Applied Surgical, Pathologic, and Physiologic Concepts
General
The resection of tumors may cause large aesthetically and functionally unacceptable defects. Similarly, adjuvant therapies may leave functional tissue impairment or chronic nonhealing wounds requiring excision and reconstruction. Reconstructive surgery aims to obliterate dead space, provide structural support for remaining tissues, ensure adequate wound closure and healing, and maintain an aesthetically acceptable appearance.
Flap surgery has improved markedly over the last few decades, with success rates of greater than 95% reported. This is the result of enhanced microsurgical techniques and an evolving appreciation for perioperative optimization. In this setting of progress, however, anesthetic perioperative management of free flap surgery is varied, reflecting the paucity of high-level evidence guiding best practice. Continued critical review of current flap surgery literature and extrapolation from other surgical fields is imperative to improve outcomes.
Surgical Concepts
Autologous flap reconstructions can be categorized as “pedicled” or “free.” A pedicled flap remains partially connected to the donor site via an intact vascular pedicle. The pedicle is at most 5 cm long, limiting reconstruction to local defects. A latissimus dorsi flap, used in breast reconstruction, is a commonly used example. Free flaps are completely detached from the donor site and constitute any combination of skin, fat, fascia, muscle, bone, nerves, bowel, or omentum. These flaps are used for more distant reconstructions.
There are several distinct phases during free flap surgery. In the initial phase, donor tissue and its vascular pedicle (artery and vein) are dissected or raised . The clamping and division of the pedicle leads to cessation of blood flow to the donor tissue. This primary ischemic phase varies in duration but typically lasts between 60 and 90 min. Donor blood vessels are then anastomosed to distant recipient blood vessels using microsurgical techniques. Restoration of blood flow and reversal of the effects of anaerobic metabolism occur during this reperfusion phase . This phase, also called the secondary ischemic phase , is susceptible to ischemic reperfusion injury.
There is a single surgical anastomosis of each vascular pedicle, making free flaps extremely vulnerable to hypoperfusion and venous congestion. Common causes of impaired blood flow include arterial or venous thrombosis at the anastomotic site, arterial vasospasm, and insufficient venous drainage. Ruptured anastomosis with hematoma formation, tightly applied dressings, and poorly positioned equipment can cause external compression on the pedicle. Some vascular pedicles are prone to kinking or stretching with changes in patient positioning. Prolonged ischemic times and flap hypoperfusion secondary to low cardiac output states may exacerbate the secondary ischemic injury.
Pathologic Concepts Associated With Free Flap Complications: The Endothelial Glycocalyx, Inflammation, and Ischemic Reperfusion Injury
The endothelial glycocalyx (EG) is a gel-like structure, lining the intraluminal surface of the endothelial cells of all blood vessels and organs. It has several well-defined functions and plays an integral role in blood vessel wall integrity. It is a delicate structure and can rapidly change under certain metabolic and inflammatory conditions. Lifestyle risk factors (obesity, smoking), adjuvant treatments (radiotherapy), and chronic pathologic conditions (hyperglycemia, renal and cardiovascular disease) predisposes this delicate structure to pathologic insults. , Acute degradation of the EG has also been observed in patients undergoing major surgery, leading to capillary leak, platelet aggregation, and loss of vascular responsiveness. In the perioperative setting, this can result in tissue edema, detrimental to wound healing, acute kidney injury, increased risk of venous thromboembolism (VTE), and lability of arterial pressure.
Flap surgery has the potential to cause major systemic inflammatory perturbation in the postoperative period. Large, multisite tissue disruption, and ischemic reperfusion injury, seen within the flap microvasculature, can cause disruption to the composition and structure of the fragile EG. Degradation leads to loss of the barrier function between blood components and the underlying vessel wall. The adhesion of circulating immune cells and activation of several proinflammatory pathways cause further disruption and dysfunction within this layer. These pathologic processes may progress and lead to localized effects (flap complications, organ dysfunction) or systemic effects (systemic inflammatory response syndrome, coagulopathies). ,
Following ischemic reperfusion injury, deactivation of some of the protective antioxidative enzymes within the EG leads to oxidative stress. This includes the deactivation of superoxide, a natural antioxidant active within the EG, which keeps reactive oxygen species and free radicals in equilibrium under physiologic conditions. It also has a role in the functionality and release of other antioxidants such as nitric oxide. Nitric oxide causes localized vasodilation in response to increases in shear stress (increased blood flow). Therefore a reduction in its levels will result in loss of microvascular autoregulation, possibly compromising reperfusion.
In addition a degraded and exposed endothelium is vulnerable to platelet adhesion and activation of the coagulation cascade with subsequent thrombus propagation. As previously mentioned, venous and arterial thrombosis can be detrimental to flap viability. Venous thrombosis is more prevalent than arterial thrombosis.
Blood flow and oxygen delivery to free flap tissue may become impaired with a rise in local interstitial tissue pressure. Several factors predispose free flap tissues to this pathologic process.
In its physiologic state, the EG is a protein-rich layer that contributes significantly to intravascular oncotic pressure. According to the revised Starling equation, this oncotic pressure is an important factor opposing fluid filtration across the endothelial layer into the interstitium. With degradation and loss of the protein content of the EG, the layer becomes more permeable with increased filtration of fluid and other intravascular molecules into the interstitium. This is commonly seen in inflammatory states and contributes to a decrease in the half-life of intravenous (IV) crystalloids and colloids alike. , , Reabsorption of interstitial fluid relies exclusively on intact lymphatic flow and not on reabsorption from the venous capillaries, as previously stated by the original Starling equation. Transplanted free flap tissues are devoid of an intact lymphatic system and therefore vulnerable to any increase in fluid accumulation.
Perioperative fluid management is known to have a profound impact upon the integrity of the glycocalyx : acute hypervolemic hemodilution causes EG injury by mechanical stress on the vascular wall and via the secretion of atrial natriuretic peptide. This peptide is secreted in response to atrial stretch, which can be a consequence of rapidly infused IV fluid. It also increases microvascular permeability permitting fluid and colloid extravasation into the interstitium. Studies have shown that when 5% human albumin or 6% hydroxyethyl starch (HES) is infused into a normovolemic patient, 60% of the colloid rapidly extravasates into the interstitium.
The combination of the above-mentioned pathologic processes are likely reasons why multiple studies specific to flap surgery have linked high volumes of IV fluids with worse surgical (wound healing, flap failure) and medical (pulmonary congestion) outcomes.
Relevant to cancer surgery, the EG layer also acts as a barrier to prevent interaction between the ligands on circulating tumor cells and the adhesion receptors on endothelial cells. Following surgical tissue damage, inflammatory activation of procoagulant and prothrombotic pathways may cause clot formation in the microvasculature and platelet adhesion onto circulating tumor cells. This pathologic process has two consequences. The platelet coat on the circulating tumor cells decreases detection by host defense mechanisms such as natural killer cells. In addition, microvascular occlusion promotes adhesion of these cells onto the degraded endothelium, enabling migration across this layer. In effect, inflammatory mediators may contribute to colonization and lymphatic spread, promoting metastasis. ,
Hyperoxia causes increased levels of reactive oxygen species with increased tissue destruction after ischemic reperfusion injury. Studies looking at outcomes after ischemic events such as cerebral vascular accidents and myocardial infarction have linked hyperoxia with expansion of infarct size and worse outcomes. , Intraoperative inspired oxygen concentrations should be carefully titrated to the arterial partial pressure of oxygen (Pao 2 ) deemed appropriate for the clinical setting. Perioperative measures to improve pulmonary function should be employed to reduce the need for and duration of oxygen therapy.
In conclusion, seemingly safe routine perioperative therapies such as IV fluid and oxygen therapy can potentially cause harm by exacerbating the degradation of the EG seen during surgery. Possible strategies to reduce EG breakdown are discussed in the section on Strategies for Hemodynamic Optimization .
Physiology of Flap Perfusion and Relevant Perioperative Factors
The blood supply and drainage of free flap tissue can be complex. One cannot assume that an isolated understanding of the physiologic laws governing blood flow is sufficient. Instead, there is a dynamic and complex interplay between the pathologic and other physiologic processes requiring more complex consideration.
The Hagen-Poiseuille law is frequently used to describe the determinants of flap perfusion/flow:
Q = ∆Pπr 4 /8ηl
where Q (flow) is directly proportional to ∆P (perfusion pressure) and the fourth power of r (radius), and inversely proportional to η (viscosity) and l (length of the tube).
The radius of the blood vessels is an important determinant of blood flow but is not constant and homogeneous within the flap. This can be due to a number of independent factors. Irregularities in the endothelial layer close to the surgical anastomosis will invariably cause turbulence in blood flow and a decrease in the radius of the blood vessel. Reperfusion injury causes localized vasospasm, as well as shedding of the endothelial cells and glycocalyx with resultant microthrombus formation and propagation. Surgical manipulation and cold exposure of the vascular pedicle may also cause vasospasm. In addition, acute denervation of pedicle blood vessels causes an attenuated vasoconstrictor response to systemic catecholamines. As a result, normal physiologic laws do not hold true, and medical interventions aimed at altering the radius of the blood vessels might not reliably lead to improvements of blood flow.
The Hagen-Poiseuille law states that cardiac output is directly related to a pressure differential across a vascular bed. This is one of the reasons why routine intraoperative blood pressure (macrovascular) monitoring is used as a surrogate for tissue perfusion (microvascular). This has several limitations, as follows.
Cardiac output or blood flow is also dependent on systemic vascular resistance, as seen in the following equation:
Cardiac output = (mean arterial pressure – right atrial pressure)/systemic vascular resistance
An increase in peripheral resistance seen after the administration of a vasopressor agent may lead to an increase in blood pressure but a decrease in flow or cardiac output. This may compromise the free flap tissues. Additionally, the physiologic response to a hypovolemic state is to preserve perfusion pressure to vital organs at the expense of nonvital organs (skin and fat in the free flap). As a consequence, a predetermined target blood pressure may not reflect adequate flap perfusion and may be falsely reassuring.
Under physiologic conditions, there is an expectation that microvascular perfusion will improve in parallel with macrovascular optimization. This is referred to as hemodynamic coherence. Loss of hemodynamic coherence has been described in states of infection, inflammation, and reperfusion injury. The resultant impaired function of the endothelium and the EG leads to microvascular obstruction, vasoconstriction, and interstitial edema, despite correction of the macrovascular parameters. Regardless, optimization of the macrovascular parameters should be primarily achieved prior to targeting the microcirculation.
Noninvasive, intraoperative optical techniques may be used in real time to assess the microcirculation of free flap tissue. Novel techniques under investigation include optical coherence tomography (vessel density and decorrelation), side-stream darkfield microscopy (velocity, microvascular flow index, total vessel density, perfused vessel density), laser speckle contrast imaging (perfusion units), and fluorescence imaging (time constant and time to peak measured). Once integrated into standard practice, these bedside measurements may allow for dynamic assessment of medical interventions to optimize macrovascular parameters and flap tissue perfusion.
Strategies for Hemodynamic Optimization
Surgical intervention leads to an increase in oxygen consumption and metabolic demand. The aim of hemodynamic optimization is to reduce tissue hypoperfusion and meet the increased metabolic demands of the tissues. These measures should be instituted in the early preoperative period and may be continued postoperatively to overcome potential oxygen debt.
Preoperative Carbohydrate Drinks
Adequate preoperative hydration starts with minimization of fasting times. Complex carbohydrate drinks up to 2 h prior to surgery are safe and improve metabolism, and decrease insulin resistance and postoperative nausea and vomiting (PONV). Postoperatively, early transition to oral hydration should be encouraged, and IV fluids should be discontinued once the patient is hemodynamically stable.
Goal-Directed Therapy
Perioperative administration of IV fluid plays a pivotal role in patient management and has a direct impact on outcomes. The principles of IV fluid administration are to maintain central normovolemia for optimal cellular perfusion and to avoid interstitial edema from salt and water excess. The utilization of goal-directed therapy (GDT) allows for tailored IV fluid, inotropic, and vasoactive agent administration. Contemporary minimally invasive devices derive measurements such as cardiac index, stroke volume, or stroke volume variation from pulse power analysis, pulse contour analysis, and esophageal Doppler monitoring. Medical therapy is titrated according to these explicit targets that reflect end-organ blood flow.
Although a large number of randomized trials have been conducted investigating the effect of GDT on perioperative outcomes, concerns exist regarding the quality of studies, with the majority being single-center trials with methodological limitations and risk of bias. A systematic review and meta-analysis of 31 studies carried out by the Cochrane group in 2013 found no difference in mortality between patients receiving GDT compared with controls, but reported a significant reduction in overall complication rate and a reduced rate of renal and respiratory failure, wound infection, and length of hospital stay (LOHS). Two multicenter studies with larger participant numbers investigating the effects of GDT have been published since this review. , Addition of the OPTIMISE study, a multicenter randomized trial of high-risk patients undergoing major gastrointestinal surgery, to the original meta-analysis confirmed an overall reduction in complication rates across trials when GDT was utilized. These findings were reproduced in the FEDORA trial, where patients were randomized to GDT with optimization of circulating volume prior to vasopressor use versus standard care : significantly fewer complications were observed in the GDT group, and again a reduction in LOHS was observed. Finally, a recent meta-analysis of 95 randomized controlled trials comparing GDT versus standard hemodynamic care showed a reduction in mortality and complications, although a high risk of bias and poor methodological quality was again present in a number of included studies.
Studies specific to autologous breast flap surgery comparing standard care with GDT in combination with an Enhanced Recovery After Surgery (ERAS) protocol have shown a reduction in LOHS with no difference in complications. The average amount of intraoperative fluids used in the GDT group averaged 3.85 L versus 5.5 L in the preimplementation group.
Central line placement in free flap surgery is not indicated unless prolonged vasoactive infusions are anticipated. Central venous pressure monitoring does not improve hemodynamic optimization and has been associated with worse outcomes and complications from line placement. ,
Intraoperative oliguria defined as urine output of less than 0.5 mL/kg/h has not been correlated with acute kidney injury in noncardiac surgery. Oliguria should not be interpreted in isolation. Careful consideration of the patient’s comorbidities, the clinical context, and other hemodynamic parameters should be used as a guide for fluid resuscitation.
Choice of Intravenous Fluid Therapy
Consensus has been reached within the anesthesia community that perioperative IV fluid therapy to meet maintenance fluid requirements should consist of the infusion of balanced crystalloid solutions, with the avoidance of 0.9% saline. Administration of saline results in hyperchloremic metabolic acidosis and has been associated with renal dysfunction, increased LOHS, and increased mortality in patients undergoing noncardiac surgery. There is insufficient evidence to preferentially direct the choice of balanced crystalloid specifically for reconstructive surgery. Rate of infusion of maintenance crystalloid is pertinent in the perioperative management of these patients, primarily in the avoidance of iatrogenic fluid overload and the resultant effects on EG disruption previously discussed. A recent systematic review recommended intraoperative volume replacement during autologous tissue transfer surgery to be maintained between 3.5 and 6.0 mL/kg/h.
Ongoing debate continues regarding whether HES colloids are safe to administer in the perioperative period for volume therapy. Significant concerns regarding the use of HES and the risk of acute kidney injury in critically unwell patients have resulted in cautious perioperative use, although evidence from recent trials is challenging this mindset. A systematic review and meta-analysis of the impact of perioperative administration of HES reported no difference in risk of acute kidney injury in the elective surgical setting with colloid use, although the authors noted that trials were typically small and underpowered. Results from two larger randomized controlled trials recently published confirm these findings: GDT consisting of colloid versus crystalloid boluses revealed no increased risk of renal toxicity with colloid administration, with one study reporting an increase in disability-free survival in the treatment group. ,
A paucity of studies examining the effect of IV colloid infusion specifically during autologous reconstruction surgery exists. A single study compared the effects of HES and 5% albumin solution for volume replacement therapy during major reconstructive head and neck (HN) surgery, with both colloids effectively maintaining physiologic variables in the perioperative period. No difference in outcome was observed until an excess of 30 mL/kg HES occurred over a 24-h period, which was associated with coagulopathy and increased risk of allogenic blood transfusion. Allogenic blood transfusion has been associated with increased mortality and surgical site infection following free flap reconstructive surgery for oral cancer.
Historically, the rheological properties of dextran, a complex branched glucan polysaccharide, were thought to confer benefit in reconstructive flap surgery for prophylaxis of microvascular thrombosis. This ideology has since been disproved, with a significant increase in risk of flap failure with dextran use observed in high-risk oncologic patients, no observed benefit in flap survival, and an association with higher incidence of systemic complications, including unwanted bleeding, acute renal failure, allergic reactions, and cerebral edema.
Vasoactive and Inotropic Drugs
Utilization of vasopressor support in an attempt to improve end-organ perfusion and reduce perioperative complications requires consideration of not only the resultant mean arterial pressure achieved but also the context in which the vasopressor is used with regard to both circulating intravascular volume and adequacy of flow. Vasopressor use in the setting of hypovolemia may be detrimental to tissue and microcirculatory blood flow, and optimization of circulating volume prior to vasopressor use should be considered in the perioperative period.
It is known that sustained periods of intraoperative hypotension should be avoided due to their association with adverse outcomes: myocardial injury, acute kidney injury, and increased risk of mortality. A recent consensus statement from the perioperative quality initiative stated that even brief durations of systolic blood pressures <100 mmHg or mean arterial pressures <60–70 mmHg are harmful during noncardiac surgery. A novel trial reported that individualized targeting of systolic blood pressure within 10% of baseline value significantly reduced the risk of organ dysfunction compared with standard care.
The use of vasoactive and inotropic drugs during flap surgery remains contentious. Concerns exist that these drugs may cause anastomotic and flap microvascular vasoconstriction, limiting flap tissue perfusion. Multiple studies have demonstrated no link between perioperative vasoactive/inotropic agent use and flap complications, including flap failure. , The acute denervation of pedicle blood vessels changes their response upon exposure to vasoconstrictor agents. Specifically, they have an attenuated response; hence vasoconstriction may not occur at these sites despite the administration of a vasoconstrictor such as noradrenaline. This is in contrast to the vasoconstriction seen in innervated skin blood vessels. Another contributory explanation is the anticipated increase in the cardiac index with appropriate inotropic drug administration in normovolemic patients. This may result in increased flap perfusion.
With respect to choice of agent, noradrenaline increases free flap skin blood flow in hypotensive patients in a dose-dependent manner. Dobutamine increases free flap blood flow to a lesser extent without increasing mean arterial blood pressure. The use of dobutamine may be limited by tachycardia, especially in patients predisposed to ischemic heart disease. Adrenaline and dopexamine both decrease free flap skin blood flow and are not suitable agents for flap surgery. Milrinone, an inodilator, does not improve free flap outcomes and is associated with increased intraoperative use of vasopressor support.
Therapies Targeting the Endothelial Glycocalyx
Therapeutic approaches aimed to protect or restore the EG against injury represent a promising direction in clinical medicine. Strategies to reduce oxidative stress and inflammation may include the perioperative use of glucocorticoids, human plasma, plasma augmented with albumin, and IV lidocaine. There is currently insufficient evidence supporting the routine integration of these modalities into clinical practice.
Perioperative Considerations for Microvascular Free Flap Transfer Procedures
Patient outcomes are broadly determined by an interplay of three major variables: the extent of the surgical insult, the patient’s risk factors as determined by acute and chronic medical disease, and the quality of the perioperative care they receive.
The extent of tissue injury during flap reconstruction can be considerable. There may be numerous surgical sites, including the area of cancer ablation surgery, and one or more donor sites for flap harvesting. This may result in significant metabolic and physiologic derangements. Anticipating these disturbances is important for anesthetic planning and potential patient optimization.
Patient risk factors, as determined by their comorbidities and diseases of lifestyle, should be identified and modified where possible. There is emerging evidence that risk factors, such as smoking and hyperglycemia, affect the EG and predispose patients to inflammatory processes in the perioperative period. In addition, cancer burden and neoadjuvant therapies may further contribute to adverse outcomes. Adequate optimization might not be possible in the setting of time-pressured cancer surgery.
Perioperative care is ideally provided by a multidisciplinary team. The implementation of perioperative care bundles reduces variation in practice and aims to address modifiable factors leading to incremental and cumulative improvements in outcomes. , (See sections on Autologous Breast Reconstruction and Enhanced Recovery After Surgery for Autologous Breast Reconstruction .)
Perioperative Considerations
Identification and Optimization of Risk Factors Associated With Poor Flap Outcomes
Smoking and Nicotine Replacement Therapy
Smoking is an independent risk factor for complications in reconstructive procedures. It has been linked to deep surgical site infections, incisional dehiscence, and a higher return to theater rates. , Smoking causes harm via a number of pathways. Carbon monoxide alters the oxygen-carrying capacity of hemoglobin. Nicotine causes vasoconstriction and promotes the formation of microthrombi via catecholamine and thromboxane A2 release, respectively. Hydrogen cyanide impairs the function of enzymes implicated in cell metabolism. Combined, these factors contribute to impaired wound healing. Each week of abstinence allows reversal of some of these processes, with a significant benefit demonstrated at approximately 4 weeks. Preclinical animal studies link nicotine replacement therapy with wound healing complications; however, it is unclear if this translates into worse outcomes for reconstructive procedures. While nicotine replacement therapy is preferred to active smoking, complete cessation of both is preferable in the perioperative period.
Diabetes Mellitus and HbA1c
There is little research specifically assessing the impact of diabetes in patients undergoing reconstructive surgery. In the field of reconstructive breast surgery, studies have demonstrated a greater incidence of adverse outcomes in diabetic patients undergoing autologous breast reconstruction. This has not been demonstrated with implant-based breast reconstruction.
Current guidelines have been extrapolated from diabetic patients undergoing other major surgeries, cardiac and noncardiac, in which there is a demonstrable increase in both morbidity and mortality. Good preoperative glycemic control, as determined by HbA1c concentrations, is associated with a lower incidence of systemic and surgical complications, decreased mortality, and shorter LOHS.
Radiotherapy
Preoperative radiation to the recipient site causes fibrosis to the vasculature and surrounding tissue with an increased risk of flap-related complications. Complications include poor wound healing, fat necrosis, and flap loss. , Radiotherapy to the HN region is also a risk factor for a difficult airway.
Anemia
Anemia is defined as a hemoglobin level <13 g/dL for men and <12 g/dL for women. It is diagnosed in almost 50% of cancer patients during the course of their disease and is an independent risk factor for increased 30-day morbidity and mortality in patients undergoing major noncardiac surgery. In the setting of oncosurgery, the causes of anemia include impaired production of red blood cells (systemic inflammation, chemotherapy-related bone marrow suppression, and renal tubular toxicity with decreased erythropoietin production) and iron deficiency anemia (occult bleeding, decreased iron absorption).
Studies specifically assessing preoperative anemia in autologous reconstruction surgery did not show an association with surgical complications, including flap thrombosis or flap loss. Postoperative hemoglobin levels <10 g/dL were associated with increased LOHS and medical complications, but did not increase flap-related complications. , Intraoperative blood transfusion correlated with postoperative medical complications (mostly respiratory related), but again not with surgical complications.
Anterolateral thigh (ALT) free flaps were associated with more blood loss and have higher rates of intraoperative blood transfusion when compared with radial forearm free flaps (RFFF) and fibular free flaps.
Specific management of preoperative anemia involves a multidisciplinary approach targeting the likely causes of anemia. Proven therapeutic interventions include diet modification and IV iron therapy. Oral iron supplementation has reduced efficacy and does not meet the time constraints of planned surgery. Treatment of anemia with recombinant erythropoietin has been associated with symptomatic venous thrombosis in the setting of chronic inflammation in cancer patients. It is unclear if this translates into a risk for flap thrombosis. The modest benefit in treating anemia with erythropoietin in the short term may not justify this theoretical risk for flap thrombosis. Expert opinion should be sought.
In conclusion, preoperative anemia should be optimized to minimize the risk of transfusion-related medical complications. Anemia and perioperative blood transfusions are not independently associated with flap complications and therefore should not influence the consideration for blood transfusion.
Malnutrition
The prevalence of malnutrition in cancer surgery is reportedly as high as 47%. Causation can be multifactorial: secondary to the inflammatory or neoplastic disease, or due to altered metabolic state, poor access to nutrition, or gastrointestinal tract dysfunction. The Nutrition Risk Screening tool-2002 (NRS-2002) and the Subjective Global Assessment (SGA) tool are currently the most validated nutrition screening tools in the surgical population. The NRS-2002 is a good predictor of postoperative complications and can be used to predict mortality, morbidity, and LOHS.
Key elements of nutritional optimization involve provision of protein and micronutrient supplementation to increase muscle mass and support metabolic functions. There is currently no consensus on the duration of nutritional support. However, a 5- to 7-day duration of preoperative nutrition therapy is reported to reduce postoperative morbidity by 50%. The European Society for Clinical Nutrition and Metabolism guidelines advocate a 7- to 14-day supplementation period for severely malnourished patients.
Autologous Breast Reconstruction
General
Breast cancer is the most frequently diagnosed cancer worldwide, accounting for 23% of global cancer cases. Most will undergo lumpectomy or mastectomy as part of their treatment. Reconstruction timing and type (implant vs. autologous) varies geographically.
Commonly used free flaps for breast reconstruction include deep inferior epigastric perforator (DIEP) and transverse rectus abdominal musculocutaneous (TRAM) flaps. The donor sites for these methods are from the inferior abdominal area with vascular pedicles dissected from the deep inferior epigastric vessels. The internal mammary vessels form the recipient vascular pedicle.
Risk for developing complications after reconstruction depends broadly on patient comorbidities, type of reconstruction, and additional adjuvant therapies. Any combination(s) of risk factors seems to dramatically increase the risk of having poorer outcomes.
Comorbidities
Data extracted from the ACS-NSQIP database (United States) identified that the majority of patients having immediate reconstruction after mastectomy were American Society of Anesthesiologists (ASA) class II. Twenty-three percent of patients had hypertension and almost 5% were diabetic. Thirteen percent were active smokers. In this study factors linked with increased surgical complications were smoking, hypertension, diabetes, and obesity.
Obesity
Obese patients undergoing breast reconstructive procedures experience higher rates of wound-related complications and reconstructive failure. , , There is an appreciable increase in complication rates in patients with a body mass index (BMI) >30 kg/m 2 , with a significant increase beyond a BMI of 40 kg/m 2 . Notably, obese patients having implant-based reconstruction have a greater failure rate than autologous breast reconstruction, especially if the BMI is >35 kg/m 2 . Obese patients undergoing delayed breast reconstruction should be encouraged to lose weight until their BMI is within an acceptable range.
Type of Reconstruction
Compared with implant-based reconstruction, autologous reconstruction involves a more substantial operation with a longer recovery time. It is associated with an increase in surgical complications in the short term, but compared with implant-based reconstruction, this risk diminishes over time.
Adjuvant Therapies
Radiotherapy
Postmastectomy radiotherapy (PMRT) for node-positive breast cancer reduces the risk of local recurrence and improves overall survival. However, it is unfortunately associated with increased reconstruction failure and complications, regardless of the reconstructive method. Compared with implant-based reconstruction, autologous reconstruction is associated with significantly fewer postoperative wound complications. In a study of bilateral autologous reconstruction, there were an increase in complications on the irradiated side. Common complications associated with recipient site radiotherapy include flap fibrosis, fat necrosis, and wound dehiscence.
Radiation-Induced Heart Injury
Radiotherapy to the thorax can cause pathologic changes to the heart, blood vessels, and lung tissue. It causes an acute increase in reactive oxygen and nitrogen species and can lead to acute endothelial dysfunction and long-term tissue fibrosis. Patients who received postoperative radiotherapy for breast cancer have higher rates of mortality associated with ischemic heart disease, and may have signs and symptoms of congestive cardiac failure. Further investigation and referral may be needed.
Hormone Inhibitors
Adjuvant therapy for estrogen receptor-positive breast cancers includes hormone inhibitor (HI) agents such as tamoxifen (selective estrogen receptor modulator) and letrozole (aromatase inhibitor). These drugs decrease the constitutive effects of estrogen in the skin, impacting wound healing and increasing rates of high-grade prosthetic capsular contractures. HI agents have been implicated in microvascular thrombotic events resulting in thrombotic flap complications and total flap loss. There is conflicting evidence regarding the systemic thromboembolic phenomenon; however, there is likely to be a contributory role. Temporary cessation of these agents is recommended, although there is currently no consensus regarding the timing of this. Considering the pharmacodynamic properties of these drugs and timing of postoperative complications, cessation 2–4 weeks prior to surgery and recommencement 2 weeks postoperatively has been suggested. No studies have demonstrated a decrease in cancer survival rate with temporary discontinuation of HIs.
Chemotherapy-Induced Cardiac Toxicity
Systolic dysfunction may develop in breast cancer patients treated with anthracyclines (doxorubicin) and trastuzumab (targets human epidermal growth factor receptor 2 [HER2]). Further investigation and referral may be needed.
Enhanced Recovery After Surgery for Autologous Breast Reconstruction
There is mounting evidence demonstrating the benefits of ERAS implementation within several surgical fields. Currently there are only a few quality studies , , evaluating the outcomes after ERAS implementation in autologous breast reconstruction. These studies had several common findings and are summarized below:
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Fasting periods were limited to 2 h preoperatively with early resumption of eating and drinking in the postoperative period. There were no incidences of aspiration reported.
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Multimodal analgesia included regular paracetamol and a nonsteroidal antiinflammatory agent. Regional techniques such as transverse abdominis plane (TAP) blocks were used. The decreased reliance on parenteral opioids and earlier transition to oral analgesia resulted in a reduction in total opioid and antiemetic use. A common finding in these studies was a positive correlation between the total amount of opioids used and LOHS.
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GDT resulted in a reduction of the amount of intraoperative fluid volumes administered. The average amount of intraoperative fluids used in the GDT group was 3.85 L versus 5.5 L in the non-GDT group.
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Thromboprophylaxis was started in the early postoperative period with no significant difference in hematoma formation.
There was no difference in major complications between groups, implying that the above measures are safe and effective. LOHS was decreased by an average of 1 day.
The ERAS Society has published consensus recommendations pertaining to reconstructive procedures. This includes Head and Neck and Breast surgery, respectively.
Head and Neck Cancer Resection With Immediate Flap Reconstruction
General
HN neoplasms form the fifth most common cancer worldwide and originate most frequently from the mucosa of the upper oral cavity, pharynx, larynx, nasal cavity, and sinuses. Less frequently, neoplasms originate from the salivary glands, thyroid, soft tissue, bone, and skin. Squamous cell carcinoma and papillary thyroid cancer are commonly seen.
Etiology
The etiologies of HN cancers are an interplay between host and environmental factors. Many of these factors are dose-dependent and synergistic (e.g., alcohol and tobacco).
Host factors
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Immunosuppression (human immunodeficiency virus infection, chronic immunosuppression after organ transplantation)
Environmental exposure
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Alcohol abuse
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Tobacco
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Infection with human papilloma virus and Epstein-Barr virus
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Ionizing radiation
Demographic
Patients with HN malignancies are most commonly male and elderly. There are, however, an increasing number of younger patients due to exposure to human papilloma virus. A recent review found that the average overall complication rate was 48% with flap success rates nearing 95%. The mortality rate was between 1% and 2%. The incidence of complications was found to be directly related to the comorbid state of the patient, rather than the age. There are several comorbidity scores that can help predict flap survival rates and complications. The Kaplan-Feinstein index (KFI), Adult Comorbidity Evaluation-27 (ACE-27), ASA score, and the Index of Coexistent Diseases (ICED) score correlated well with flap survival and complication rates. Pertinent comorbidities that are strongly associated with flap failure rates include diabetes and chronic obstructive pulmonary disease. Hypertension was present in 64% of patients but was not associated with worse outcomes. Pulmonary and cardiac complications were frequently seen in the postoperative period. , ,
Commonly Used Free Flaps in HN Reconstruction
Resection of complex tumors in the HN area can have major functional and aesthetic consequences. Flap reconstruction plays a major role in the restoration of form and physiologic function. The most common musculocutaneous free flaps are RFFF and ALT flaps, whereas fibula free flaps are the most common osteocutaneous flaps.
Airway Planning and Postoperative Destination
Patients undergoing surgery for HN tumors should undergo a thorough airway assessment. HN cancer patients have a high rate of difficult intubation compared to other patient groups. , Distortion of the upper airway by prior surgery, irradiation, or bulky and friable tumors may make oxygenation difficult after induction of anesthesia. Thirty-nine percent of airway cases reported in National Audits Project 4 (NAP4) had HN pathology.
Airway choice and location should be discussed with the surgeon, as this will vary depending on the location and extent of surgery. A tracheostomy may be inserted prior to commencement of resection, or a nasal tube may be required.
HN patients may also be at risk of postoperative airway obstruction. A discussion between surgeon and anesthetist at the end of the case is essential to forming a clear airway plan. Documentation should include the ease of airway management at the start of the case, likely changes after reconstruction, and any airway examination performed at the end of the case. Flap position and potential flap damage from airway maneuvers should also be considered. Surgical procedures that carry greatest risk of postoperative airway occlusion include bilateral neck dissection and resection of the mandible, tongue, and floor of mouth. Free flap edema may cause additional narrowing of the aerodigestive tract. The RFFF is smaller and more pliable than other commonly used flaps and poses less risk. The Cameron tracheostomy scoring system takes surgical risk factors into consideration with a threshold score of more than five points prompting consideration for elective tracheostomy placement. It does not take into consideration the cardiopulmonary reserve of the patient, and this should be evaluated in conjunction with surgical risk factors for the planning of appropriate postoperative destination and ventilation. Patients with adequate cardiopulmonary reserve undergoing free flap reconstruction for unilateral neck dissection may be considered for overnight sedation and delayed extubation, instead of elective tracheostomy placement.
It should be noted that not all HN reconstruction patients will require postoperative ventilation in an intensive care unit. Indeed, the hemodynamic side effects of sedation can have a negative effect on flap perfusion. Carefully selected patients may recover in wards with specialized nursing staff trained to identify flap and airway compromise and escalate management where appropriate.
The Cook Staged Extubation Set includes an airway wire that can be left in the trachea after extubation. This allows insertion of the included reintubation catheter over the wire enabling oxygenation and reinsertion of an endotracheal tube if required. It does, however, require appropriate training of staff and has some limitations.
Analgesia
HN patients have high rates of neuropathic pain due to either direct tumor effect or secondary to cancer treatment. Specialist pain input may be needed. Patients who have had bone harvested generally require a plaster cast and the donor site may be more painful than the reconstruction. Due to limited oral intake, IV analgesia is often required.
Feeding
Oral intake may be limited after a major reconstruction. Some patients will require nasogastric feeding, and if this is the case, a nasogastric tube can be inserted under direct vision at the end of surgery.
Postoperative Delirium
Postoperative delirium is commonly seen after HN reconstruction. It is defined as a reversible neurologic deficit and is characterized by fluctuations in conscious level and a change in cognition. Several risk factors have been identified and include age above 70 years, male sex, prolonged surgery, intraoperative blood transfusions, tracheostomy placement, and ASA physical status above III. It is commonly seen within the first 3 days of surgery. Postoperative agitation and disorientation seen with postoperative delirium may lead to surgical anastomotic disruption and flap compromise. Early identification and specialized intervention are imperative and may include a short period of intubation and ventilation in an intensive care unit.
Patients presenting with HN tumors may have a history of alcohol abuse. Acute alcohol withdrawal may present in the postoperative period as confusion, agitation, and generalized seizures, putting the patient at risk for surgical anastomotic disruption. Patients should be screened and managed appropriately.
Patient Positioning and Pressure Care
The duration of free flap surgery can be long and may exceed 8 h. This brings unique challenges with regards to positioning, access to the patient, and pressure care. To avoid injury of the brachial plexus and ulnar nerve, shoulder abduction should be less than 90 degrees and arms in the neutral position, respectively. The patient needs to be adequately positioned and secured to allow for intraoperative assessment of symmetry. Attention should be paid to avoid focal areas of pressure caused by cables, gown knots, or inadequate cushioning. Vulnerable areas include the heels, sacrum, and occiput. Consider passively moving joints for extended procedures to avoid joint stiffness and pressure areas.
Free Flap Breast Reconstruction
For delayed reconstruction, the patient will be supine with the arms adducted for the duration of the surgery. For patients undergoing simultaneous mastectomy and immediate reconstruction, the arm position may start in the abducted position to allow access to the axilla. The arms are then adducted for the reconstruction part of the procedure.
Distal venous and arterial line access points will not be readily accessible during surgery; therefore extension lines and/proximal access points will be needed. For the same reason, two peripheral venous access sites are advised. Care should be taken to avoid pressure injuries secondary to lines and access points. Central venous access is not routinely used, unless the prolonged use of inotropes or vasoactive drugs is anticipated. It should be noted that peripheral venous access points will not be visible or readily accessible should a total intravenous anesthetic (TIVA) technique be employed. There is ongoing debate on the acceptability of the approach and whether a central venous line with its potential placement complications is justified.
The anterior superior iliac spine should be in line with the break of the table to allow table flexion to assist donor site closure. To minimize tension on the donor site wound, the patient will remain with their hips in flexion for 24–48 h postoperatively. For this reason, the ward bed should be appropriately positioned prior to transfer from the operating table.
HN Reconstruction
Theatre layout will depend on the location of the flap donor site, the backup donor site, and the area of tumor excision. Generally, the head of the patient will be distant to the anesthetic machine with the flap donor site exposed and accessible to the surgical team(s). The eyes should be occluded with a watertight dressing and appropriately shielded if surgery does not include the ocular area. A head ring and shoulder roll are frequently needed to gain adequate access to the HN area. The endotracheal tube and airway connectors will not be readily accessible during the case and should be adequately secured. Long airway circuits are frequently used and arranged either cephalad or caudally depending on the surgery location. Pressure areas caused by circuit, connectors, and heat and moisture filter should be avoided. Particular care should be taken to avoid pressure injuries caused by nasally placed endotracheal tubes. The head may be slightly elevated to avoid venous congestion and venous bleeding from surgical sites.
Central venous access is not routinely placed for HN surgery. If prolonged use of vasoactive agents is anticipated, femoral central lines on the contralateral side to the surgical site are advised. If a radial forearm free flap is considered, vascular access and invasive monitoring should be placed on the contralateral arm.
Monitoring
Routine intraoperative monitoring should be used during free flap reconstruction procedures. In addition, invasive arterial blood pressure monitoring allows for arterial blood gas analysis. The arterial partial pressure of oxygen and carbon dioxide should be kept within physiologic limits. Urine output should be measured via an indwelling catheter. Core temperature may be measured via an indwelling catheter or via a temperature probe placed in the esophagus. Nerve monitoring may be required if resection close to the recurrent laryngeal nerve is undertaken. Optional equipment includes depth of anesthesia monitoring, peripheral nerve stimulation, pulse contour analysis systems, or esophageal Doppler monitoring.
Anesthetic Maintenance
With respect to free flap outcomes, maintenance of anesthesia using propofol as a TIVA agent has not been proven to be superior over inhalational anesthesia. However, anesthetic maintenance with propofol reduces the incidence of PONV, , possibly reducing the risk of anastomosis disruption due to retching and vomiting. In the setting of oncosurgery, propofol may have a cancer survival benefit by inhibiting cancer cell migration and preserving the function of natural killer and T cells. In a single-center retrospective study of more than 7000 cancer surgery patients there was an increased risk of death in patients receiving an inhalational compared with propofol-based anesthetic.
Multimodal Analgesia
Good analgesia mitigates the surge of stress hormones as well as the vasoconstrictive response to pain. The paradigm of multimodal analgesia is advocated and widely practiced for postsurgical pain. The concept involves the use of combinations of analgesic agents with different modes of action to achieve improved analgesia and reduced opioid requirements. This includes the use of antiinflammatory agents, regional techniques, and other adjuvants in addition to opioids. The concept of preemptive analgesia describes the reduction in magnitude and duration of postoperative pain by applying antinociceptive techniques prior to tissue injury. While there is no definite evidence to show improvement in postsurgical pain control, there may be a role in reducing the development of chronic postsurgical pain.
Lignocaine Infusions
The incidence of chronic postsurgical pain is high in breast surgery, with an incidence up to 65%. , Even minor procedures such as lumpectomy and sentinel lymph node dissection have a 40% incidence, with mostly a neuropathic component. Perioperative lignocaine infusion is associated with a modestly decreased incidence of chronic postsurgical pain in the setting of mastectomies. Postulated mechanisms include its sodium channel blocking mechanism of action, as well as antiinflammatory and antihyperalgesic properties. Intraoperative IV lignocaine infusion combined with postoperative subcutaneous lignocaine infusion reduces pain at rest, cumulative morphine consumption, and LOHS in the setting of major colorectal, urologic, and neuropathic cancer pain settings.
Nonsteroidal Antiinflammatory Drugs and Cyclooxygenase-2 Inhibitors
In a retrospective cohort study of autologous breast reconstruction comparing perioperative ibuprofen versus celecoxib, celecoxib was not associated with an increase in flap failure rates. There was a threefold increase in postoperative hematoma formation in the ibuprofen group. It should be noted that patients in both groups received additional aspirin as an antiplatelet agent. Another autologous breast reconstruction study did not show a correlation between perioperative ketorolac administration and postoperative hematoma formation.
Gabapentinoids
The administration of gabapentinoids such as gabapentin and pregabalin preoperatively improves postoperative acute pain with an opioid-sparing effect, although there is no evidence for prevention of chronic postsurgical pain.
Regional Anesthetic Techniques for Autologous Breast Reconstruction
The abdominal donor site is the major contributor to pain in autologous breast reconstructions.
Epidural
Intraoperative epidural use has been described in a small study of 99 patients. In this study, the group receiving general anesthetic with intraoperative epidural had improved pain scores, a decrease in opioid consumption, and lower PONV scores, compared with the general anesthetic alone. The need for vasopressor support was marginally higher in the epidural group, presumably to correct epidural-associated vasodilatation and hypotension. This study did not compare the total volume of perioperative IV fluid used. There was no significant difference in postoperative complications. Postoperative hypotension and delay in mobilization associated with epidural use may make this technique less favorable.
Transverse Abdominis Plane Blocks and Rectus Sheath Block
TAP and rectus sheath blocks, with or without catheter placement, resulted in reductions in postoperative opioid consumption, better PONV scores, and a reduction in LOHS. , , ,
Postoperative Nausea and Vomiting
PONV remain common with an incidence ranging from 25% to 60%. Vomiting can have several detrimental effects on flap outcomes. Complications include wound dehiscence, hematoma formation, and reduced patient satisfaction. The Apfel score is a useful tool that predicts risk of PONV based on the number of patient factors. These factors include the use of postoperative opioids, nonsmoking status, female sex, and history of PONV or motion sickness. Based on the score, the patient would be categorized as low (0–1 risk factor), medium (2 risk factors), or high risk (3 risk factors). The recommendation from the Australian and New Zealand College of Anaesthetists is to monitor for low risk, one to two interventions for medium risk, and more than two interventions for high risk.
Temperature Management
While there is theoretical evidence to suggest hypothermia reduces pedicle thrombosis, , this has not been proven in the clinical setting. Instead, intraoperative hypothermia may pose a risk for the development of flap infection with no benefit to anastomotic patency in free tissue transfer. Preoperatively, patients should be actively warmed. Exposure for surgical site marking by the surgical teams should be kept to a minimum, or should be completed the day prior to surgery. Intraoperatively, the patient should be actively warmed, and IV fluid warmers should be utilized. As HN patients often only have a small surface area exposed, these patients have a tendency to develop hyperthermia; thus vigilance with active warming is required.
Venous Thromboembolism Prevention
The 2005 Caprini Risk assessment model is a risk stratification tool that has been validated in reconstructive patients to calculate the 6-day VTE risk. Individualized measures to prevent VTE are recommended according to the risk category and include mechanical (compression stockings) and chemical (enoxaparin/heparin) prophylaxis. Contraindications and potential risk of bleeding should be assessed prior to determining the appropriate method of prophylaxis. Postoperative bleeding into HN surgical sites can have catastrophic consequences and this must be considered when weighing up the risks and benefits of chemical prophylaxis. Most patients undergoing free flap reconstructive procedures in the setting of malignancy will fall into the high-risk category of developing VTE.
On review of the literature, it was noted that there was variation in practice in terms of dosing, duration, and timing of administration of VTE prophylaxis. Doses ranged from 30 to 60 mg enoxaparin daily, adjusted for weight and renal function. Timing of drug administration ranged from 1 h preoperatively to 12 h postoperatively. Duration of drug administration varied according to the risk stratification score. Review of these protocols did not provide sufficient evidence to dictate administration protocols.
In the setting of flap reconstruction, the observed rates of clinically significant reoperative hematoma are not increased with the use of perioperative enoxaparin or unfractionated heparin. Dextran is associated with an increase in hematoma formation, cardiac and respiratory complications, anaphylaxis, and flap loss. Aspirin is associated with increased hematoma formation. Of note, postoperative administration of aspirin, dextran, heparin, and low-molecular-weight heparin have no protective effect against the development of pedicel thrombosis and no significant effect on flap survival overall.
Antibiotic Regimen
Systemic antibiotic prophylaxis given preincision and continued for 24 h postoperatively is recommended for breast surgery, and clean-contaminated surgery of the HN. The most commonly isolated organisms in plastic surgery are Staphylococcus aureus and streptococci. In clean-contaminated HN surgery, organisms include anaerobic and gram-positive aerobic organisms. Patients with wound infections may have polymicrobial colonization with gram-negative aerobic and anaerobic organisms. Local guidelines should guide antibiotic use due to regional variations in organism sensitivity. Administration of repeat doses of IV antibiotic should be given in prolonged procedures. The overall duration of antibiotic therapy should be limited to less than 24 h as the benefit beyond this has not been demonstrated. ,
Postoperative Considerations
Key aspects for optimal postoperative flap care include:
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Gentle anesthetic emergence
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Optimization of flap perfusion
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Postoperative flap monitoring
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Safe and comfortable recovery
Anesthetic Emergence
Any sudden increases in intrathoracic pressure may disrupt the surgical anastomosis with potential hematoma formation. Measures to minimize coughing, vomiting, shivering, and excessive movement should be employed. Any blood or secretions should be cleared from the airway while the patient is still anesthetized. It may be useful to reexamine the airway at completion of HN surgery. A slow emergence with the patient already transferred onto a ward bed is advised. Humidified air and oxygen might reduce airway irritation and coughing postextubation.
Optimization of Flap Perfusion
Careless postoperative IV fluid administration can negate the meticulous steps taken intraoperatively to optimize the hemodynamic status of the patient. IV fluids can be discontinued once a patient is stable and tolerating oral fluids. A degree of postoperative oliguria can be expected in the early postoperative period. It is a normal neurohormonal response to surgical stress and is a poor indicator of overall fluid status. A low urine output interpreted in isolation should not trigger unnecessary IV fluid administration.
Cardiovascular complications are common in postoperative HN reconstruction patients and should be excluded in hemodynamically unstable patients. Clinical assessment includes urgent review of vital sign trends, wound sites, drain output, and fluid balance charts. The passive leg raise test is a useful bedside maneuver to assess fluid responsiveness. It has been validated in nonventilated patients with or without arrhythmias. Fluid responsiveness is defined as an increase in cardiac output (or its surrogate) of more than 15% following passive leg raise. These patients may benefit from fluid resuscitation to improve hemodynamic status. Ongoing hypotension or low cardiac output despite fluid resuscitation warrants specialist review and treatment.
Specific attention is required to ensure that the flap pedicle is not compressed by equipment or dressings. HN reconstructions may be compromised if neck vessels are kinked, stretched, or compressed by adjacent structures or drains. The head should therefore be maintained in a neutral position postoperatively.
Postoperative Flap Monitoring
Postoperatively, patients require dedicated nursing staff with experience and expertise to diagnose early flap compromise. Microvascular thrombosis occurs most frequently within the first 72 h, reflecting the need for more frequent and intensive flap observations during this time. Subjective assessment of flap health includes observation of color, temperature, turgor, and changes in appearance. More objective monitoring methods include the use of Doppler devices, near infrared spectroscopy, and indocyanine green fluorescent videoangiography. , Insufficiencies of arterial inflow and venous congestion should be diagnosed promptly and may warrant urgent surgical exploration.
Pulmonary Function and Early Mobilization
Postoperative pulmonary complications can be reduced by implementing a multidisciplinary perioperative respiratory care bundle. Components of this bundle include perioperative incentive spirometry; cough and deep breathing exercises; oral care, including perioperative chlorhexidine mouthwashes, patient education, early mobilization, and head of bed elevation. Adequate pain management, prevention of PONV, and timely removal of catheters and drains may promote early mobilization.
Conclusion
Outcomes after autologous free flap reconstruction depend on the interplay between multiple factors. The implementation of perioperative care bundles reduces variation in practice by addressing modifiable factors known to alter outcomes. This may lead to incremental and cumulative improvements in care. Appreciation of the pathophysiologic determinants of flap perfusion and the consequence of therapeutic interventions will permit a more considered approach.
References
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