Anaesthetic Challenging in Microsurgical Flap Reconstruction: A Systematic Review

Background: Anaesthetic management for microvascular reconstructive surgery is challenging and clearly affects the risk of major complications such as flap hypo-perfusion. In this systematic review we explore recent (last 7 years) clinical evidences related to perioperative management and anaesthetic controversy of patients undergoing microvascular reconstructive surgery, especially focused on head and neck surgery with free flaps (FF) and breast reconstructive surgery with deep inferior epigastric perforator flap (DIEP-flap). Methods: A literature search of published clinical studies between 2011 and 2018 was conducted, yielding a total of 4307 papers. Only 150 were eligible, according inclusion and exclusion criteria. Results: 62 studies were selected for this review and categorized in 3 groups: preoperative-intraoperativepostoperative anaesthetic management and areas of controversy for patients undergoing head and neck surgery with FF and breast reconstructive surgery with DIEP-flap. Discussion: Anaesthetic management for flap reconstructive surgery remains an open field of interest with limited evidences regarding a standard care. Main components of research currently are: the need to join standard multidisciplinary enhanced recovery pathways, as well as the necessity to develop a standard intraoperative management. In theatre, the recent hemodynamic parameter “Hypotension Probability Indicator” (HPI) is promising: the advantage to predict a drop in the mean arterial pressure can be more effective than a fluid therapy titrated to maintain SVV less than 13%. Prospective studies are necessary to clarify.


Introduction
Microvascular flap surgery is one of the best and fine options for reconstruction in head and neck cancer patients, plastic, trauma and burns [1].
Anaesthetic management in these settings has limited evidences of standard care and clearly affects the outcome, with high impact on flap survival. Main areas of controversy for anaesthesiologist involve the need to take part into standard multidisciplinary enhanced recovery after surgery protocols (ERAS protocols), as well as a standard perioperative management, especially in terms of pre-operative assessment, hemodynamic monitoring, goal-directed fluid therapy, thermoregulation, flap monitoring, deep vein thrombosis (DVT) prophylaxis, intensive therapy unit admission (ITU), early mobilization, antibiotics guidelines, analgesia [2].

Results
A total of 4307 papers were retrieved using the keywords, only 1070 were assesses for eligibility. According the inclusion criteria, 62 were selected and categorized in 3 groups ( Figure 1): • Preoperative anaesthetic management and areas of controversy for patients undergoing microvascular reconstructive surgery. • Intraoperative anaesthetic management and areas of controversy for patients undergoing microvascular reconstructive surgery. • Postoperative anaesthetic management and areas of controversy for patients undergoing microvascular reconstructive surgery. For more information, visit www.prisma-statement.org.

Risk stratification
Patients presenting for head and neck FFs surgery and breast reconstructive surgery are fragile cancer patients with a number of dangerous co-morbidities [5]. Hence, pre-operative assessment and investigations play a role for the risk stratification [6]. Although technical issues are prevailing factors, clinical characteristics also contribute to flap failure [7]. The Division of Plastic and Reconstructive Surgery, University of Southern California, investigated a number of non-technical variables in 2015, using the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database. Univariate analysis was conducted to determine the association of FF failure with the individual factors: age, gender, ethnicity, body mass index, intraoperative transfusion, diabetes, smoking, alcohol, American Society of Anaesthesiologists classification, year of operation, operative time, number of flaps, and type of reconstruction. Flap loss rate was 4.4%. Operative time was the only significant independent risk factor, as resulted from the multivariate logistic regression [8]. According the analysis conducted by another plastic unit in Istanbul, patient's age was not an independent variable for increased risk in microvascular reconstruction. However, operative time and reconstruction sites were associated with higher incidence of complications and ITU admissions [9]. Another important study, held in Toronto in 2016, recognized operative time and smoking as the independent risk factors for intraoperative complications in reconstructive breast flap surgery [10]. Several preoperative investigations play a role in the risk stratification of these patients. Studies revealed how cardiopulmonary exercise testing (CPET) in complex patients is pivotal to assess the functional capacity. Many institutions routinely use CPET to design the operation and to inform patients about risks and benefits of surgery [11]. In conclusion, flap ischemia is a multifactorial event and, according recent literature, demographics and medical patient's characteristics such as: age, ethnicity, radiation, and chemotherapy, medical comorbidities, smoking, are not independent risk factors. Preoperatively, patients need to be assessed to ensure the best perioperative management but intraoperative management and technical variables may have higher importance for the outcome [12].

Nutrition, preoperative fasting and preoperative education
According recent evidences, the basic nutritional state should be estimated and optimised: preoperative quantity of albumin has inverse correlation with wound dehiscence, fistula, salivary leak, pleural effusion, renal function [13]. Preoperative fasting should be minimal. In patients eligible for oral intake, clear solids should be allowed up to 2 h and clear fluids up to 6 h before anaesthesia [14,15]. All patients undergoing major head and neck cancer surgery with FFs and breast reconstructive surgery should be adequately prepared regarding the surgical journey and evidences suggest they should receive a systematic teaching. If anaesthetists and qualified health professionals should share this discussion, is still not clarified, due to shortage of specifically focused trials [16]. In conclusion, the implementation of a multidisciplinary pre-operative evaluation driven by anaesthetists, nutritionists, other medical specialists and health practitioners may reduce post-operative complications derived from pre-existing conditions [17].

Intraoperative Anaesthetic Management and Areas of Controversy for Patients Undergoing Microvascular Reconstructive Surgery
As we highlighted in the previous chapter, intraoperative management has great influence for the surgical outcome and the anaesthetist plays a pivotal role [12].

Fluid management
Different studies, demonstrated the predictive relationship between the quantity of intraoperative fluid administrated and the rate of postoperative complications in FF surgery [18,19]. From the analysis on 154 patients with head and neck reconstructions with fibular FFs, fluid volume higher than 5500 ml was associated with an increase in medical and surgical complications, and a cut-off value of 7000 ml was identified as the only significant risk factor for major complications [19]. FFs don't present lymphatic drainage, therefore, every anaesthesiologist needs to consider these characteristics in order to maintain intravascular blood volume, prevent flap oedema and the pro-coagulant state due to rapid administration of crystalloids [20]. Regarding the use of colloids, data have shown that volume higher than 20-30 ml/kg/24 h can increase perioperative morbidity, and Hydroxyethyl starch seems more promising to expand plasma volume and reduce blood viscosity if compared to gelatine-based colloids [21]. Every patient can be identified as fluid responsive by measuring cardiac output (CO), cardiac index (CI), stroke volume or pulse pressure variation (SVV, PPV). According recent literature, a goaldirected fluid therapy, titrated to keep SVV ≤ 13%, with the use of mini invasive arterial pulse contour device, results in improved oxygen delivery and reduces the intravenous fluid administration, with better outcomes [22]. We will discuss later on in this paper, other details regarding hemodynamic monitoring.

Haemoglobin
Haemoglobin target is a sliding value in head and neck and plastic microvascular surgery. In UK, as a resulted from a national survey, practice for blood loss in theatre is varied, with a mean trigger for blood transfusion of Haemoglobin 7.8 g/dl [21]. Even if flap perfusion and peripheral oxygen delivery is a priority, several observational studies in head and neck cancer have highlighted how allogenic blood transfusion is associated with higher rate of postoperative complications and worse prognosis, and anaesthesiologist usually follow blood conservation strategies in high-risk patients [23].

Blood Pressure (BP) management
BP management, again, is not well standardised in this type of surgery, and enhancement of flap perfusion in theatre is always a priority. The use of vasopressors in FFs surgery is a matter of controversy. Evidence from animal models has revealed that the use of vasopressors leads to vasoconstriction in the microcirculation of the flap; however, this has not been shown in the clinical settings [24]. According different clinical studies, a general intraoperative well recognized target for mean arterial blood pressure (MAP) during anastomosis is a value equal or major than 70 mmHg, while a MAP lower than 60 mmHg is considered "hypotension" [25]. Dobutamine and vasoconstrictors can be safely used if the goals for BP and CI are not achieved with SVV<10-13% [25][26][27].

Glycaemic control
Stress hyperglycaemia is a very common feature of complex patients: targets and relationships with outcome are not clear, with contrasting results from literature [28]. Authors from the national survey in UK evidenced how the majority of anaesthesiologist, involved in head and neck FFs reconstructions, would intraoperatively commence an insulin infusion at a blood sugar level of 10-12 mmol/l, a minority of them would use a slightly higher trigger of 12-14 mmol/l [21]. The tightlinkbetweeninsulinand thebrain, with discernible effects on memory, learning abilities, and motor functions in fragile patients has been widely explored in literature by a number of authors [29].

Type of anaesthesia
Only few studies, evaluate the impact of anaesthesia management in microvascular reconstructive surgery. One of these recently recorded the differences between patients who received inhalation and total intravenous anaesthesia (TIVA) in FF surgery [30]. Patients in the TIVA group required less perioperative fluids (both crystalloid and colloid) to maintain hemodynamic stability, furthermore, after multivariate regression, patients in the TIVA group had a significantly reduced risk of pulmonary complication compared with the inhalation group. Some anaesthetist may be concerned about the possibility of metabolic acidosis-propofol infusion syndrome (PRIS)-which would cause damage to a fresh anastomosis in flaps. The association between PRIS and propofol infusion is demonstrated only for doses higher than 4 mg/kg/h when the duration lasts longer than 48 h [31]. Moreover, as part of a good anaesthetic strategy, patients undergoing head and neck or plastic cancer surgery should always receive intraoperative medications to mitigate postoperative nausea and/or vomiting (PONV) and a combination of corticosteroid and antiemetic is always indicated [32].

Antibiotics
Many patients undergoing FFs surgery have a number of risk factors potentially able to trigger postoperative infections (alcohol, smoking abuse, radiation, chemotherapy, poor nutritional status, long operation time). In this setting, antibiotic prophylaxis is still under debate and every centre has specific protocols. From a number of international studies, the choice of antibiotic appears to affect the incidence of postoperative infections and flap site infections more than the duration [33,34]. From a number of evidence ampicillin-sulbactam or cefuroxime are the preferred prophylactic antibiotic for major cleancontaminated head and neck procedures, less than or equal to 24 h ofantibiotic prophylaxis is likely sufficient. Clindamycin prophylaxis increases the risk of recipient surgical site infection, moreover, for patients with penicillin allergy, broader gram-negative coverage is recommended [33,35,36].

Intraoperative monitoring
Again as a result forms the UK national survey, in theatre, a number of anaesthesiologists use additional monitoring including: core temperature, central venous pressure, bispectral index (BIS), cardiac output monitoring (CO monitoring). Temperature monitoring is pivotal to ensure normothermia and the urinary bladder thermistor catheter correlates well with pulmonary artery thermistors [21,37]. Recent guidelines suggest that hemodynamic monitoring should be used in high risk patients undergoing major surgery to enhance fluid optimisation, reduce mortality, morbidity and reduce costs. Flo/Trac Vigileo system, based on arterial waveform analysis, and patient's age, sex, height, weight is often used in FF reconstructive surgery as mini invasive and reliable [38]. As additional parameter, the recent "Hypotension Probability Indicator" (HPI) could be promising: the advantage to predict a drop in the mean arterial pressure, before hypotension occurs, can be more effective than a fluid therapy titrated to maintain SVV less than 13% [39]. Prospective studies are required to investigate the relationship between HPI and flap perfusion in theatre ( Figure 2) [40].

ITU admission
A number of recent studies support that uncomplicated FFs patients may be safely assisted outside ITU [41,42]. Panwar et al. recently, with an interesting cohort study, tried to understand if postoperative management in ITU is necessary. Ninety-nine patients were included in the historical cohort of ITU patients, and 157 patients were enrolled in the prospective arm after creation of a head and neck surgical unit. They noted no significant changes in flap survival, inpatient morbidity, or mortality. They did, however, note a significant 1-day reduction of hospitalization and a reduction in total costs [41,42]. From an interesting survey held in USA, nurses employed in an academic medical center and nurses with more than 5 years of experience were significantly more comfortable with their ability to care for microsurgical patients [43]. Ideally, uncomplicated patients receiving microvascular surgery should be step down in high-dependency units or equipped specialized surgical units, however, the pivotal role of nursing and health practitioner staff cannot be underestimated, such as their workload.

Early postoperative extubation and tracheostomy
Airway management in patients undergoing major head and neck procedures with FFs reconstruction includes the protection of the airway if bleeding, swelling and oedema occur. Surgical tracheotomy has rare severe complications but presents the danger to prolong the hospital stay. According the last indications of ERAS protocols, the decision to perform a tracheotomy is now linked to the presence of specific conditions such as advanced cancer stage and location, otherwise, early extubation is always preferred [15].

Early feeding
Recent recommendations support early re-entrance of enteral nutrition in head and neck FFs and DIEP-flap reconstructive surgery [44,45]. However, for head and neck patients, considerations as risk of wound dehiscence, fistula, and aspiration must be done. Recent studies compared early (prior to postoperative day 6) and late oral intake groups (postoperative day 6 or late) and the "early" group was not linked to any increased morbidity or adverse outcome, at the same time, duration of hospital stay was lower [46,47]. Enteral feeding via either nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tube is now recommended up to 12 h after surgery.

Pain management
Opioid-sparing and multimodal analgesia, prescribing nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors (COX inhibitors), and paracetamol, is safe, effective, able to reduce narcotic side effects and to facilitate rapid recovery after surgery: when this approach is not sufficient, patient controlled analgesia (PCA) can be eligible [48]. For plastic reconstructive surgery with DIEP-flaps, additional nerve blocks can be considered, such as the transversus abdominal plane block (TAP block), while small catheter injecting local anaesthetics can be promising in a number of head and neck reconstruction such as FFs with fibular harvest [49,50].

Flap perfusion monitoring
Postoperatively, a number of different instruments are accountable to assess flap perfusion and viability including: Doppler, implantable Doppler, micro-dialysis, video-based application (Eulerian), fluorescence angiography, near infrared spectroscopy (NIRS), contrastenhanced duplex. Of these, implantable arterial Doppler have recent and wide set of data showing efficacy, less false-positive and less flow variability [51,52]. NIRS on the other side, based on the differential absorption of light by regional oxygenated and not oxygenated haemoglobin, has the advantage to be non-invasive, cheap, reliable and reproducible. In different studies, authors reported how regional oxygen saturation drops before the flap colour modified, improving salvage rates and decreasingflaplosses [52,53].

Mobilization and DVT prophylaxis
Data on early mobilization come from studies in major abdominal procedures but few retrospective cohort studies evidenced how early mobilization removal of drains, urinary and epidural catheter (since day 2), in head and neck and plastic reconstructive surgery is associated with fewer pulmonary complications [54,55]. For head and neck patients, early execution of speech and swallowing exercises should be respectively started since day 2 and 4 after surgery [56]. Different authors recommend for all microsurgery patients a venous thrombosis prophylaxis since 6 h after surgery but, in presence of an history of previous thrombosis or in presence of high score for macrovascular thrombosis [Caprini score is one of most valid in plastic reconstructive surgery (Figure 3)] a prompt referral to the haematology team should be considered [57,58].

Conclusion
Microvascular surgery is among the best and advanced options for reconstruction in head and neck and breast fragile cancer patients.
Anaesthetic management in these settings clearly affects the outcome and flap viability; however, evidences of standard care are still under investigation. Main areas of controversy involve the need to develop standard multidisciplinary ERAS protocols, as well as standard perioperative management pathways [59,60]. As discussed in this paper, the main fields of research and debate for anaesthetists currently are: pre-operative risk stratification, CO monitoring and hemodynamic intraoperative target limits, ITU admission indications, early extubation, mobilization protocols and pain management strategies. The necessity to embed anaesthetists in new standard multidisciplinary recovery pathways makes their role as "perioperative doctors" extremely challenging and the understanding conveyed in this paper will guide future studies [20].