Perioperative predictors of early surgical revision and flap-related complications after microvascular free tissue transfer in head and neck reconstructions: a retrospective observational series

Abstract

Objectives
The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer.

Materials and methods
Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression.

Results
The administration of diuretics ( p =0.001) as a treatment for perioperative fluid overload and the type of flap ( p =0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload ( p =0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions ( p =0.8) or on flap-related complications (norepinephrine p =0.6, dobutamine p =0.5).

Conclusion
Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications.

Clinical relevance
In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

Full text

ORIGINAL ARTICLE
Perioperative predictors of early surgical revision and flap-related
complications after microvascular free tissue transfer in head
and neck reconstructions: a retrospective observational series
John-Patrik Burkhard
1
&Jelena Pfister
1
&Roland Giger
2
&Markus Huber
3
&Claudia Lädrach
2
&Manuel Waser
2
&
Radu Olariu
4
&Dominique Engel
3
&Lukas M. Löffel
3
&Benoît Schaller
1
&Patrick Y. Wuethrich
3
Received: 12 November 2020 /Accepted: 25 February 2021
#The Author(s) 2021, corrected publication 2021
Abstract
Objectives The aim of this study was to determine the influence of perioperative fluid management and administration of
vasopressors on early surgical revision and flap-related complications in free tissue transfer.
Materials and methods Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities
were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical
complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in
the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision
category was determined using an optimized multiple logistic regression.
Results The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019)
was associated with a higherrisk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-
related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or
on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5).
Conclusion Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In
contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications.
Clinical relevance In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a
targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.
Keywords Fluid overload .Free flap .Vasopressor .Revision surgery
Introduction
Microvascular free tissue transfer is established in the head
and neck area as a safe and reliable technique for
reconstructing a large defect after extensive resection [1].
However, head and neck surgery involving free tissue transfer
is complex and extensive and associated with an increased risk
of complications related to high patient morbidity, resulting to
prolonged hospital stays and higher costs [1–3].
In particular, free flap surgery requires sufficient blood
circulation. Anesthesiologists face the difficult task of main-
taining hemodynamic stability and tissue perfusion using
crystalloids or colloids and the continuous i.v. administration
of vasopressors or inotropes. However, the amount of fluid
administered intraoperatively has been identified as an impor-
tant predictor of poor results in free tissue transfer surgery,
*John-Patrik Burkhard
jp.burkhard@insel.ch
1
Department of Cranio-Maxillofacial Surgery, Inselspital, Bern
University Hospital, University of Bern, CH-3010 Bern, Switzerland
2
Department of Oto-Rhino-Laryngology, Head and Neck Surgery,
Inselspital, Bern University Hospital, University of Bern,
CH-3010 Bern, Switzerland
3
Department of Anaesthesiology and Pain Medicine, Inselspital, Bern
University Hospital, University of Bern, CH-3010 Bern, Switzerland
4
Department of Plastic, Reconstructive and Aesthetic Surgery,
Inselspital, Bern University Hospital, University of Bern,
CH-3010 Bern, Switzerland
https://doi.org/10.1007/s00784-021-03864-1
Clinical Oral Investigations (2021) 25:5541–5550
/ Published online: 8 March 2021
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associated with a higher incidence of local and systemic com-
plications [4–10]. In addition, there is considerable reluctance
to use vasopressors due to hypothetical concerns about re-
duced graft perfusion during or after surgery, which creates
additional limitations for anesthesiologists searching for
evidence-based options for blood pressure control [11].
Various predictors of complications have been proposed,
such as ASA (American Society of Anesthesiologists) physi-
cal status, previous attempted microvascular transplants, sur-
gery duration, and higher tumor stages, but their importance
still remains controversial [1,5,6,9,10,12,13].
The aim of this retrospective analysis was to assess the
impact of intravenous administration of fluid, norepinephrine,
and dobutamine intraoperatively on early surgical revisions
(i.e., within 30 days) and flap-related complications after free
tissue transfer. Furthermore, we aimed to investigate the in-
fluence of compounding factors.
Material and methods
This retrospective observational study reports a consecutive
case series from a single tertiary center. Ethical approval of
this study was provided by the Ethical Committee of the
Canton Bern, Switzerland (KEKBE 2019-01824), on
January 28, 2020, and the need for informed consent was
waived. The study was not registered. It conforms with the
STROBE (Strengthening the Reporting of Observational
Studies in Epidemiology) guidelines.
Study population
We evaluated health-related data of 131 consecutive patients
who received free tissue transfer surgery in the head and neck
area. These included all malignant diseases of the oral cavity
and the facial skin, osteoradionecrosis, and drug-induced
osteonecrosis of the jaw. The patients were manually identi-
fied and selected from the clinic’s internal database. Relevant
information and patient data were extracted from medical re-
cords, including paper charts and anesthetic protocols, and
stored in the clinic database.
Data collection and outcomes
Preoperative data collection included age, sex, type of pathol-
ogy requiring free tissue transfer, and preoperative comorbid-
ity (arterial hypertension, chronic obstructive pulmonary dis-
ease, diabetes mellitus, renal insufficiency, alcohol consump-
tion, and smoking).
Intraoperative parameters included the type of surgical in-
tervention, duration of surgery, flap type (osseous vs. non-
osseous), total intraoperative administration of i.v. fluids
(crystalloids, colloids, and amount of packed red blood cells),
blood loss, and the total amount of vasopressors (norepineph-
rine and dobutamine) continuously administered.
Postoperative parameters included the lowest hemoglobin
value within 5 days after surgery or before the decision for
surgical revision if surgery was needed before postoperative
day 5 (“nadir hemoglobin”), administration of i.v. furosemide
as a treatment of fluid overload (“diuretics”), type of surgical
revisions, and length of hospitalization.
The primary outcome was the incidence of surgical revision
within 30 days after initial free tissue transfer surgery. We chose
30 days as it is expected to be related to the intraoperative and/or
early postoperative management. Surgical revision was defined
as all surgical interventions associated with the free flap transfer
surgery, regardless of localization (donor, recipient, neck, trache-
ostomy, and flap-site), performed in the operating room. Flap-
related complications included flap dehiscence combined with
partial or total flap necrosis and anastomotic insufficiency or
thrombosis. We aimed to identify independent risk factors for
early surgical revision. In addition, we also performed a sub-
analysis of surgical revision in patients who received osseous
or non-osseous free tissue transfer.
Intraoperative management
Standard monitoring consisted of a three-lead-ECG, pulse ox-
imetry, and invasive (cannulation of the radial artery) blood
pressure measurement. Liberal indication was given awake
fiber optic nasal intubation (under continuous administration
of remifentanil) if there was any uncertainty regarding airway
safety. Induction medication consisted of propofol (2–3
mg/kg), fentanyl (1–2μg/kg), and rocuronium (0.6 mg/kg)
and thereafter bladder catheterization.
For the first part of the surgery, anesthesia was maintained
with a combination of propofol and remifentanil until trache-
otomy, followed by a switch to volatile anesthetics in combi-
nation with dexmedetomidine (0.3–0.5 mg/kg/h) and keta-
mine (20 mg bolus followed by 0.3 mg/kg/h), both to be
terminated 30 to 60 min prior to the end of surgery along with
reuptake of propofol and remifentanil as prophylaxis for post-
operative nausea and vomiting.
Hemodynamic management (goal: systolic blood pressure
≥100 mmHg) was mainly carried out with Ringer’s lactate solu-
tion [14]. If the perfusion index of the pulse oximetry curve was
>5 and urine output between 0.3 and 0.5 mL/kg/h, euvolemia
was assumed, and continuous administration of low-dose norepi-
nephrine (0.02–0.05 μg/kg/min) was initiated after consultation
with the lead surgeon. Additional dobutamine (2–4μg/kg/min)
and colloids were initiated, if necessary. The transfusion thresh-
old varied between 70 and 90 g/L hemoglobin.
Usually, a tracheostomy was performed and maintained to
secure the patient’s airway during and after surgery. In the
absence of tracheotomy, patients were extubated using a
staged-extubation kit.
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Postoperative management
All patients were monitored overnight in the intensive care
unit (ICU) before being transferred to the ward. Patients with
non-osseous reconstruction were mobilized immediately, and
those with osseous reconstruction after 5 days, according to
the in-house regimen. For reconstructions within the oral cav-
ity, nutrition was provided exclusively by a nasal or percuta-
neous stomach tube until wound healing was assured. A target
systolic blood pressure above 100 mmHg was defined for
sufficient flap perfusion [14]. Blood pressure drops were treat-
ed accordingly with volume administration (250–500 mL of
crystalloids). Furosemide was administered intravenously
when there were signs of overhydration (dyspnea, ede-
ma, weight gain). Flap control was performed visually
and by Doppler sonography according to internal guide-
lines at defined times.
Statistical analysis
Variables were compared between patients who needed an
early surgical revision and those who did not. Data were
expressed as median with interquartile range for continuous
variables and frequencies for categorical ones. We performed
exploratory landmark analyses for categorical data using the
Fisher’s exact or the chi-square test, and for continuous data
using the Kruskal-Wallis rank-sum test.
Factors were selected a priori based on their potential as-
sociation with postoperative surgical revision and included
alcohol consumption, early postoperative cardiac event,
amount of intraoperative fluid volume (crystalloids, colloids,
blood products) administered (in mL), intraoperative blood
loss (mL), nadir hemoglobin (g/L), duration of surgery
(min), and the total amount of norepinephrine (in μg) and
dobutamine (in mg).
We first applied a univariable logistic regression of each
predictor with the outcome and examined both the crude odds
ratios and the odds ratios adjusted for “age”and “sex”of the
patients. The univariable logistic regressions were followed
by a multiple binary logistic regression model featuring all
potential predictors. Again, crude and adjusted odds ratios
were examined. The assumption of a linear relationship be-
tween the logit of the outcome variable and each continuous
predictor used in this study was tested by creating a regression
model with the logit as outcome and a set of predictors includ-
ing the corresponding continuous predictor, its own natural
logarithm, and an interaction term of each predictor and its
natural logarithm. In all cases, the interaction terms were not
statistically significant. Multicollinearity was examined by
computing the variance inflation factor (VIF) for the
predictors in the full binary logistic regression model.
The corresponding values (from 1.1 to 2.7) suggested
low levels of multicollinearity.
In terms of model selection, a parsimonious model was
chosen with respect to known preoperative and intraoperative
risk factors for a surgical revision due to the limited number of
events and in order to avoid overfitting the regression. A step-
wise backward selection procedure based on the Akaike in-
formation criterion (AIC) was used to identify independent
risk factors for a surgical revision. Preoperative risk factors
not associated with surgical revision in the final regression
model and with a pvalue less than 0.05 were not included.
The logistic regression model selected by the backstepping
algorithm did not include the confounders “age”and “sex.”
We show marginal effect plots for the final regression models
to highlight the impact of each predictor on the outcome: to
compute these plots, the values of a particular can vary while
the other predictors are held constant (e.g., at their baseline
levels or means) and the predicted probabilities of the out-
come can be graphically displayed. In addition, we present
nomograms of the final prediction models, which allow to
estimate the probabilities of the outcome (e.g., probability of
a surgical revision) for any given values of the predictors.
The fit of the multiple logistic regression models was
assessed using the receiver operating characteristic-area under
the curve (ROC-AUC) and an analysis of deviance (deviance
check). A Monte Carlo cross-validation was performed to
assess the predictive power of the two models on independent
data that was not part of the model fitting procedure: the set of
n=131 patients was randomly split into a training set (60% of
all patients) and a test set (40% of all patients). The multiple
logistic regression was subsequently performed using only the
training data, and the computations of the ROC-AUC
were based only on the test data. This procedure was
performed 1000 times, resulting in a distribution of the
ROC-AUC for each model.
Atwo-sidedpless than 0.05 was considered signif-
icant. Analyses were performed using the R statistical
package (R Foundation for Statistical Computing,
Vienna, Austria, version 4.0.0).
Results
We identified 131 consecutive patients who underwent head
and neck free tissue transfer surgery between January 1, 2014,
and September 9, 2019.
Overall, early surgical revisions occurred in 42/131 pa-
tients (32%). There were 5/42 (12%) with a radial forearm,
15/42 (36%) with an anterolateral thigh, 5/42 (12%) with a
superficial iliac artery perforator, and 17/42 (41%) with a fib-
ula free flap transfer (p=0.094). Revision occurred in 17/34
(50%) “osseous”free tissue transfers and in 25/97 (25.7%)
“non-osseous”free tissue transfers (p=0.018). Median time
to revision was 7 days [IQR 2.25–14] (p=0.001), but 9/42
revisions (21%) were performed within 24 h after initial
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surgery. Early surgical revision (42/131) and flap-related com-
plications (25/131) were caused by anastomosis problems
(6/42, 14.3%; 6/25, 24%), bleeding (9/42, 21.4%; 2/25, 8%),
infection (5/42, 11.9%), dehiscence/necrosis (20/42, 47.6%;
14/25, 56% thereof 3 cases total flap necrosis), and seroma
(2/42, 4.8%) respectively.
Patient data
Patients who needed surgical revision were more prone to
have preoperative chronic alcohol consumption (p=0.090),
suffered more often from underlying cardiac diseases
(p=0.007), and had surgeries of longer duration (p=0.033),
increased intraoperative administration of crystalloids
(p=0.023), increased intraoperative blood loss (p=0.049),
and lower postoperative nadir hemoglobin values (p=0.008)
(Table 1). The total intraoperative administration of norepi-
nephrine (256 vs 192 μg, p=0.530) and dobutamine (25 vs 15
mg, p=0.903) did not differ between patients who needed
surgical revision and those who did not (Table 2). In addition,
the total intraoperative administration of norepinephrine (268
vs. 229 μg, p=0.652) and dobutamine (27 vs 16 mg, p=0.663)
did not differ between patients with flap-related complications
and those without.
Factors influencing early surgical revisions
Effect plots are presented in Figs. 1and 2.Regarding
univariable logistic regression analysis, several
parameters influenced early surgical revisions.
Significantly higher revision rates were found for osse-
ous reconstructions (2.88 [1.28, 6.55], p=0.011). In ad-
dition, diuretics (4.16 [1.94, 9.21], p<0.001) and nadir
hemoglobin (0.95 [0.91–0.99], p=0.008) were seen as
predictive values. Neither administration of norepineph-
rine nor administration of dobutamine (p=0.8) could be
detected as a predictor. With regard to the influence of
previous irradiation in the recipient area and the occur-
rence of early surgical revisions, no significance was
shown in comparison to non-irradiated patients (0.40
[0.14–1.02], p=0.055).
Using backstepping multiple logistic regression analyses
(optimized model), the variables “diuretics”(3.9345 [1.7556,
9.1400], p=0.001) and “flap type”(2.9020 [1.1973, 7.1826],
p=0.019) remained significant. The detailed results can be
seen in Table 3.
Factors influencing flap-related complications
We also identified independent factors specifically for flap-
related complications following the similar regression models
in the frame of a subgroup analysis. The following predictors
could be detected in a final optimized model: diuretics (2.6895
[1.0887, 6.8733], p=0.034) and intraoperative fluid adminis-
tration (1.0003 [1.0001, 1.0004], p=0.039). The administra-
tion of vasopressors could not be detected as a predictor. The
detailed results can be seen in Table 3.
Table 1 Baseline and clinical variables and type of pathology
Baseline characteristics All Surgical complications No surgical complications pvalues
n=131 n=42 n=89
Age, median [IQR], y 62.48 [54.76–71.88] 62.99 [56.7–71.89] 62.48 [53.7–71.78] 0.434
Sex 0.559
Male 85 (64.9%) 29 (69%) 56 (62.9%)
Female 46 (35.1%) 13 (31%) 33 (37.1%)
Alcohol use 57 (43.5%) 23 (54.8%) 34 (38.2%) 0.090
Tobacco use 80 (61.1%) 29 (69%) 51 (57.3%) 0.250
Hypertension 49 (37.4%) 14 (33.3%) 35 (39.3%) 0.565
COPD 24 (18.3%) 8 (19%) 16 (18%) 1.000
Diabetes mellitus 13 (9.9%) 5 (11.9%) 8 (6.1%) 0.755
Hemoglobin [g/L] 133 [123–133] 135 [121–141] 133 [123–140] 0.345
CKD classification 0.176
eGFR [mL/min] >90 (G1) 121 (92.4%) 40 (95.2%) 81 (91.0%)
60–89 (G2) 6 (4.6%) 0 (0%) 6 (6.7%)
30–59 (G3) 4 (3.1%) 2 (4.8%) 2 (2.2%)
<30 (G4) 0 (0%) 0 (0%) 0 (0%)
Preoperative radiotherapy 32 (24.4%) 6 (14.3%) 26 (29.2%) 0.256
Abbreviations:CKD chronic kidney disease, COPD chronic obstructive pulmonary disease, eGFR estimated glomerularfiltration rate, IQR interquartile
range, SD standard deviation, yyear
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Table 2 Surgical, intraoperative, and postoperative variables with status early surgical revision
Surgical and intraoperative characteristics All Surgical complications No surgical complications pvalues
n=131 n=42 n=89
Duration of surgery [min] 560 [489–644] 584 [519–701] 554 [480–625] 0.033
Type of reconstruction 0.018
Non-osseous 97 (74.0%) 25 (59.5%) 72 (80.9%)
Osseous 34 (26.0%) 17 (40.5%) 17 (19.1%)
Type of flap 0.094
Radial forearm flap 31 (23.7%) 5 (11.9%) 26 (29.2%)
ALT 49 (37.4%) 15 (35.7%) 34 (38.2%)
SCIP 15 (11.5%) 5 (11.9%) 10 (11.2%)
Dorsalis pedis 1 (0.8%) 0 (0%) 1 (1.1%)
Scapula 1 (0.8%) 0 (0%) 1 (1.1%)
Latissimus dorsi 1 (0.8%) 0 (0%) 1 (1.1%)
Fibula 33 (25.2%) 17 (40.5%) 16 (18.0%)
Blood loss [mL] 600 [400–1000] 725 [500–1125] 600 [400–1000] 0.049
Intraop. i.v. fluid [total in mL] 5411 [4098–7307] 5823 [4573–7976] 4966 [4004–6861] 0.023
Fluid balance [mL] 3574 [705–8263] 3746 [2841–5769] 3542 [2788–4483] 0.314
Norepinephrine [total in μg] 229 [0–810] 256 [19–698] 192 [0–831] 0.530
Dobutamine [total in mg] 16 [0–44] 25 [0–42] 15 [0–44] 0.903
Postop Nadir Hb [g/L] 93 [87–101] 91 [85–94] 95 [88–103] 0.008
Length of hospital stay (days) 12 [10–16] 16 [11–22] 11 [9–14] 0.005
Abbreviations:ALT anterolateral thigh, g/L grams per liter, Hb hemoglobin, kgBW kilograms per body weight, mcg micrograms, mg milligrams, min
minutes, mL milliliters, SCIP superficial circumflex iliac artery perforator
Fig. 1 Marginal effect plots for
the predictors included in the final
model for early surgical revision.
Each plot illustrates the effect of a
particular predictor on the
probability of a revision surgery
while the other predictors are held
constant. For example, panel a
illustrates the probability of a
revision surgery for the two
categories of flap type while the
predictors diuretics and nadir Hb
[g/L] are held constant (at levels
“no”for diuretics and a nadir Hb
level of 94 [g/L]). Abbreviations:
g/L, grams per liter;
Hb, hemoglobin
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Model significance
The final optimized model (for early surgical revision)
selection accuracy was good (ROC-AUC 0.77) and was
also evaluated by the Monte Carlo cross-validation
(ROC-AUC 0.77) for the full model. The predictive
power(intermsofAUC)ofthefinaloptimizedmodel
without adjustment (with the confounders sex and age)
showed the best performance, the AIC of the optimized,
unadjusted model was lower 152 compared to the opti-
mized, adjusted model (155). The increase in pseudo-R-
squared metrics was also very modest (0.224 vs 0.212).
These three observations confirmed that the best model
was the optimized one without adjustment. Based on the
independent variables depicted by the optimized multi-
ple logistic regression model, we developed a nomo-
gram for prediction of the surgical revision (Figs. 3
and 4).
Discussion
This study provides evidence that postoperative fluid overload
calculated on the administration of furosemide is associated
with greater risks of early surgical revision and flap-related
complications. In addition, excessive intraoperative fluid ad-
ministration may increase flap-related complications. In our
study, there was no observed association of early surgical
revision or flap-related complications due to continuous ad-
ministration of vasopressors. Surgical revisions were needed
in 32% of the cases, and the overall failure rate of microvas-
cular reconstructions was 2.29%, which is consistent with the
current literature [15–21]. Furthermore, in around 12.9% of
the revisions, the donor/recipient site, neck dissection site, or
tracheotomy site was affected.
Hemodynamic stability—based on high cardiac output,
normotony, hematocrit between 0.3 and 0.4 l/l, and urine out-
put >1 mL/kg/h—is usually recommended for sufficient tissue
perfusion and is a challenge for free tissue transfer surgery
[22]. Suitable flap perfusion depends not only on vessel diam-
eter, vessel tone, and an intact vessel barrier, but also on ade-
quate perioperative fluid replacement [23–25]. In order to se-
cure and maintain perfusion, the general indication for fluids
or vasopressor administration is made.
Various studies [8,10,11,26,27] report that excessive vol-
ume of intraoperative crystalloids is predictive of postoperative
complications. This is supported in our study, in which the
administration of furosemide because of perioperative fluid
overload was associated with an approximately fourfold in-
crease in the risk of undergoing surgical revision within 30 days
after the initial flap reconstruction [25,28]. Patients with surgi-
cal revision received significantly more fluid intraoperatively
and had greater blood loss with longer duration of surgery, a
parameter albeit not detected as a predictor of revision or flap
failure. More generous administration of fluid inevitably result-
ed in fluid accumulation in the interstitium. This resulted in
tissue edema and suboptimal oxygen supply locally, a situation
which has to be avoided in free tissue transfer. Therefore, the
postoperative administration of furosemide acts against fluid
overload and reduces interstitial edema. Similarly, longer pe-
riods of hypotension showed higher rates of flap failure. Part
of this increased risk may be mediated by the effect of higher
volume substitution in response to hypotension [9]. Both hypo-
tension and large-volume fluid administration may lead to re-
evaluation of the role of vasopressors in free flap reconstruction.
The misconception that the use of vasopressors causes va-
sospasms in the vascular stem―leadingtothrombosis,
Fig. 2 Marginal effect plots for
the predictors included in the final
model for flap-related
complications. Panel aillustrates
the probability of flap-related
complications for the two
categories of diuretics (holding
the amount of intraoperative i.v.
fluid a constant level), whereas
panel billustrates the probability
of flap-related complications as a
function of the amount of
intraoperative i.v. fluid (while
holding diuretics constant at the
level “no”)
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Fig. 3 Nomogram predicting
surgical revision based on the
type of free tissue transfer.
Abbreviations: g/L, grams per
liter; Hb, hemoglobin; mL,
milliliters
Table 3 ARegression models for early surgical revisions. BSub-analysis of flap-related complications using multivariate regression
Dependent variable Univariate Multivariate (full model) Optimized (step. AIC)
n=131 OR 95% CI pvalue OR 95% CI pvalue OR 95% CI pvalue
A
Age at diagnosis (y) 1.01 0.98, 1.04 0.5
Sex (male vs female) 1.31 0.61, 2.94 0.5
Flap type (osseous vs non-osseous) 2.88 1.28, 6.55 0.011 2.9020 1.1973, 7.1826 0.019 2.9020 1.1973, 7.1826 0.019
Surgery duration (min) 1.00 1.00, 1.01 0.057
Alcohol (yes vs no) 1.96 0.93, 4.15 0.075
Diuretics (yes vs no) 4.16 1.94, 9.21 <0.001 3.9345 1.7556, 9.1400 0.001 3.9345 1.7556, 9.1400 0.001
Nadir Hb [g/L] 0.95 0.91, 0.99 0.008 0.9607 0.9163, 1.0042 0.084 0.9607 0.9163, 1.0041 0.084
Intraoperative i.v. fluid input [mL] 1.00 1.00, 1.00 0.091
Blood loss [mL] 1.00 1.00, 1.00 0.053
Norepinephrine [total in μg] 1.00 1.00, 1.00 0.8
Dobutamine [total in mg] 1.00 0.99, 1.02 0.8
Preoperative radiotherapy (yes vs no) 0.40 0.14, 1.02 0.055
B
Age at diagnosis (y) 1.01 0.97, 1.05 0.7
Sex (male vs female) 1.92 0.74, 5.63 0.2
Flap type (osseous vs non-osseous) 1.82 0.70, 4.57 0.2 1.7375 0.6248, 4.6706 0.3
Surgery duration (min) 1.00 1.00, 1.01 0.2
Alcohol (yes vs no) 1.86 0.78, 4.58 0.2
Diuretics (yes vs no) 2.92 1.20, 7.34 0.018 2.4951 0.9905, 6.4794 0.054 2.6895 1.0887, 6.8733 0.034
Nadir Hb [g/L] 0.95 0.90, 1.00 0.031 0.9743 0.9208, 1.0276 0.3
Intraoperative i.v. fluid [mL] 1.00 1.00, 1.00 0.021 1.0001 0.9999, 1.0004 0.3 1.0002 1.0001, 1.0004 0.039
Blood loss [mL] 1.00 1.00, 1.00 0.044 1.0003 0.9991, 1.0015 0.6
Norepinephrine [total in μg] 1.00 1.00, 1.01 0.6
Dobutamine [total in mg] 1.00 0.99, 1.01 0.5
Preoperative radiotherapy (yes vs no) 0.97 0.33, 2.58 >0.9
Abbreviations:AIC Akaike information criterion, CI confidence interval, g/L grams per liter, Hb hemoglobin, i.v. intravenous, mcg micrograms, mg
milligrams, mL milliliters, OR odds ratio
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ischemia, and loss of the free tissue graft [29,30]―is no
longer supported by recent studies [9,31–33]. The intraoper-
ative application of vasoactive substances does not lead to a
significant absolute increase in flap loss, as Monroe et al. [11]
showed in a prospective study with 169 patients who received
a free tissue graft in the head and neck region. To counteract
hypotension induced by vasodilatation, low-dose vasopres-
sors (e.g., norepinephrine 1–2μg/kg/h) can be used instead
of additional fluid administration. Numerous studies were un-
able to detect a negative effect of norepinephrine administra-
tion on the microcirculation [34–37]. These findings suggest
that the use of vasopressors in microsurgery of the head and
neck region is not a risk factor for developing flap-related
complications per se.
To obtain sufficient tissue perfusion and normovolemia,
blood loss and adequate blood transfusion must be considered.
In this series, intraoperative fluid balance was similar be-
tween the groups, despite a significant increase in blood loss
in the group with surgical revision. This illustrates good
intraoperative hemodynamic management. However, as a
low postoperative hemoglobin value was associated with
surgical revision, a more differentiated fluid approach in-
cluding blood transfusion should be considered at an earlier
time point to support tissue oxygenation, rather than only
perfusion.
Increased blood loss up to 1000 mL has been asso-
ciated with higher risk of surgical revision, wound
healing disorders, complication rates up to 27.8%, and
failure rates of 6.5% in free tissue transfer in head and
neck reconstruction [38–40]. Furthermore, low postoper-
ative hemoglobin appears to be a significant predictor of
flap-related complications and may be interpreted as a
predictor of poor general condition, blood loss during
surgery, and impaired oxygen delivery to the surgical
wounds [41]. A hemoglobin value of <110 g/L seems
to be an independent risk factor for postoperative
surgical complications and prolonged hospitalization
[42–44], just as lower values are a significant predictor
of flap failure [45].
Our study confirms that intraoperativeblood loss and lower
postoperative hemoglobin are significantly associated with a
risk of early surgical intervention. The critical hemoglobin
value for blood transfusion in patients undergoing free flap
surgery remains unclear. Kim et al. [39] recommend transfu-
sion at a hemoglobin value lower than 87.5 g/L. Although
blood transfusions have so far been used with great reluctance
in microvascular surgery, recent studies show benefits [39]. A
possible reason for this skepticism might be the resulting fluid
overload, which clearly is a predictor of poor outcome, rather
than blood transfusion per se. However, complications like
flap failure, wound dehiscence, and wound edge necrosis at
the interface of flap and autochthone tissue might signal a
perfusion deficiency in the flap, whereas donor site seroma
and tracheostoma bleeding are not related to flap perfusion
problems.
This study is limited due to the patient population. To ver-
ify these results, prospective, controlled studies with higher
patient numbers are necessary.
In order to integrate the central result of this study in clinical
routine, the cooperation of surgeons and anesthesiologists
performing free tissue transfers in head and neck surgery is of
great importance. Balanced fluid administration perioperatively,
avoiding persistently low hemoglobin values, and a targeted use
of vasopressors may be the strategy needed to reduce complica-
tion rates in free flap head and neck surgery. Further prospective
controlled studies focused on this topic are needed.
Conclusion
Perioperative i.v. fluid overload requiring postoperative ad-
ministration of furosemide was associated with higher risks
Fig. 4 Nomogram predicting
flap-related complications.
Abbreviations: Hb, hemoglobin;
mL, milliliters
Clin Oral Invest (2021) 25:5541–5550
5548
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of early surgical revision and flap-related complications in
head and neck free tissue transfer. In addition, excessive in-
traoperative fluid administration may result in an increased
number of flap-related complications. In contrast, the admin-
istration of vasopressors and inopressors per se seemed to
have no effect on early surgical revisions and flap-related
complications.
Acknowledgements We would like to thank Ayla Little for her efforts
and support in collecting and summarizing data. We thank Jeannie Wurz
for the linguistic editing of the manuscript and the correction of the formal
structure.
Funding Open Access funding provided by Universität Bern.
Declarations
Ethics approval Ethical approval of this study was provided by the
Ethical Committee of the Canton Bern, Switzerland (KEKBE 2019-
01824), on January 28, 2020, and the need for informed consent was
waived. It conforms with the STROBE (Strengthening the Reporting of
Observational Studies in Epidemiology) guidelines.
Conflict of interest The authors declare no competing interests.
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing, adap-
tation, distribution and reproduction in any medium or format, as long as
you give appropriate credit to the original author(s) and the source, pro-
vide a link to the Creative Commons licence, and indicate if changes were
made. The images or other third party material in this article are included
in the article's CreativeCommons licence, unless indicated otherwise in a
credit line to the material. If material is not included in the article's
Creative Commons licence and your intended use is not permitted by
statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.
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