Abstract complications such as flap hypo-perfusion. In this systematic

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Last updated: October 20, 2019

Abstract  Background: anaesthetic management for microvascularreconstructive surgery is challenging and clearly effects the risk of majorcomplications such as flap hypo-perfusion. In thissystematic review we explore recent (last 7 years) clinical evidences relatedto perioperative management and anaesthetic controversy of patients undergoing microvascularreconstructive surgery, especially focused on head and neck surgery with freeflaps (FF) and breast reconstructive surgery with deep inferior epigastricperforator flap (DIEP-flap).Methods: a literature search of published clinical studies between 2011 and2018 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 3groups: preoperative-intraoperative-postoperative anaesthetic management andareas of controversy for patients undergoing head and neck surgery with FF andbreast reconstructive surgery with DIEP-flap. Discussion: anaesthetic management for flap reconstructivesurgery remains an open field of interestwith limited evidences regarding a standard care. Main components of researchcurrently are: the need to join standard multidisciplinary enhanced recoverypathways, as well as the necessity to develop a standard intraoperativemanagement. In theatre, the recent hemodynamic parameter “HypotensionProbability Indicator” (HPI) is promising: the advantage to predict a drop inthe mean arterial pressure can be more effective than a fluid therapy titratedto maintain SVV less than 13%. Prospective studies are necessary to clarify.  Key words: flap reconstructive surgery, anaesthetic management, perioperativemanagement  CorrespondingAuthor: M.

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P. Lauretta, Via A. Bassini 18, 00047Marino (Rome) Italy. [email protected]       Introduction Microvascularflap surgery is one of the best and fine options for reconstruction in head andneck cancer patients, plastic, trauma and burns (1).Anaestheticmanagement in these settings has limited evidences of standard care and clearlyaffects the outcome, with high impact on flap survival.

Main areas ofcontroversy for anaesthesiologist involve the need to take part into standard multidisciplinaryenhanced recovery after surgery protocols (ERAS protocols), as well as astandard perioperative management, especially in terms of pre-operative assessment,hemodynamic monitoring, goal-directed fluid therapy, thermoregulation, flapmonitoring, deep vein thrombosis (DVT) prophylaxis, intensive therapy unit admission(ITU), early mobilization, antibiotics guidelines, analgesia (2).  Methods Two medical database Pubmed and Medline were queried, accordingwith Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA) recommendations (3). The methodological features of thisanalytic review have been registered and accepted into the InternationalProspective Register Of Systematic Review (PROSPERO) database (registrationnumber: CRD42018082433) (4).

Key wordsused for literature search were: -“Intraoperative management for free flapsurgery” – “Anaesthetic management for microvascular reconstructive surgery” –”Perioperative management for microvascular surgery” – “Anaesthetic assessmentfor flap reconstructive surgery”- “Anaesthesia for head and neck reconstructivesurgery” – “Anaesthesia for plastic reconstructive surgery”- “ERAS protocols formicrovascular reconstructive surgery” -“Haemodynamic monitoring in flapreconstructive surgery” – “Goal-directed therapy for reconstructive surgery” -“Blood loss management in reconstructive flap surgery” – “Postoperative carefor flap reconstructive surgery”. Completed studies published in peer-reviewedjournals between January 2011 and January 2018 were considered to be eligibleand abstracts were excluded. The search criteria for inclusion in this reviewwere: language (English), study type (human, clinical article, clinical trial,controlled clinical trial, controlled study, randomized controlled trials, casereport, cohort studies, institutional surveys), type of surgery (head and neck reconstructionswith FF and plastic breast reconstructions with DIEP flap). Authorsindependently screened and assessed the titles, abstracts, and the full-textarticles.  Results A total of4307 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):  1.    preoperative anaesthetic management and areas ofcontroversy for patients undergoing microvascular reconstructive surgery 2.    Intraoperative anaesthetic management and areas ofcontroversy for patients undergoing microvascular reconstructive surgery 3.    Postoperative anaesthetic management and areas ofcontroversy for patients undergoing microvascular reconstructive surgery          Figure 1. Flowchart of identification of papers included in systematic review.    Preoperative anaesthetic management and areasof controversy for patients undergoing microvascular reconstructive surgery  RiskStratification Patientspresenting for head and neck FFs surgery and breast reconstructive surgery arefragile 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, clinicalcharacteristics also contribute to flap failure (7).

The Division of Plasticand Reconstructive Surgery, University of Southern California, investigated anumber of non-technical variable in 2015, using the American College ofSurgeons’ National Surgical Quality Improvement Program (NSQIP) database. Univariateanalysis was conducted to determine the association of FF failure with theindividual factors: age, gender, ethnicity, body mass index, intraoperativetransfusion, diabetes, smoking, alcohol, American Society of Anaesthesiologistsclassification, year of operation, operative time, number of flaps, and type ofreconstruction. Flap loss rate was 4.4%. Operative time was the onlysignificant independent risk factor, as resulted from the multivariate logisticregression (8). According the analysis conducted by anotherplastic unit in Istanbul, patient’s age was not an independent variable forincreased risk in microvascular reconstruction. However, operative time and reconstructionsites were associated with higher incidence of complications and ITU admissions(9).

Another important study, held in Toronto in 2016, recognizedoperative time and smoking as the independent risk factors for intraoperative complicationsin reconstructive breast flap surgery (10).  Several preoperative investigations playa role in the risk stratification of these patients. Studies revealed how cardiopulmonaryexercise testing (CPET) in complex patients is pivotal to assess the functionalcapacity. Many institutions routinely use CPET to design the operation and toinform patients about risks and benefits of surgery (11). In conclusion, flapischemia is a multifactorial event and, according recent literature,demographics and medical patient’s characteristics such as: age, ethnicity, radiation,chemotherapy, medical comorbidities, smoking, are not independent risk factors.Preoperatively, patients need to be assessed to ensure the best perioperative managementbut intraoperative management and technical variables may have higher importancefor the outcome (12).

 Nutrition, preoperativefasting and preoperative education  Accordingrecent 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 patientseligible for oral intake, clear solids should be allowed up to 2 hours andclear fluids up to 6 hours before anaesthesia. (14, 15).  All patients undergoing major head andneck cancer surgery with FFs and breast reconstructive surgery should beadequately prepared regarding the surgical journey and evidences suggest theyshould receive a systematic teaching. If anaesthetists and qualified healthprofessionals should share this discussion, is still not clarified, due toshortage of specifically focused trials (16). In conclusion, theimplementation of a multidisciplinary pre-operative evaluation driven by anaesthetists,nutritionists, other medical specialists and health practitioners may reduce post-operativecomplications derived from pre-existing conditions (17).

                   Intraoperative anaesthetic management andareas of controversy for patients undergoing microvascularreconstructive surgery   As wehighlighted in the previous chapter, intraoperative management has greatinfluence for the surgical outcome and the anaesthetist plays a pivotal role(12).   Fluidmanagement  Different studies, demonstratedthe predictive relationship between the quantity of intraoperative fluid administratedand the rate of postoperative complications in FF surgery (18, 19). From theanalysis on 154 patients with head and neck reconstructions with fibular FFs, fluidvolume higher than 5500 ml was associated with an increase in medical and surgicalcomplications, and a cut-off value of 7000 ml was identified as the onlysignificant risk factor for major complications (19). FFs don’t present lymphaticdrainage, therefore, every anaesthesiologist needs to consider these characteristicsin order to maintain intravascular blood volume, prevent flap oedema and thepro-coagulant state due to rapid administration of crystalloids (20). Regardingthe use of colloids, data have shown that volume higher than 20-30 ml/kg/24 h canincrease perioperative morbidity, and Hydroxyethyl starch seems more promisingto expand plasma volume and reduce blood viscosity if compared togelatine-based colloids (21). Everypatient 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 goal-directedfluid therapy, titrated to keep SVV ?13%, with the use of mini invasivearterial pulse contour device, results in improved oxygen delivery and reducesthe intravenous fluid administration, with better outcomes (22).

We’ll discuss later on in this paper, other detailsregarding hemodynamic monitoring. Haemoglobin  Haemoglobin target is a sliding value in head and neck andplastic 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). Evenif flap perfusion and peripheral oxygen delivery is a priority, several observational studies in head andneck cancer have highlighted how allogenic blood transfusion is associated withhigher rate of postoperative complications and worse prognosis, andanaesthesiologist usually follow blood conservation strategies in high-riskpatients (23).   Blood Pressure(BP) management BP management, again, is notwell standardised in this type of surgery, and enhancement of flap perfusion intheatre is always a priority. The use of vasopressors in FFs surgery is amatter of controversy.

Evidence from animal models have revealed that the useof vasopressors leads to vasoconstriction in the microcirculation of the flap,however, this has not been shown in the clinical settings (24). Accordingdifferent clinical studies, a general intraoperative well recognised target formean arterial blood pressure (MAP) during anastomosis is a value equal or majorthan 70 mmHg, while a MAP lower than 60 mmHg is considered “hypotension” (25). Dobutamine and vasoconstrictorscan be safely used if the goals for BP and CI are not achieved withSVV<10-13% (26-28).   no de?nitive consensus hasbeen reached regarding optimal ?uid protocols for patientsundergoing head and neck reconstruction with microvascu-lar free tissu e transfer.no de?nitive consensus hasbeen reached regarding optimal ?uid protocols for patientsundergoing head and neck reconstruction with microvascu-lar free tissu e transfer.no de?nitive consensus hasbeen reached regarding optimal ?uid protocols for patientsundergoing head and neck reconstruction with microvascu-lar free tissu e transfer.no de?nitive consensus hasbeen reached regarding optimal ?uid protocols for patientsundergoing head and neck reconstruction with microvascu-lar free tissu e transfer.

no de?nitive consensus hasbeen reached regarding optimal ?uid protocols for patientsundergoing head and neck reconstruction with microvascu-lar free tissu e transGlycaemiccontrol Stress hyperglycaemiais a very common feature of complex patients: targets and relationships withoutcome are not clear, with contrasting results from literature (29). Authorsfrom the national survey in UK evidenced how the majority of anaesthesiologist,involved in head and neck FFs reconstructions, would intraoperatively commencean insulin infusion at a blood sugar level of 10–12 mmol/l, a minority of themwould use a slightly higher trigger of 12–14 mmol/l (21). The tight and fashinating link between insulin and the brain, with discernibleeffects on memory, learning abilities, and motor functions in fragile patientshas been widely explored in literature by a number of authors (30).    Type ofAnaesthesiaOnlyfew studies, evaluate the impact of anaesthesia management in microvascularreconstructive surgery. One of these, recently recorded the differences betweenpatients who received inhalation and total intravenous anaesthesia (TIVA) in FFsurgery (31). Patients in the TIVA group required less perioperativefluids (both crystalloid and colloid) to maintain hemodynamic stability,furthermore, after multivariate regression, patients in the TIVA group had asignificantly reduced risk of pulmonary complication compared with theinhalation group. Some anaesthetist may be concerned about the possibility ofmetabolic acidosis -propofol infusion syndrome (PRIS)- which would cause damageto a fresh anastomosis in flaps.

The association between PRIS and propofol infusionis demonstrated only for doses higher than 4 mg/kg/h when the duration lastslonger than 48 h (32). Moreover, as part of a good anaesthetic strategy, patientsundergoing head and neck or plastic cancer surgery should always receiveintraoperative medications to mitigate postoperative nausea and/or vomiting(PONV) and a combination of corticosteroid and antiemetic is always indicated (33).? Antibiotics Many patients undergoing FFs surgery have a number of riskfactors potentially able to trigger postoperative infections (alcohol, smokingabuse, radiation, chemotherapy, poor nutritional status, long operation time).In this setting, antibiotic prophylaxis is still under debate and every centrehave specific protocols. From a number of international studies, the choice ofantibiotic appears to affect the incidence of postoperative infections and flapsite infections more than the duration (34, 35). From a number of evidence ampicillin-sulbactamor cefuroxime are the preferred prophylactic antibiotic for majorclean-contaminated head and neck procedures, less than or equal to 24 hours of antibiotic 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(34, 36, 37).

  IntraoperativeMonitoring Again as a result form the UK nationalsurvey, in theatre, a number of anaesthesiologists use additional monitoringincluding: 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 cathetercorrelates well with pulmonary artery thermistors (21, 38).Recentguidelines suggest that hemodynamic monitoring should be used in high riskpatients undergoing major surgery to enhance fluid optimisation, reduce mortality,morbidity and reduce costs. Flo/Trac Vigileo system, based on arterial waveformanalysis, and patient’s age, sex, height, weight is often used in FF reconstructivesurgery as mini invasive and reliable (39). As additional parameter, the recent “Hypotension ProbabilityIndicator” (HPI) could be promising: the advantage to predict a drop in themean arterial pressure, before hypotension occurs, can be more effective than a fluidtherapy titrated to maintain SVV less than 13% (40). Prospective studies arerequired to investigate the relationship between HPI and flap perfusion intheatre -Figure 2- (41).  Figure 2. Hypotension probability indicator(HPI).

                                                                                (From http://www.edwards.com/gb/devices/decision-software/hpi)Postoperative anaesthetic management andareas of controversy for patients undergoing microvascular reconstructivesurgery  ITU admission  A number of recent studies support that uncomplicated FFspatients may be safely assisted outside ITU (42, 43).

Panwar et al. recently,with an interesting cohort study, tried to understand if postoperativemanagement in ITU is necessary. Ninety-nine patients were included in thehistorical cohort of ITU patients, and 157 patients were enrolled in theprospective arm after creation of a head and neck surgical unit. They noted nosignificant changes in flap survival, inpatient morbidity, or mortality. Theydid, however, note a significant 1-day reduction of hospitalization and areduction in total costs (42,43). From an interesting survey held in USA, nurses employed in an academic medical center and nurses with morethan 5 years of experience were significantly more comfortable with theirability to care for microsurgical patients (44). Ideally, uncomplicatedpatients receiving microvascular surgery should be stepdown in high-dependency units or equipped specialized surgical units, however, the pivotal role of nursing and health practitioner staff cannotbe underestimated, such as their workload. Early postoperative extubation and tracheostomy  Airwaymanagement in patients undergoing major head and neck procedures with FFsreconstruction includes the protection of the airway if bleeding, swelling and oedemaoccur.

Surgical tracheotomy has rare severe complications but presents the dangerto prolong the hospital stay. According the last indications of ERAS protocols, the decision to perform atracheotomy is now linked to the presence of specific conditions such asadvanced cancer stage and location, otherwise, early extubation is alwayspreferred (45). Early feeding  Recent recommendations supportearly re-entrance of enteral nutrition in head and neck FFs and DIEP-flapreconstructive surgery (46, 47). However, for head and neck patients,considerations as risk of wound dehiscence, fistula, and aspiration must bedone. Recent studies compared early (prior to postoperative day 6)and late oral intake groups (postoperative day 6 or late) and the “early” groupwas not linked to any increased morbidity or adverse outcome, at the same time,duration of hospital stay was lower (48, 49). Enteralfeeding 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 nonsteroidalanti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors (COX inhibitors), and paracetamol, is safe,effective, able to reduce narcotic side effects and to facilitate rapid recoveryafter surgery: when this approach is not sufficient, patient controlledanalgesia (PCA)can be eligible (50). For plastic reconstructive surgery with DIEP-flaps, additionalnerve blocks can be considered, such as the transversus abdominal plane block(TAP block), while small catheter injecting local anaesthetics can be promisingin a number of head and neck reconstruction such as FFs with fibular harvest (51,52).

 Flap perfusion monitoring  Postoperatively, a number of different instruments are accountable toassess flap perfusion and viability including: Doppler, implantableDoppler, micro-dialysis, video-based application (Eulerian), fluorescenceangiography, near infrared spectroscopy (NIRS), contrast-enhanced duplex. Ofthese, implantable arterial Doppler have recent and wide set of data showing efficacy,less false-positive and less flow variability (53, 54). NIRS on the other side,based on the differential absorption of light by regional oxygenated and notoxygenated haemoglobin, has the advantage to be non-invasive, cheap, reliableand reproducible. In different studies, authors reported how regional oxygensaturation drops before the flap colour modified, improvingsalvage rates and decreasing flap losses(54, 55).  Mobilization & DVT prophylaxis  Data on early mobilizationcome from studies in major abdominal procedures but few retrospective cohortstudies evidencedhow early mobilization (since day 1) withearly removal of drains, urinary and epidural catheter (sinceday 2), in head and neck and plastic reconstructive surgery is associatedwith fewer pulmonary complications (56, 57). For head and neck patients, earlyexecution of speech and swallowing exercises should be respectively started sinceday 2 and 4 after surgery (58).

Different authors recommend for allmicrosurgery patients a venous thrombosis prophylaxis since 6 h after surgerybut, in presence of an history of previous thrombosis or in presence of highscore for macrovascular thrombosis (Caprini score is one of most valid inplastic reconstructive surgery -Figure3-) a prompt referral to the haematology team should be considered (59, 60).                         Figure 3. Caprini Score & algorithm. Conclusion  Microvascularsurgery is among the best and advanced options for reconstruction in head andneck and breast fragile cancer patients.

Anaestheticmanagement in these settings clearly affects the outcome and flap viability,however, evidences of standard care are still under investigation. Main areasof controversy involve the need to develop standard multidisciplinary ERASprotocols, as well as standard perioperative management pathways (61, 62). Asdiscussed in this paper, the main fields of research and debate foranaesthetists currently are: pre-operative risk stratification, CO monitoringand hemodynamic intraoperative target limits, ITU admission indications, early extubation,mobilization protocols and pain management strategies. The necessity to embedanaesthetists in new standard multidisciplinary recovery pathways makes theirrole as “perioperative doctors” extremely challenging and the understandingconveyed in this paper will guide future studies (21).   Authors’Note Authors solely contributed to this article andassume full responsibility for the content of the article.

 Declarationof Conflicting Interests The author(s) declared no potential conflicts ofinterest with respect to the research, authorship, and/or publication of thisarticle.  Funding The author(s) received no financial support for theresearch, authorship, and/or publication of this article.

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