surgery Guidelines designate preoperative carbohydrate loading as a core component of ERAS pathways, recommending the ingestion of clear carbohydrate-containing drinks (45–100 g) up to two hours before anesthesia to mitigate insulin resistance and enhance postoperative recovery (75). Likewise, the 2023 ASA Practice Guidelines for Preoperative Fasting explicitly recommend the ingestion of carbohydrate-containing clear liquids up to two hours before anesthesia, reaffirming the safety of this approach and reflecting the paradigm shift from traditional fasting toward metabolic prehabilitation (91).

Although carbohydrate loading is well established in abdominal and oncologic surgery, its specific application in reconstructive microsurgery remains largely unexplored. To date, no randomized studies have directly evaluated the impact of preoperative carbohydrate intake on outcomes in free-flap or autologous breast reconstruction. Nonetheless, its physiological rationale and demonstrated safety in other high-stress surgical models justify its extrapolation to this field.

Emerging ERAS protocols for breast reconstruction have incorporated preoperative carbohydrate drinks, shortened fasting, and early postoperative feeding as core components. Both the ERAS Society consensus for breast reconstruction (Temple-Oberle et al.) and the prospective cohort by Astanehe et al. demonstrated that these interventions reduce hospital stay by approximately two days, decrease opioid consumption, and do not increase flap-related complications (17,99). Such findings reinforce that carbohydrate loading, though long validated in other surgical contexts, remains a novel and physiologically grounded component within reconstructive microsurgery—one that aligns with the broader movement toward perioperative metabolic optimization and individualized prehabilitation.

Drain management and prevention of seroma, hematoma, and surgical-site infection

Closed-suction drains play an essential role in autologous breast reconstruction, helping to prevent fluid accumulation, seroma formation, and excessive tension over microsurgical anastomoses (100). Nevertheless, their presence also introduces a potential route for retrograde bacterial migration and subsequent surgical site-infection (SSI) (101,102). The balance between adequate drainage and timely removal has therefore become a critical element of perioperative optimization.

Evidence from both reconstructive and general surgical fields supports that early drain removal—either at discharge or once the 24-hour output has remained consistently low, typically between 20 and 50 mL—does not increase the risk of SSI and is associated with shorter hospitalization and improved patient comfort (103-105). However, meta-analytic data indicate a modest increase in seroma rates with very early removal, suggesting that drainage protocols should be individualized according to output trends, flap characteristics, and patient factors (104,106).

In autologous breast reconstruction, particularly DIEP flaps, the number and position of drains vary widely among institutions. Recent studies have questioned the necessity of multiple drains, proposing simplified or even drain-free protocols without increased postoperative morbidity (107-109). A recent retrospective study (110) compared data of 204 patients who received traditional donor site closure with 188 patients who received progressive tension sutures with or without drain placement. The incidence of seroma formation was lower in the progressive tension suture group compared with that in the traditional closure and drain placement group. Aesthetic outcome was perceived more pleasing objectively and subjectively if progressive tension sutures were performed. Regarding patient satisfaction (BREAST-Q), no difference was found in the postoperative physical well-being between the two groups.

Given the biomechanical similarities between the DIEP donor site and abdominoplasty incisions, evidence from the abdominoplasty literature provides important contextual information when interpreting drain-free or modified closure strategies. In a large cohort of massive–weight-loss abdominoplasty patients, Marchica et al. reported that the use of progressive tension (quilting) sutures and fibrin glue was not associated with a reduction in seroma formation or other wound complications (111). These findings are consistent with meta-analytic evidence highlighting heterogeneity across techniques. A meta-analysis by Ardehali and Fiorentino demonstrated variable effects of abdominoplasty modifications on seroma outcomes, with progressive tension sutures and Scarpa’s fascia preservation showing potential benefit in some studies, while fibrin glue did not confer a consistent advantage (112). Similarly, Ho et al. found no significant differences in rates of individual complications—including seroma and hematoma—across combinations of drains, progressive tension sutures, and sub-Scarpa preservation, underscoring variability in study design, surgical technique, and outcome definitions (113). Together, these data support cautious extrapolation of abdominoplasty-derived strategies to DIEP donor-site closure and favor individualized decision-making rather than routine adoption of drain-free protocols.

Retrograde contamination of drainage systems remains a recognized concern. Multiple studies have identified bacterial colonization of drain fluid as a potential source of SSI, especially in prosthetic or expander-based reconstruction (101,114,115). Randomized trials evaluating antiseptic drain care—including the use of chlorhexidine-coated dressings and antiseptic instillation—have demonstrated a significant reduction in bacterial colonization, though without consistent effects on infection rates (116-118). The application of Dakin’s solution (sodium hypochlorite) has also been proposed for drain antisepsis, given its broad antimicrobial spectrum and historical safety profile in wound management (119,120).

Institutional drain care protocols emphasizing meticulous handling, closed-system integrity, and daily disinfection of drain exit sites have been shown to reduce infection rates in expander-based reconstruction and may be extrapolated to autologous settings (108,121). In addition, recent perioperative optimization frameworks emphasize the alignment of drain management with antibiotic stewardship, as prolonged prophylaxis beyond 24 hours does not appear to reduce infection risk following autologous reconstruction (122-125).

Overall, optimal drain management remains a dynamic field. Early removal—guided by objective drainage thresholds and clinical assessment—combined with standardized antiseptic care and evidence-based antibiotic use, represents an emerging perioperative strategy to reduce complications and support recovery in patients undergoing autologous breast reconstruction. While some principles of drain management are already reflected in ERAS recommendations for breast reconstruction (100–106), many of the strategies discussed here—such as drain antisepsis protocols and drain-free concepts—are still emerging elements within broader perioperative optimization efforts (107–125).

Discussion

Perioperative optimization in autologous breast reconstruction has traditionally focused on standardized pathways for anesthesia, analgesia, mobilization, and nutrition. More recently, increasing attention has been directed toward complementary strategies that target the biological and metabolic determinants of healing—areas such as oxygenation, redox modulation, nutritional status, and wound management. While these interventions have shown encouraging results across various surgical settings, their specific role in microsurgical breast reconstruction remains only partially defined.

The measures reviewed in this article—including HBOT, ciNPWT, antioxidant and metabolic modulation, targeted nutritional support, and structured drain management—share the common aim of supporting microvascular stability, reducing postoperative complications, and enhancing recovery. Together, they represent a gradual evolution from protocol-based perioperative care toward a more comprehensive and individualized approach, where systemic and local factors are considered in concert. This perspective underscores the importance of patient selection, early nutritional screening, and coordinated multidisciplinary care rather than isolated technical refinements.

Although the current evidence base is promising, most studies remain limited by retrospective design, small sample sizes, and heterogeneous outcome reporting. Accordingly, the strength of evidence supporting the perioperative interventions discussed in this review is heterogeneous, ranging from relatively robust clinical data to approaches primarily supported by physiological rationale or extrapolated findings (summarized in Table 2).

Protocol heterogeneity across studies—including differences in patient populations, perioperative interventions, timing, and outcome definitions—limits direct comparability and may partially explain variability in reported effects across emerging therapies. Small sample sizes further limit statistical power and the reliability of observed associations, while retrospective designs inherently restrict causal inference and increase the risk of selection and reporting bias. Future research should aim to standardize protocols, include objective physiological and patient-reported endpoints, and evaluate cost-effectiveness within structured recovery programs. Collaborative multicenter efforts will be key to validating these emerging interventions and translating them into reproducible clinical benefit. As a narrative review, this article may also be subject to selection bias despite efforts to include clinically relevant and representative studies.

Conclusions

In conclusion, optimizing perioperative care in autologous breast reconstruction requires an integrated strategy that bridges surgical precision with systemic support. The convergence of surgical, anesthetic, and metabolic insights offers an opportunity to refine recovery, minimize morbidity, and advance toward a model of integrated, patient-centered perioperative optimization.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-539/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-539/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-539/coif). All authors are affiliated with Affidea Plastic Surgery Group, a for-profit organization. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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References

1. Scaglioni MF, Martini F, Meroni M. Present and Future of Autologous Breast Reconstruction: Advancing Techniques to Minimize Morbidity and Complications, Enhancing Quality of Life and Patient Satisfaction. J Clin Med 2025;14:2599. [Crossref] [PubMed]
2. Speck NE, Grufman V, Farhadi J. Trends and Innovations in Autologous Breast Reconstruction. Arch Plast Surg 2023;50:240-7. [Crossref] [PubMed]
3. DeVito RG, Craft L, Campbell CA, et al. Optimizing perioperative outcomes in autologous breast reconstruction. Gland Surg 2023;12:508-15. [Crossref] [PubMed]
4. Allen RJ, Treece P. Deep inferior epigastric perforator flap for breast reconstruction. Ann Plast Surg 1994;32:32-8. [Crossref] [PubMed]
5. Blondeel PN, Van Landuyt KH, Monstrey SJ, et al. The "Gent" consensus on perforator flap terminology: preliminary definitions. Plast Reconstr Surg 2003;112:1378-87. [Crossref] [PubMed]
6. Nahabedian MY, Facs MD. Innovations and advancements in breast reconstruction. Gland Surg 2015;4:91-2. [Crossref] [PubMed]
7. Batdorf NJ, Lemaine V, Lovely JK, et al. Enhanced recovery after surgery in microvascular breast reconstruction. J Plast Reconstr Aesthet Surg 2015;68:395-402. [Crossref] [PubMed]
8. Kaoutzanis C, Ganesh Kumar N, O'Neill D, et al. Enhanced Recovery Pathway in Microvascular Autologous Tissue-Based Breast Reconstruction: Should It Become the Standard of Care? Plast Reconstr Surg 2018;141:841-51. [Crossref] [PubMed]
9. Sebai ME, Siotos C, Payne RM, et al. Enhanced Recovery after Surgery Pathway for Microsurgical Breast Reconstruction: A Systematic Review and Meta-Analysis. Plast Reconstr Surg 2019;143:655-66. [Crossref] [PubMed]
10. Soteropulos CE, Tang SYQ, Poore SO. Enhanced Recovery after Surgery in Breast Reconstruction: A Systematic Review. J Reconstr Microsurg 2019;35:695-704. [Crossref] [PubMed]
11. Bian HZ, Liau MYQ, Cheong GPC, et al. Enhanced recovery after surgery for breast reconstruction—a systematic review and meta-analysis. Ann Breast Surg 2024;8:26.
12. Weimann A, Braga M, Carli F, et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr 2017;36:623-50. [Crossref] [PubMed]
13. Vollbracht C, Schneider B, Leendert V, et al. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo 2011;25:983-90.
14. Alexander JW, Supp DM. Role of Arginine and Omega-3 Fatty Acids in Wound Healing and Infection. Adv Wound Care (New Rochelle) 2014;3:682-90. [Crossref] [PubMed]
15. Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg 2017;152:292-8. [Crossref] [PubMed]
16. Fearon KC, Ljungqvist O, Von Meyenfeldt M, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr 2005;24:466-77. [Crossref] [PubMed]
17. Temple-Oberle C, Shea-Budgell MA, Tan M, et al. Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations. Plast Reconstr Surg 2017;139:1056e-71e. [Crossref] [PubMed]
18. Thom SR. Oxidative stress is fundamental to hyperbaric oxygen therapy. J Appl Physiol (1985) 2009;106:988-95. [Crossref] [PubMed]
19. Kindwall EP, Whelan HT. Hyperbaric medicine practice. 3rd ed. Flagstaff (AZ): Best Publishing; 2008.
20. Godman CA, Joshi R, Giardina C, et al. Hyperbaric oxygen treatment induces antioxidant gene expression. Ann N Y Acad Sci 2010;1197:178-83. [Crossref] [PubMed]
21. André-Lévigne D, Modarressi A, Pignel R, et al. Hyperbaric oxygen therapy promotes wound repair in ischemic and hyperglycemic conditions, increasing tissue perfusion and collagen deposition. Wound Repair Regen 2016;24:954-65. [Crossref] [PubMed]
22. Nemiroff PM, Merwin GE, Brant T, et al. Effects of hyperbaric oxygen and irradiation on experimental skin flaps in rats. Otolaryngol Head Neck Surg 1985;93:485-91. [Crossref] [PubMed]
23. Marx RE, Ehler WJ, Tayapongsak P, et al. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surg 1990;160:519-24. [Crossref] [PubMed]
24. Moen I, Stuhr LE. Hyperbaric oxygen therapy and cancer--a review. Target Oncol 2012;7:233-42. [Crossref] [PubMed]
25. Carl UM, Feldmeier JJ, Schmitt G, et al. Hyperbaric oxygen therapy for late sequelae in women receiving radiation after breast-conserving surgery. Int J Radiat Oncol Biol Phys 2001;49:1029-31. [Crossref] [PubMed]
26. Pandey K, Teguh DN, van Hulst RA. Effect of hyperbaric oxygen treatment on skin elasticity in irradiated patients. Diving Hyperb Med 2022;52:208-12. [Crossref] [PubMed]
27. Batenburg MCT, Maarse W, van der Leij F, et al. The impact of hyperbaric oxygen therapy on late radiation toxicity and quality of life in breast cancer patients. Breast Cancer Res Treat 2021;189:425-33. [Crossref] [PubMed]
28. Bennett MH, Feldmeier J, Hampson NB, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev 2016;4:CD005005. [Crossref] [PubMed]
29. Scampa M, Martineau J, Boet S, et al. Hyperbaric oxygen therapy outcomes in post-irradiated patient undergoing microvascular breast reconstruction: A preliminary retrospective comparative study. JPRAS Open 2024;42:1-9. [Crossref] [PubMed]
30. Meier EL, Hummelink S, Lansdorp N, et al. Perioperative hyperbaric oxygen treatment and postoperative complications following secondary breast reconstruction after radiotherapy: a case-control study of 45 patients. Diving Hyperb Med 2021;51:288-94. [Crossref] [PubMed]
31. Idris OA, Ahmedfiqi YO, Shebrain A, et al. Hyperbaric Oxygen Therapy for Complications in Nipple-Sparing Mastectomy with Breast Reconstruction: A Systematic Review. J Clin Med 2024;13:3535. [Crossref] [PubMed]
32. Francis A, Baynosa RC. Hyperbaric Oxygen Therapy for the Compromised Graft or Flap. Adv Wound Care (New Rochelle) 2017;6:23-32. [Crossref] [PubMed]
33. Rajpal N, Walters ET, Elmarsafi T, et al. Use of hyperbaric oxygen therapy for tissue ischemia after breast reconstruction. Undersea Hyperb Med 2019;46:461-5.
34. Spruijt NE, Hoekstra LT, Wilmink J, et al. Hyperbaric oxygen treatment for mastectomy flap ischaemia: A case series of 50 breasts. Diving Hyperb Med 2021;51:2-9. [Crossref] [PubMed]
35. Park SK, Schank KJ, Engwall-Gill A, et al. Superior gluteal artery perforator flap salvaged via hyperbaric oxygen therapy. BMJ Case Rep 2022;15:e248411. [Crossref] [PubMed]
36. Daniel A, Haney V, Tveit M, et al. Evaluating the effect of hyperbaric oxygen therapy to treat mastectomy skin flap ischemia in breast reconstruction: A single-institution retrospective analysis. Am J Surg 2025;242:116110. [Crossref] [PubMed]
37. Peterson DE, Koyfman SA, Yarom N, et al. Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline. J Clin Oncol 2024;42:1975-96. [Crossref] [PubMed]
38. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg 1997;38:563-76; discussion 577.
39. Kostaras EK, Tansarli GS, Falagas ME. Use of negative-pressure wound therapy in breast tissues: evaluation of the literature. Surg Infect (Larchmt) 2014;15:679-85. [Crossref] [PubMed]
40. Thompson JT, Marks MW. Negative pressure wound therapy. Clin Plast Surg 2007;34:673-84. [Crossref] [PubMed]
41. Willy C, Agarwal A, Andersen CA, et al. Closed incision negative pressure therapy: international multidisciplinary consensus recommendations. Int Wound J 2017;14:385-98. [Crossref] [PubMed]
42. Wells CI, Ratnayake CBB, Perrin J, et al. Prophylactic Negative Pressure Wound Therapy in Closed Abdominal Incisions: A Meta-analysis of Randomised Controlled Trials. World J Surg 2019;43:2779-88. [Crossref] [PubMed]
43. Kim DY, Park SJ, Bang SI, et al. Does the Use of Incisional Negative-Pressure Wound Therapy Prevent Mastectomy Flap Necrosis in Immediate Expander-Based Breast Reconstruction? Plast Reconstr Surg 2016;138:558-66. [Crossref] [PubMed]
44. Vidya R, Khosla M, Baek K, et al. Prophylactic Use of Negative Pressure Wound Therapy in High-risk Patients Undergoing Oncoplastic and Reconstructive Breast Surgery. Plast Reconstr Surg Glob Open 2023;11:e5488. [Crossref] [PubMed]
45. Gabriel A, Maxwell GP. Economic Analysis Based on the Use of Closed-Incision Negative-Pressure Therapy after Postoperative Breast Reconstruction. Plast Reconstr Surg 2019;143:36S-40S. [Crossref] [PubMed]
46. Gabriel A, Sigalove S, Sigalove N, et al. The Impact of Closed Incision Negative Pressure Therapy on Postoperative Breast Reconstruction Outcomes. Plast Reconstr Surg Glob Open 2018;6:e1880. [Crossref] [PubMed]
47. Singh DP, Gabriel A, Silverman R, et al. Meta-Analysis Comparing Outcomes of Two Different Closed Incision Negative Pressure Systems in Breast Surgery and Implications to Cost of Care. Eplasty 2024;24:e40.
48. Larsen AK, Hyldig N, Möller S, et al. Incisional negative pressure wound therapy on mastectomy skin flaps—does it reduce seroma formation? A prospective, randomized study. Ann Breast Surg 2020;4:5.
49. Dunson B, Kogan S, Grosser JA, et al. Influence of Closed-incision Negative Pressure Wound Therapy on Abdominal Site Complications in Autologous Breast Reconstruction. Plast Reconstr Surg Glob Open 2023;11:e5326. [Crossref] [PubMed]
50. Abul A, Abel A, Al-Saffar M, et al. Efficacy of closed-incision negative pressure wound therapy in abdominal-based autologous breast reconstruction: A systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2025;107:151-61. [Crossref] [PubMed]
51. Escobar-Domingo MJ, Bustos VP, Mahmoud AA, et al. Impact of closed-incision negative pressure therapy in donor-site complications in DIEP flap breast reconstruction: Analysis of 705 patients and 1125 flaps. J Plast Reconstr Aesthet Surg 2025;105:177-84. [Crossref] [PubMed]
52. Haas E, Garoosi K, Kalia N, et al. Complications associated with abdominal incisional wound vacuum assisted closure following deep inferior epigastric perforator flap harvest for breast reconstruction: A single institution retrospective study. J Plast Reconstr Aesthet Surg 2025;103:345-50. [Crossref] [PubMed]
53. Doval AF, Chegireddy V, Beal L, et al. Efficacy of Closed Incision Negative Pressure Wound Therapy on Abdominal Donor Site After Free Flap Breast Reconstruction. Wounds 2021;33:81-5.
54. Kang S, Okumura S, Maruyama Y, et al. Effect of Incision Negative Pressure Wound Therapy on Donor Site Morbidity in Breast Reconstruction with Deep Inferior Epigastric Artery Perforator Flap. JPRAS Open 2022;34:73-81. [Crossref] [PubMed]
55. Fang CL, Changchien CH, Chen MS, et al. Closed incision negative pressure therapy following abdominoplasty after breast reconstruction with deep inferior epigastric perforator flaps. Int Wound J 2020;17:326-31. [Crossref] [PubMed]
56. Siegwart LC, Sieber L, Fischer S, et al. Influence of closed incision negative-pressure therapy on abdominal donor-site morbidity in microsurgical breast reconstruction. Microsurgery 2022;42:32-9. [Crossref] [PubMed]
57. Muller-Sloof E, de Laat E, Kenç O, et al. Closed-Incision Negative-Pressure Therapy Reduces Donor-Site Surgical Wound Dehiscence in DIEP Flap Breast Reconstructions: A Randomized Clinical Trial. Plast Reconstr Surg 2022;150:38S-47S. [Crossref] [PubMed]
58. Zhang M, Liu Q, Meng H, et al. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Signal Transduct Target Ther 2024;9:12. [Crossref] [PubMed]
59. van den Heuvel MG, Buurman WA, Bast A, et al. Review: Ischaemia-reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg 2009;62:721-6. [Crossref] [PubMed]
60. Arrivi A, Barillà F, Carnevale R, et al. Protective Biomolecular Mechanisms of Glutathione Sodium Salt in Ischemia-Reperfusion Injury in Patients with Acute Coronary Syndrome-ST-Elevation Myocardial Infarction. Cells 2022;11:3964. [Crossref] [PubMed]
61. Cheung PY, Wang W, Schulz R. Glutathione protects against myocardial ischemia-reperfusion injury by detoxifying peroxynitrite. J Mol Cell Cardiol 2000;32:1669-78. [Crossref] [PubMed]
62. Kuo YR, Wang FS, Jeng SF, et al. Nitrosoglutathione promotes flap survival via suppression of reperfusion injury-induced superoxide and inducible nitric oxide synthase induction. J Trauma 2004;57:1025-31. [Crossref] [PubMed]
63. Bechara N, Flood VM, Gunton JE. A Systematic Review on the Role of Vitamin C in Tissue Healing. Antioxidants (Basel) 2022;11:1605. [Crossref] [PubMed]
64. Tenório MCDS, Graciliano NG, Moura FA, et al. N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel) 2021;10:967. [Crossref] [PubMed]
65. Suter M, Bollen Pinto B, Belletti A, et al. Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: a systematic review and meta-analysis of randomised trials. Br J Anaesth 2022;128:664-78. [Crossref] [PubMed]
66. Rayman MP. Selenium and human health. Lancet 2012;379:1256-68. [Crossref] [PubMed]
67. University of Virginia (US). Effectiveness of IV vitamin C in reducing oxidative stress associated with free flap surgery. ClinicalTrials.gov [Internet]. 2025 [cited 2025 Oct 22]. Available online: https://clinicaltrials.gov/study/NCT05327348
68. Booi DI, Debats IBJG, Deutz NEP, et al. Arginine improves microcirculation in the free transverse rectus abdominis myocutaneous flap after breast reconstruction: a randomized, double-blind clinical trial. Plast Reconstr Surg 2011;127:2216-23. [Crossref] [PubMed]
69. Wilhelm SM, Kale-Pradhan PB. Combination of arginine and omega-3 fatty acids enteral nutrition in critically ill and surgical patients: a meta-analysis. Expert Rev Clin Pharmacol 2010;3:459-69. [Crossref] [PubMed]
70. Klek S, Szybinski P, Szczepanek K. Perioperative immunonutrition in surgical cancer patients: a summary of a decade of research. World J Surg 2014;38:803-12. [Crossref] [PubMed]
71. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?. Br J Clin Pharmacol 2013;75:645-62.
72. University Hospital of Basel (CH). Arginine-based immunonutrition in patients undergoing free flap reconstruction. ClinicalTrials.gov [Internet]. 2025 [cited 2025 Oct 22]. Available online: https://clinicaltrials.gov/study/NCT05028101
73. Hill GL. Implications of critical illness, injury, and sepsis on lean body mass and nutritional needs. Nutrition 1998;14:557-8. [Crossref] [PubMed]
74. Carli F, Scheede-Bergdahl C. Prehabilitation to enhance perioperative care. Anesthesiol Clin 2015;33:17-33. [Crossref] [PubMed]
75. Weimann A, Braga M, Carli F, et al. ESPEN practical guideline: Clinical nutrition in surgery. Clin Nutr 2021;40:4745-61. [Crossref] [PubMed]
76. Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty 2009;9:e9.
77. Stechmiller JK. Understanding the role of nutrition and wound healing. Nutr Clin Pract 2010;25:61-8. [Crossref] [PubMed]
78. Shum J, Markiewicz MR, Park E, et al. Low prealbumin level is a risk factor for microvascular free flap failure. J Oral Maxillofac Surg 2014;72:169-77. [Crossref] [PubMed]
79. Chiang SN, Finnan MJ, Skolnick GB, et al. Compound Effect of Hypoalbuminemia and Obesity on Complications after Autologous Breast Reconstruction. Plast Reconstr Surg 2023;152:227e-36e. [Crossref] [PubMed]
80. Knoedler S, Klimitz FJ, Diatta F, et al. Protein as a preoperative predictor - Impact of hypoalbuminemia on 30-day outcomes of breast reduction surgery. J Plast Reconstr Aesthet Surg 2025;100:144-52. [Crossref] [PubMed]
81. Guo CB, Ma DQ, Zhang KH, et al. Relation between nutritional state and postoperative complications in patients with oral and maxillofacial malignancy. Br J Oral Maxillofac Surg 2007;45:467-70. [Crossref] [PubMed]
82. Xu H, Han Z, Ma W, et al. Perioperative Albumin Supplementation is Associated With Decreased Risk of Complications Following Microvascular Head and Neck Reconstruction. J Oral Maxillofac Surg 2021;79:2155-61. [Crossref] [PubMed]
83. Kabata P, Jastrzębski T, Kąkol M, et al. Preoperative nutritional support in cancer patients with no clinical signs of malnutrition--prospective randomized controlled trial. Support Care Cancer 2015;23:365-70. [Crossref] [PubMed]
84. Moya P, Soriano-Irigaray L, Ramirez JM, et al. Perioperative Standard Oral Nutrition Supplements Versus Immunonutrition in Patients Undergoing Colorectal Resection in an Enhanced Recovery (ERAS) Protocol: A Multicenter Randomized Clinical Trial (SONVI Study). Medicine (Baltimore) 2016;95:e3704. [Crossref] [PubMed]
85. Perrone F, da-Silva-Filho AC, Adôrno IF, et al. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial. Nutr J 2011;10:66. [Crossref] [PubMed]
86. Sowerbutts AM, Burden S, Sremanakova J, et al. Preoperative nutrition therapy in people undergoing gastrointestinal surgery. Cochrane Database Syst Rev 2024;4:CD008879. [Crossref] [PubMed]
87. Heutlinger O, Acharya N, Tedesco A, et al. Nutritional Optimization of the Surgical Patient: A Narrative Review. Adv Nutr 2025;16:100351. [Crossref] [PubMed]
88. Ricci C, Serbassi F, Alberici L, et al. Immunonutrition in patients who underwent major abdominal surgery: A comprehensive systematic review and component network metanalysis using GRADE and CINeMA approaches. Surgery. 2023;174:1401-9. [Crossref] [PubMed]
89. Panayi AC, Knoedler L, Matar DY, et al. The combined risk predictive power of frailty and hypoalbuminemia in free tissue flap reconstruction: A cohort study of 34,571 patients from the NSQIP database. Microsurgery 2024;44:e31156. [Crossref] [PubMed]
90. Wischmeyer PE, Carli F, Evans DC, et al. American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway. Anesth Analg 2018;126:1883-95. [Crossref] [PubMed]
91. Joshi GP, Abdelmalak BB, Weigel WA, et al. 2023 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting: Carbohydrate-containing Clear Liquids with or without Protein, Chewing Gum, and Pediatric Fasting Duration-A Modular Update of the 2017 American Society of Anesthesiologists Practice Guidelines for Preoperative Fasting. Anesthesiology 2023;138:132-51. [Crossref] [PubMed]
92. Thorell A, Nygren J, Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care 1999;2:69-78. [Crossref] [PubMed]
93. Awad S, Varadhan KK, Ljungqvist O, et al. A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery. Clin Nutr 2013;32:34-44. [Crossref] [PubMed]
94. Hausel J, Nygren J, Lagerkranser M, et al. A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients. Anesth Analg 2001;93:1344-50. [Crossref] [PubMed]
95. Yuill KA, Richardson RA, Davidson HI, et al. The administration of an oral carbohydrate-containing fluid prior to major elective upper-gastrointestinal surgery preserves skeletal muscle mass postoperatively--a randomised clinical trial. Clin Nutr 2005;24:32-7. [Crossref] [PubMed]
96. Amer MA, Smith MD, Herbison GP, et al. Network meta-analysis of the effect of preoperative carbohydrate loading on recovery after elective surgery. Br J Surg 2017;104:187-97. [Crossref] [PubMed]
97. Gianotti L, Biffi R, Sandini M, et al. Preoperative Oral Carbohydrate Load Versus Placebo in Major Elective Abdominal Surgery (PROCY): A Randomized, Placebo-controlled, Multicenter, Phase III Trial. Ann Surg 2018;267:623-30. [Crossref] [PubMed]
98. Tong E, Chen Y, Ren Y, et al. Effects of preoperative carbohydrate loading on recovery after elective surgery: A systematic review and Bayesian network meta-analysis of randomized controlled trials. Front Nutr 2022;9:951676. [Crossref] [PubMed]
99. Astanehe A, Temple-Oberle C, Nielsen M, et al. An Enhanced Recovery after Surgery Pathway for Microvascular Breast Reconstruction Is Safe and Effective. Plast Reconstr Surg Glob Open 2018;6:e1634. [Crossref] [PubMed]
100. Khansa I, Khansa L, Meyerson J, et al. Optimal Use of Surgical Drains: Evidence-Based Strategies. Plast Reconstr Surg 2018;141:1542-9. [Crossref] [PubMed]
101. Reiffel AJ, Barie PS, Spector JA. A multi-disciplinary review of the potential association between closed-suction drains and surgical site infection. Surg Infect (Larchmt) 2013;14:244-69. [Crossref] [PubMed]
102. Yoon J, Chung JH, Hwang NH, et al. Bacterial profile of suction drains and the relationship thereof to surgical-site infections in prosthetic breast reconstruction. Arch Plast Surg 2018;45:542-9. [Crossref] [PubMed]
103. Shima H, Kutomi G, Sato K, et al. An Optimal Timing for Removing a Drain After Breast Surgery: A Systematic Review and Meta-Analysis. J Surg Res 2021;267:267-73. [Crossref] [PubMed]
104. Vos H, Smeets A, Neven P, et al. Early drain removal improves quality of life and clinical outcomes in patients with breast cancer - Results from a randomised controlled trial. Eur J Oncol Nurs 2018;36:112-8. [Crossref] [PubMed]
105. Lim B, Seth I, Joseph K, et al. Optimal Use of Drain Tubes for DIEP Flap Breast Reconstruction: Comprehensive Review. J Clin Med 2024;13:6586. [Crossref] [PubMed]
106. Goto D, Oshima A, Onishi T, et al. Safety and efficacy of early drain removal in breast reconstruction: a retrospective cohort study. Breast Cancer 2026;33:217-26. [Crossref] [PubMed]
107. Evgeniou E, Liew J, Lee G, et al. Are Surgical Drains Needed in DIEP Flap Surgery? The Drain-Free DIEP Flap Concept. Plast Reconstr Surg 2023;152:708-14. [Crossref] [PubMed]
108. Miranda BH, Amin K, Chana JS. The drain game: abdominal drains for deep inferior epigastric perforator breast reconstruction. J Plast Reconstr Aesthet Surg 2014;67:946-50. [Crossref] [PubMed]
109. Kim J, Lee KT, Mun GH. Shifting toward total drainless approach in DIEP flap-based breast reconstruction: Evaluation of safety. J Plast Reconstr Aesthet Surg 2024;95:152-60. [Crossref] [PubMed]
110. Merchant AS, Speck NE, Lalji R, et al. Evaluating the benefit of progressive tension sutures at the donor site in autologous breast reconstruction - A retrospective comparative cohort study. J Plast Reconstr Aesthet Surg 2024;98:46-54. [Crossref] [PubMed]
111. Marchica P, Costa AL, Brambullo T, et al. Retrospective Analysis of Predictive Factors for Complications in Abdominoplasty in Massive Weight Loss Patients. Aesthetic Plast Surg 2023;47:1447-58. [Crossref] [PubMed]
112. Ardehali B, Fiorentino F. A Meta-Analysis of the Effects of Abdominoplasty Modifications on the Incidence of Postoperative Seroma. Aesthet Surg J 2017;37:1136-43. [Crossref] [PubMed]
113. Ho W, Jones CD, Pitt E, et al. Meta-analysis on the comparative efficacy of drains, progressive tension sutures and subscarpal fat preservation in reducing complications of abdominoplasty. J Plast Reconstr Aesthet Surg 2020;73:828-40. [Crossref] [PubMed]
114. Degnim AC, Scow JS, Hoskin TL, et al. Randomized controlled trial to reduce bacterial colonization of surgical drains after breast and axillary operations. Ann Surg 2013;258:240-7. [Crossref] [PubMed]
115. Degnim AC, Hoskin TL, Brahmbhatt RD, et al. Randomized trial of drain antisepsis after mastectomy and immediate prosthetic breast reconstruction. Ann Surg Oncol 2014;21:3240-8. [Crossref] [PubMed]
116. Rivera-Buendía F, Franco-Cendejas R, Román-López CG, et al. Randomized Controlled Trial to Reduce Bacterial Colonization of Surgical Drains with the Use of Chlorhexidine-Coated Dressings After Breast Cancer Surgery. Ann Surg Oncol 2019;26:3883-91. [Crossref] [PubMed]
117. Taha N, Rahman S, Kilshaw A. The Efficacy of Antiseptic Treatment of Surgical Drains on Bacterial Colonisation and Surgical Site Infection Post Breast Surgery: A Systematic Review and Meta-Analysis. Cureus 2023;15:e41585. [Crossref] [PubMed]
118. Scomacao I, Cummins A, Roan E, et al. The use of surgical site drains in breast reconstruction: A systematic review. J Plast Reconstr Aesthet Surg 2020;73:651-62. [Crossref] [PubMed]
119. Ueno CM, Mullens CL, Luh JH, et al. Historical review of Dakin's solution applications. J Plast Reconstr Aesthet Surg 2018;71:e49-e55. [Crossref] [PubMed]
120. Serena TE, Serena L, Al-Jalodi O, et al. The efficacy of sodium hypochlorite antiseptic: a double-blind, randomised controlled pilot study. J Wound Care 2022;31:S32-5. [Crossref] [PubMed]
121. Murray JD, Elwood ET, Jones GE, et al. Decreasing expander breast infection: A new drain care protocol. Can J Plast Surg 2009;17:17-21.
122. Warren DK, Nickel KB, Hostler CJ, et al. Surgeon choice in the use of postdischarge antibiotics for prophylaxis following mastectomy with and without breast reconstruction. Infect Control Hosp Epidemiol 2021;42:467-70. [Crossref] [PubMed]
123. Warren DK, Peacock KM, Nickel KB, et al. Postdischarge prophylactic antibiotics following mastectomy with and without breast reconstruction. Infect Control Hosp Epidemiol 2022;43:1382-8. [Crossref] [PubMed]
124. Rijkx MEP, Klein DO, Hommes JE, et al. Evidence for the use of peri- and post-operative antibiotic prophylaxis in autologous breast reconstruction: A systematic review. J Plast Reconstr Aesthet Surg 2023;83:404-14. [Crossref] [PubMed]
125. Liu DZ, Dubbins JA, Louie O, et al. Duration of antibiotics after microsurgical breast reconstruction does not change surgical infection rate. Plast Reconstr Surg 2012;129:362-7. [Crossref] [PubMed]