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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 76-79

Effect of intraoperative vasopressor use on free flap outcome following major head-and-neck reconstructive surgeries


Department of Anaesthesia, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

Date of Submission02-Nov-2020
Date of Decision05-Nov-2020
Date of Acceptance07-Nov-2020
Date of Web Publication8-Dec-2020

Correspondence Address:
Sunil Rajan
Department of Anaesthesia, Amrita Institute of Medical Sciences, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhnps.jhnps_53_20

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  Abstract 


Introduction: Major head-and-neck surgeries involving wide excision of the tumor usually necessitate reconstruction with free flaps for tissue cover. Even with meticulous fluid management with crystalloids, colloids, albumin, blood, and blood products, many patients become hemodynamically unstable and require the use of vasopressors perioperatively. Objectives: The purpose of this analysis was to assess the safety, role, and present-day trends of the use of vasopressor agents in free flap surgeries and to find any relation of graft rejection or failure of flap surgeries or postoperative complications with perioperative use of such agents. Methods: Reviewing the literature regarding the usage of vasopressors in head-and-neck free flap surgeries, percentage of flap survival, thrombosis of the artery, venous edema, and need for revision surgery were analyzed. Most of the published data had shown that optimizing hemodynamic stability with vasopressors had a more beneficial effect on overall flap perfusion and minimized the complications of iatrogenic fluid overload. The common conclusion was that perioperative vasopressor administration was not detrimental to free flap survival. Conclusion: Based on available data, it is concluded that perioperative use of vasopressors does not adversely affect free flap outcome in patients undergoing head-and-neck reconstructive surgeries and could even be beneficial considering the avoidance of complications of liberal intravenous fluid administration.

Keywords: Free flap, head and neck, perioperative, reconstruction, vasopressor


How to cite this article:
Rajan S, Babu KC, Tosh P. Effect of intraoperative vasopressor use on free flap outcome following major head-and-neck reconstructive surgeries. J Head Neck Physicians Surg 2020;8:76-9

How to cite this URL:
Rajan S, Babu KC, Tosh P. Effect of intraoperative vasopressor use on free flap outcome following major head-and-neck reconstructive surgeries. J Head Neck Physicians Surg [serial online] 2020 [cited 2021 Apr 18];8:76-9. Available from: https://www.jhnps.org/text.asp?2020/8/2/76/302635




  Introduction Top


Major head-and-neck surgeries involving wide excision of the tumor usually necessitate reconstruction with free flaps for tissue cover. Advances in anesthesia and surgical techniques have led to excellent surgical outcome of >95% in patients undergoing head-and-neck free flap reconstruction. These surgeries are very often associated with major blood loss. Even with meticulous fluid management with crystalloids, colloids, albumin, blood, and blood products, many patients become hemodynamically unstable and require the use of vasopressors perioperatively.

The safety of vasopressors during free flap surgeries is still a topic of debate among surgeons and anesthesiologists. The main argument against vasopressor use is chances of vasospasm and reduced perfusion which can lead to loss of flap. However, these drugs are often essential and form part of protocols to maintain hemodynamics and postoperative recovery. Vasopressors also help in decreasing the intraoperative and postoperative fluid overload leading to tissue edema and pulmonary complication. Tissue edema itself can impede flap perfusion.

Objectives

The purpose of this analysis was to assess the safety, role, and present-day trends of the use of vasopressor agents in free flap surgeries and to find any relation of graft rejection or failure of flap surgeries or postoperative complications with perioperative use of such agents.


  Methods Top


Reviewing the literature regarding the usage of vasopressors in head-and-neck free flap surgeries, percentage of flap survival, thrombosis of the artery, venous edema, and need for revision surgery were analyzed. Literature that was selected for reviewing was searched with terms such as vasopressors, microvascular free flap, and head-and-neck reconstructions. Case reports and case series were excluded.

Vasopressors in common use perioperatively

Noradrenaline

It is also called norepinephrine and its predominant use is as a peripheral vasoconstrictor. The starting dose is 0.025 mg/kg/min and dose is escalated based on response. At low doses of <2 mcg/min, the beta-1 effects may be more pronounced and potentially cardiac output. However, in doses >3 mcg/min, the alpha-1 effects will predominate resulting in vasoconstriction and dose-dependent increases in systemic vascular resistance. It can cause reflex bradycardia and excessive vasoconstriction can produce decreased end-organ perfusion, especially when infusion of norepinephrine is used without appropriately treating hypovolemia.[1],[2],[3],[4]

Dopamine

It is indicated in symptomatic bradycardia unresponsive to atropine or pacing and hypotension with systolic blood pressure <70 mmHg with signs and symptoms of shock. Dosage is 2–20 mcg/kg/min. Common adverse effects are severe hypertension (especially in patients taking nonselective b-blockers), ventricular arrhythmias, cardiac ischemia, and tissue ischemia/gangrene (high doses or due to tissue extravasation).[5]

Dobutamine

It is commonly used in low cardiac output conditions (decompensated heart failure, cardiogenic shock, and sepsis-induced myocardial dysfunction), symptomatic bradycardia unresponsive to atropine, or pacing in doses 2.5–10 mcg/kg/min. Side effects are tachycardia, increased ventricular response rate in patients with ventricular arrhythmias, atrial fibrillation, ventricular arrhythmias, cardiac ischemia, severe hypertension resulting in cerebrovascular hemorrhage, sudden cardiac death, hypertension (especially nonselective b-blocker patients), and hypotension.[5]

Vasopressin

It is mainly indicated in shock (vasodilatory and cardiogenic) and cardiac arrest. Adverse effects include arrhythmias, hypertension, decreased cardiac output (at doses >0.4 U/min), cardiac ischemia, severe peripheral vasoconstriction causing ischemia (especially skin), and splanchnic vasoconstriction.[5]

Adrenaline

It is indicated in cardiac arrest: ventricular fibrillation, pulseless ventricular tachycardia, asystole, pulseless electrical activity, and also in symptomatic bradycardia, severe hypotension, anaphylaxis, and severe allergic reactions. Dosage is 0.04–0.4 mcg/kg/min. Side effects include ventricular arrhythmias, severe hypertension resulting in cerebrovascular hemorrhage, cardiac ischemia, and sudden cardiac death.[5]

Literature review

In most of the published data, vasopressors were used in the range of 53%–88% and the flap failure varied from 1.48% to 13.1% and found no difference in flap failure between vasopressor and nonvasopressor groups. Fang et al.[6] studied 2983 patients who had undergone flap surgeries and found that vasopressor use was not associated with flap failures. Harris et al.[7] had also made similar findings. However, Chang et al.[8] observed that perioperative vasopressor use increased the risk of arterial complications in flap surgeries.

Dosage and timing of vasopressor use could also influence free flap outcome. Timing of use such as during or after flap harvesting could have varying effects. Chan et al.[9] had shown that no relationship existed between timing of vasopressor administration and flap failures. A study by Harris et al. also has made similar observations where the effect of the drug during the first 3 h and last 3 h and during the time in between was taken into account.[7]

Another retrospective analysis on 120 patients had shown that perioperative use of noradrenaline to maintain blood pressure did not adversely affect free flap outcome in patients who underwent head-and-neck reconstructive surgeries with free flap. They had observed that re-exploration rate was marginally increased with the use of noradrenaline, however, the final flap outcome remained unaffected. The dose of noradrenaline used varied from 0.02 to 2 mg/kg/min.[10] Kelly et al. made a retrospective review on the impact of intraoperative vasopressor use in free tissue transfer during the head, neck, and extremity reconstruction. They observed that the frequency of vasopressor use was 53.2% with no significant difference in flap outcome with and without the use of vasopressors.[11]

A randomized controlled trial in patients undergoing ablative and reconstructive head-and-neck surgery with microvascular flap also showed the effectiveness and safety of noradrenaline in the postoperative period to maintain mean arterial pressure between 80 and 90 mmHg. In the study, normovolemia was maintained and flap perfusion was monitored with continuous tissue partial pressure of oxygen and microdialysate metabolite (lactate-to-pyruvate ratio) measurements.[12]

Fang et al. assessed the effect of intraoperative use of phenylephrine, ephedrine, or calcium chloride as an intravenous bolus and found that it did not increase flap compromise and failure rates in cancer patients.[6] The effect of dobutamine on perfusion of free flaps during head-and-neck reconstructive surgery had shown that both mean and maximum blood flows were increased significantly in the anastomosed artery with the use of dobutamine infusions at 4 and 6/mg/kg/min which led to increased cardiac output and improved free flap perfusion.[13] The intraoperative use of vasopressors such as ephedrine, phenylephrine, or both was found to be safe in free jejunal free flap reconstruction surgeries for reconstruction of circumferential pharyngeal defects following resection of malignancies of the hypopharynx.[9]

Monroe et al. analyzed data of 169 patients who had undergone free flap surgeries. Flap survival was found to be 96.5%. A total of 139 (82%) patients had received vasopressors intraoperatively. They found that intraoperative use of vasopressors did not appear to increase overall flap failure and the incidence of complications. They concluded that intraoperative vasopressor use in free flap surgery was not be considered as harmful as previously feared.[14] A systematic review and meta-analysis of 14 studies representing 8653 cases by Goh et al. stated that vasopressors were associated with less total flap failure overall and less pedicle thrombosis in head-and-neck reconstruction specifically. They were of the opinion that optimizing hemodynamic stability with vasopressors had a more beneficial effect on overall flap perfusion and minimized the complications of iatrogenic fluid overload and concluded that perioperative vasopressor administration was not detrimental to free flap survival.[15]

Data of 933 patients undergoing head-and-neck free flap reconstruction were analyzed from 4 cohort studies with and without intraoperative vasopressor administration. The meta-analysis demonstrated no statistically significant difference in the incidence of flap failure (2.9 vs. 3.6%) or incidence of flap complications (16.8 vs. 18.6%). Based on the evidence, Swanson et al. concluded that intraoperative use of vasopressors had no impact on the incidence of flap failure or flap complications.[16] Similar observations and recommendations were made by Naik et al. also.[17]

Knackstedt et al. had analyzed 4 prospective and 6 retrospective studies yielding 6321 patients and 7526 flaps. There were 15.9% failures in the vasopressor group and 26.8% failures in the nonvasopressor group. Their results suggested that vasopressor utilization did not directly result in increased complications. Flaps that received vasopressors had a statistically lower rate of take back and failure.[18]


  Discussion Top


During free flap reconstruction, the flow across anastomoses primarily depends on perfusion pressure and also on blood viscosity to some extent. General anesthesia can cause an increase in blood viscosity, red cell aggregation, fibrinogen, clotting factors, platelet aggregation and adhesion, and impaired fibrinolysis leading to impaired perfusion in microcirculation. Hemodilution decreases viscosity, thereby increasing blood flow which has led to the traditional practice of hypervolemic hemodilution and avoidance of vasoconstrictors during free flap surgeries. However, intravascular fluid expansion using crystalloids can lead to extravasation into the interstitial spaces and result in local as well as generalized edema. As free flaps lack intact lymphatic drainage, they are very sensitive to extravasation of fluids and pressure effects compromising flap perfusion.[19],[20] Therefore, the use of vasopressors intraoperatively can improve the flap perfusion secondary to elevated mean arterial pressure. Moreover, restricted use of intravenous fluids could be beneficial due to reduction in tissue edema.

Adrenergic innervation of vasculature is responsible for vasoconstriction of arterioles and precapillary sphincters in response to sympathetic stimulation. During free flap harvest, local catecholamine is released due to activation of sympathetic fibers during tissue dissection. However, once flap gets denervated, it does not respond in the same manner as the rest of the body. Hence, the vasoconstrictive response of denervated recipient vessels to sympathetic stimulation is questionable.

Spectral analysis of laser Doppler blood flow signals has demonstrated denervation of free flaps in patients who had undergone head-and-neck cancer resection with free flap reconstruction. It was shown that with the use of norepinephrine, control of blood flow shifted toward low-frequency vasomotion where blood flow depended mostly on an average blood pressure. Therefore, noradrenaline was recommended as the most suitable agent following free flap reconstructive surgeries of the head-and-neck malignancy patients.[21]

The common causes of flap failure are multifactorial such as arterial (arterial thrombosis and vasospasm), venous (venous thrombosis, vasospasm, and mechanical compression), flap edema (excessive use of crystalloids and excessive hemodilution), generalized vasoconstriction (hypothermia, pain, and respiratory alkalosis), hypotension (hypovolemia and use of myocardial depressants), and prolonged ischemia of the flap.[22] Therefore, meticulous attention to each contributory factor and timely intervention will yield an optimal patient outcome.


  Conclusion Top


Based on available data, it is concluded that perioperative use of vasopressors does not adversely affect free flap outcome in patients undergoing head-and-neck reconstructive surgeries and could even be beneficial considering the avoidance of complications of liberal intravenous fluid administration.

Disclosure

This material has never been published and is not currently under evaluation in any other peer-reviewed publication.

Ethical approval

The permission was taken from the Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Smith MD, Maani CV. Norepinephrine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537259/. [Last accessed on 2020 Nov 01].  Back to cited text no. 1
    
2.
Overgaard CB, Dzavík V. Inotropes and vasopressors: Review of physiology and clinical use in cardiovascular disease. Circulation 2008;118:1047-56.  Back to cited text no. 2
    
3.
Cryer PE. Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med 1980;303:436-44.  Back to cited text no. 3
    
4.
van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, et al. Contemporary management of cardiogenic shock: A scientific statement from the American Heart Association. Circulation 2017;136:e232-68.  Back to cited text no. 4
    
5.
Keith G Allman, Iain H Wilson, Oxford Handbook of Anaesthesia. 4th Edition UK Oxford University Press 2016. p.1197-200.  Back to cited text no. 5
    
6.
Fang L, Liu J, Yu C, Hanasono MM, Zheng G, Yu P. Intraoperative use of vasopressors does not increase the risk of free flap compromise and failure in cancer patients. Ann Surg 2018;268:379-84.  Back to cited text no. 6
    
7.
Harris L, Goldstein D, Hofer S, Gilbert R. Impact of vasopressors on outcomes in head and neck free tissue transfer. Microsurgery 2012;32:15-9.  Back to cited text no. 7
    
8.
Chang CS, Chu MW, Nelson JA, Basta M, Gerety P, Kanchwala SK, et al. Complications and cost analysis of intraoperative arterial complications in head and neck free flap reconstruction. J Reconstr Microsurg 2017;33:318-27.  Back to cited text no. 8
    
9.
Chan JY, Chow VL, Liu LH. Safety of intra-operative vasopressor in free jejunal flap reconstruction. Microsurgery 2013;33:358-61.  Back to cited text no. 9
    
10.
Rajan S, Sudevan M, Kadapamannil D, Mohan A, Paul J, Kumar L. Does perioperative use of noradrenaline affect free flap outcome following reconstructive microvascular surgeries? A retrospective analysis. Anesth Essays Res 2019;13:79-83.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Kelly DA, Reynolds M, Crantford C, Pestana IA. Impact of intraoperative vasopressor use in free tissue transfer for head, neck, and extremity reconstruction. Ann Plast Surg 2014;72:S135-8.  Back to cited text no. 11
    
12.
Raittinen L, Kääriäinen MT, Lopez JF, Pukander J, Laranne J. The effect of norepinephrine and dopamine on radial forearm flap partial tissue oxygen pressure and microdialysate metabolite measurements: A randomized controlled trial. Plast Reconstr Surg 2016;137:1016e-23.  Back to cited text no. 12
    
13.
Scholz A, Pugh S, Fardy M, Shafik M, Hall JE. The effect of dobutamine on blood flow of free tissue transfer flaps during head and neck reconstructive surgery. Anaesthesia 2009;64:1089-93.  Back to cited text no. 13
    
14.
Monroe MM, McClelland J, Swide C, Wax MK. Vasopressor use in free tissue transfer surgery. Otolaryngol Head Neck Surg 2010;142:169-73.  Back to cited text no. 14
    
15.
Goh CS, CS, MJ, Song DH, Ooi AS. Perioperative vasopressor use in free flap surgery: A systematic review and meta-analysis. J Reconstr Microsurg 2019;35:529-40.  Back to cited text no. 15
    
16.
Swanson EW, Cheng HT, Susarla SM, Yalanis GC, Lough DM, Johnson O 3rd, et al. Intraoperative use of vasopressors is safe in head and neck free tissue transfer. J Reconstr Microsurg 2016;32:87-93.  Back to cited text no. 16
    
17.
Naik AN, Freeman T, Li MM, Marshall S, Tamaki A, Ozer E, et al. The use of vasopressor agents in free tissue transfer for head and neck reconstruction: Current trends and review of the literature. Front Pharmacol 2020;11:1248.  Back to cited text no. 17
    
18.
Knackstedt R, Gatherwright J, Gurunluoglu R. A literature review and meta‐analysis of outcomes in microsurgical reconstruction using vasopressors. Microsurgery 2019;39:267-75.  Back to cited text no. 18
    
19.
Pushparaj S, Boyce H, Chisholm D. Anesthetic consideration in a postchemotherapy pediatric patient for segmental mandibulectomy with free fibula reconstruction. Curr Anaesth Crit Care 2009;20:18-21.  Back to cited text no. 19
    
20.
Stepanovs J, Ozoliòa A, Rovîte V, Mamaja B, Vanags I. Factors affecting the risk of free flap failure in microvascular surgery. Proc Latvian Acad Sci Sec B 2016;70:356-64.  Back to cited text no. 20
    
21.
Eley KA, Young JD, Watt-Smith SR. Power spectral analysis of the effects of epinephrine, norepinephrine, dobutamine and dopexamine on microcirculation following free tissue transfer. Microsurgery 2013;33:275-81.  Back to cited text no. 21
    
22.
Adams J, Charlton P. Anesthesia for microvascular free tissue transfer. Br J Anaesth (CEPD Reviews) 2003;3:33-7.  Back to cited text no. 22
    




 

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