10.14639/0392-100X-N2072
Objective. In this study, we aimed to describe the prospective implementation of the Enhanced Recovery after Surgery (ERAS) protocol in an Italian tertiary academic centre. Methods. Adult patients receiving surgery for primary or recurrent clinical stage III/IV squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx were enrolled. The primary objective was to evaluate the impact of the ERAS protocol on length of hospital stay (LOS). The secondary objective was to assess its impact on complications. To evaluate the results of the ERAS protocol, a matched-pair analysis was conducted, comparing ERAS patients with comparable cases treated before 2018. Results. Forty ERAS and 40 non-ERAS patients were analysed. There were no significant differences between the cohorts regarding age, gender, stage of disease, comorbidity, ASA score, and duration of surgery. A significantly shorter LOS for the ERAS group (median, 14 days; range, 10-19) than for non-ERAS patients (median, 17.5 days; range, 13-21) was observed (p = 0.0128). The incidence of complications was not significantly different (p = 0.140).Conclusions. Our study demonstrates that the introduction of an ERAS protocol in the daily practice is feasible, and can result in significant reduction in LOS.
text/xml
1827-675X
2072
en
Alberto Deganello
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
patient education handout
The Enhanced Recovery After Surgery (ERAS) protocol in head and neck cancer: a matched-pair analysis
Text.Serial.Journal
https://www.actaitalica.it/
42
Head and neck
2022-09-30
2022-03-17
2022-10-12
2022-10-12
325-333
1
Alberto Deganello
2022/09/30
10.14639/0392-100X-N2072
325
Unit of Otorhinolaryngology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; Unit of Otorhinolaryngology, Azienda Socio-sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy; * C. Piazza, P. Nicolai, A. Deganello share last authorship.
1827-675X
patient education handout
en
333
The Enhanced Recovery After Surgery (ERAS) protocol in head and neck cancer: a matched-pair analysis
https://www.actaitalica.it/article/download/2072/845
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:325-333; doi: 10.14639/0392-100X-N2072




Head and neck


The Enhanced Recovery After Surgery (ERAS)
protocol in head and neck cancer:
a matched-pair analysis
Protocollo di recupero ottimizzato (ERAS) in oncologia testa-collo:
un’analisi a coppie appaiate
Giacomo Bertazzoni1, Gabriele Testa2, Michele Tomasoni2, Davide Mattavelli2,3, Francesca Del Bon3, Nausica Montalto4,
Marco Ferrari4, Marco Andreoli5, Riccardo Morello1, Nicola Sbalzer6, Daniela Vecchiati6, Cesare Piazza2,3*, Piero Nicolai4*,
Alberto Deganello2,3*
1
  Department of Otorhinolaryngology, Azienda Socio-Sanitaria Territoriale di Cremona, Cremona, Italy; 2 Unit of Otorhinolaryngology,
Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; 3 Unit
of Otorhinolaryngology, Azienda Socio-sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy; 4 Section of Otorhinolaryngology-
Head and Neck Surgery, Department of Neurosciences, University of Padova, Azienda Ospedale Università Padua, Padua, Italy;
5
  Clinical Nutrition, Azienda Socio-Sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy; 6 Department of Anaesthesia and
Intensive Care, Azienda Socio-sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy
* C. Piazza, P. Nicolai, A. Deganello share last authorship.


SUMMARY
Objective. In this study, we aimed to describe the prospective implementation of the En-
hanced Recovery after Surgery (ERAS) protocol in an Italian tertiary academic centre.
Methods. Adult patients receiving surgery for primary or recurrent clinical stage III/IV
squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx were en-
rolled. The primary objective was to evaluate the impact of the ERAS protocol on length of
hospital stay (LOS). The secondary objective was to assess its impact on complications. To
evaluate the results of the ERAS protocol, a matched-pair analysis was conducted, compar-
                                                                                                  Received: March 22, 2022
ing ERAS patients with comparable cases treated before 2018.
                                                                                                  Accepted: July 7, 2022
Results. Forty ERAS and 40 non-ERAS patients were analysed. There were no signifi-
cant differences between the cohorts regarding age, gender, stage of disease, comorbidity,
                                                                                                  Correspondence
ASA score, and duration of surgery. A significantly shorter LOS for the ERAS group (me-
                                                                                                  Giacomo Bertazzoni
dian, 14 days; range, 10-19) than for non-ERAS patients (median, 17.5 days; range, 13-21)         Department of Otorhinolaryngology
was observed (p = 0.0128). The incidence of complications was not significantly different         Azienda Socio-Sanitaria Territoriale di Cremona,
(p = 0.140).                                                                                      viale Concordia 1, 26100 Cremona, Italy
Conclusions. Our study demonstrates that the introduction of an ERAS protocol in the              Tel. +39 0372 405282
daily practice is feasible, and can result in significant reduction in LOS.                       E-mail: giacomo.bertazzoni@asst-cremona.it
KEY WORDS: head and neck cancer, enhanced recovery after surgery, length of stay,
postoperative complications, patient education handout                                              How to cite this article: Bertazzoni G, Testa G,
                                                                                                    Tomasoni M, et al. The Enhanced Recovery Af-
                                                                                                    ter Surgery (ERAS) protocol in head and neck
RIASSUNTO                                                                                           cancer: a matched-pair analysis. Acta Otorhi-
Obiettivo. L’obiettivo dello studio è descrivere l’attuazione del protocollo di recupero po-        nolaryngol Ital 2022;42:325-333. https://doi.
stoperatorio ottimizzato ERAS in un centro ospedaliero universitario di terzo livello italiano.     org/10.14639/0392-100X-N2072
Metodi. Sono stati inclusi pazienti adulti operati per carcinoma squamoso di cavo orale,
orofaringe, laringe o ipofaringe stadi III/IV. L’obiettivo primario era valutare l’impatto del    © Società Italiana di Otorinolaringoiatria
protocollo sulla durata della degenza (LOS). L’obiettivo secondario era valutare l’impatto        e Chirurgia Cervico-Facciale
sulle complicanze. I risultati del protocollo ERAS sono stati analizzati con un confronto a
coppie appaiate, confrontando pazienti ERAS con casi paragonabili trattati prima del 2018.                       OPEN ACCESS
Risultati. Quaranta pazienti ERAS e 40 non-ERAS sono stati inclusi. Non sono state ri-            This is an open access article distributed in accordance with
scontrate differenze significative tra le due corti per quanto riguarda età, genere, stadio di    the CC-BY-NC-ND (Creative Commons Attribution-Non-
malattia, comorbilità, punteggio ASA e durata dell’intervento. La LOS era significativa-          Commercial-NoDerivatives 4.0 International) license. The
                                                                                                  article can be used by giving appropriate credit and mentio-
mente minore per il gruppo ERAS (mediana, 14 giorni; range, 10-19) rispetto ai pazienti           ning the license, but only for non-commercial purposes and
non-ERAS (mediana, 17,5 giorni; range, 13-21) (p = 0,0128). L’incidenza di complicanze            only in the original version. For further information: https://
non è risultata significativamente differente (p = 0,140).                                        creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                          325
G. Bertazzoni et al.




Conclusioni. Lo studio ha dimostrato che l’introduzione di un protocollo ERAS nella pratica clinica è fattibile e può portare ad una riduzione
della LOS.
PAROLE CHIAVE: tumori testa-collo, recupero ottimizzato dopo chirurgia, lunghezza della degenza, complicanze postoperatorie, opuscoli
informativi per pazienti



Introduction                                                             discharge). The secondary objective was to assess its im-
                                                                         pact on the incidence of complications.
The Enhanced Recovery After Surgery (ERAS) protocol is
an evidence-based, multimodal, multidisciplinary, and inte-
                                                                         ERAS protocol
grated program of interventions aimed at minimising meta-
                                                                         The protocol was designed according to previously pub-
bolic stress and postoperative organ dysfunction, reducing
                                                                         lished recommendations from the ERAS society and tak-
complications, and shortening the duration of hospitalisation.
                                                                         ing into account previous protocols implemented for HN
Recent experiences since 2017 have confirmed that the im-
                                                                         surgery 2,11. A multidisciplinary team composed of otolar-
provements associated with ERAS in other specialties can be
                                                                         yngologists, nurses, speech therapists, and anaesthesiolo-
transferred to the head and neck (HN) scenario 1-5. In addition,
                                                                         gists collaborated on the elaboration of internal procedures
a consensus review and recommendations for patients under-
                                                                         and guidelines to implement the protocol. Furthermore, the
going HN surgery with free flap reconstruction have been
                                                                         team drafted an informative booklet to promote pre-ad-
published 6. However, in this field, the evidence is still limited
                                                                         mission education of patients, describing in appropriate
compared to other specialties, and highly prevalent issues in
                                                                         and comprehensible language what patients should do to
HN cancer patients, such as preoperative malnutrition, should
                                                                         promote their health before and after surgery (e.g., appro-
be more intensively addressed using ERAS protocols.
                                                                         priate nutrition, cessation of smoking/alcohol), as well as
In this study, we aimed to describe the prospective imple-
                                                                         detailing the postoperative course to promote patient en-
mentation of the ERAS protocol in an Italian tertiary aca-
                                                                         gagement in early mobilisation, respiratory exercises, pain
demic centre. To precisely evaluate its impact, a matched-
                                                                         assessment/control, and tracheostomy management.
pair analysis between the ERAS series and patients treated
                                                                         Preoperative nutritional/metabolic status was assessed by
before implementation of the protocol was performed.
                                                                         calculating the body mass index (BMI) and Nutritional Risk
                                                                         Assessment Score (NRS2002). Whenever the NRS2002
Materials and methods                                                    was ≥ 3, medical nutritional evaluation was performed by a
This prospective study was conducted from August 2018 to                 dedicated specialist. The decision to place a percutaneous
September 2019 in the Department of Otorhinolaryngolo-                   endoscopic gastrostomy (PEG) or a radiologically insert-
gy - Head and Neck Surgery of the University of Brescia,                 ed gastrostomy (RIG) pre- or postoperatively was taken by
Italy.                                                                   considering the potential advantage to the patient following
                                                                         a previously published model 7.
Patient selection                                                        Immunonutrition (Impact® Oral, Société des Produits
Patients older than 18 years receiving HN surgery for pri-               Nestlé S.A., Vevey, Switzerland) was prescribed to all
mary or recurrent clinical Stage III/IV squamous cell car-               patients: 3 servings per day for 7 days before surgery if
cinoma (SCC) of the oral cavity, oropharynx, larynx, or                  malnourished according to the nutritional evaluation, for 5
hypopharynx were enrolled.                                               days if not.
Exclusion criteria were: a) active psychiatric disease, in-              As per normal clinical practice, patients with diabetes were
cluding substance and/or alcohol abuse; b) Karnofsky per-                hospitalised the day before surgery and treated with a con-
formance status < 70; c) uncontrolled/acute comorbidities,               tinuous insulin infusion to control glycaemia.
such as recent acute cardiac ischaemic attack, or severe pul-            In preparation for surgery, patients consumed a carbo-
monary, hepatic, renal, or cardiac organ failure; d) Comor-              hydrate-rich drink (Nutricia Fantomalt, Danone, Paris,
bidity-Polypharmacy Score (CPS) > 22; e) language barrier.               France), which consisted of 800 ml the evening before sur-
                                                                         gery and 400 ml 2-3 hours before surgery.
Study objectives                                                         The risk of deep vein thrombosis was calculated using the
The primary objective was to evaluate the impact of the                  Caprini Score 8; prophylactic antithrombotic therapy was
ERAS protocol on both hospitalisation and dischargeabil-                 administered accordingly.
ity (defined as the absence of active medical or surgical                The intra- and postoperative procedures of the protocol are
problems requiring hospitalisation and preventing actual                 listed in Table I.



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                                                                                                              ERAS in head and neck cancer: a matched-pair analysis




Postoperative free flap monitoring was performed at 12                                 ables were analysed with Student’s t test, Welch’s t test, and
hours after the end of surgery, in accordance with current                             Mann-Whitney U test. Student’s t test was used for paired
evidence, which shows that more frequent monitoring does                               samples or Wilcoxon test according to data pairing, nor-
not change the rate of flap salvage 9.                                                 mality or non-normality, and homoscedasticity or non-ho-
                                                                                       moscedasticity of distributions.
Sample size                                                                            In order to evaluate the results of implementation of the
Study numerosity was calculated for the matched paired                                 ERAS protocol, a matched-pair analysis was conducted.
analysis between ERAS and non-ERAS patients, taking as                                 For each patient who participated in the study, a com-
primary endpoint the length of hospital stay (LOS). Da-                                parable case among patients treated before 2018 (2000-
ta extrapolated from the literature indicated 14.55 days                               2017) was identified. In order to minimise the risk of
of hospitalisation for ERAS patients vs 18 days for non-                               bias, patients were matched based on cancer stage and
ERAS patients, with a standard deviation of 7.48 days 6.                               extent of surgery (Tab. II). Other factors potentially in-
For an inferiority test, assuming that the difference between                          fluencing the LOS, which were identified through a liter-
the two groups is at least 4 days, considering a significance                          ature review 5,10-21 and are reported in Table II, were also
level of 0.05 and planning a one-tailed comparison using                               considered in the matched-pair analysis. Type of sur-
Student’s t test (or non-parametric equivalent), an adequate                           gery, reconstruction, neck dissection, overall comorbidi-
study power (77%) was deemed to require 40 cases for                                   ties assessed through Comorbidity-Polypharmacy Score
each group.                                                                            (CPS), American Society of Anesthesiologists (ASA)
                                                                                       status and preoperative staging were given priority in the
Statistical analysis                                                                   selection of patients to be matched.
Descriptive statistics (Shapiro-Wilk normality test, mean,                             Whenever an exact match between two patients was
standard deviation, median, and interquartile range) were                              not possible, an overall balance between the two groups
calculated, as appropriate, for each group. Qualitative vari-                          (ERAS and non-ERAS) was sought, including an equal

Table I. Intra- and postoperative procedures of the protocol.
 Intraoperative
 Antibiotic prophylaxis prior to incision, according to the current recommendations of the Italian Association of Head and Neck Oncology (AIOCC)
 Anesthesiologic premedication for anxiolysis if needed
 Standard anesthesiologic protocol
 Prevention of hypothermia with fluid warmers and forced air patient warming devices
 Fluid balance and, if necessary, goal directed fluid therapy
 Total intravenous anaesthesia (TIVA) using entropy monitoring
 Slow magnesium sulphate and lidocaine infusion prior to surgical incision, followed by continuous perfusion of lidocaine
 Anti-emetic prophylaxis for postoperative nausea and vomiting (PONV)
 Multimodal pain management following opioid-sparing strategies
 Postoperative
 Intensive care unit (ICU) admission if necessary (free flap, frail patient); transfer to the general surgical ward as soon as the patient is stable.
 Urinary catheter removal within 24 hours after surgery
 Nutrition
 Start of enteral nutrition through nasogastric or PEG tube at 12-24 hours after the end of surgery
 Immunonutrition, 2 servings per day for 10 days
 Tracheostomy management
 Tracheostomy tube cuff deflation on postoperative day 1
 Assessment of tolerance to tracheotomy closure using a capped small-caliber cannula from postoperative day 3
 Tracheostomy tube removal and compressive medication of the stoma after keeping the cannula closed for 24 hours
 Suture of tracheostomy under local anaesthesia at 24 hours after uneventful tracheostomy tube removal
 Assisted mobilisation within 24 hours from surgery, whenever possible; implementation of a daily and incremental mobilisation program over the following days
 Wound dressing changes as needed, following daily assessment
 Speech and language therapist evaluation on postoperative day 1




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G. Bertazzoni et al.




Table II. Matched pair analysis: items and groups.
                                                                                     Number of patients               Percentage of     P-value    Rate of
                                                                                                                        patients                  Symmetry
                                                                              ERAS                  NON-ERAS       ERAS      NON-ERAS
    Type of surgery on T                                                                                                                0.912*      95%°
                                                                      Resection of the oral               24         24         60        60
                                                                     cavity and oropharynx
                                                                       with tracheotomy
                                                                     Pharyngolaryngectomy                 4          3          10        7.5
                                                                         Laryngectomy                     12         13         30       32.5
    Neck dissection                                                                                                                     0.230*      80%°
                                                                            Bilateral                     20         17         50       42.5
                                                                          Monolateral                     19         18        47.5       45
                                                                         Not performed                     1          5         2.5      12.5
    Clinical stage of disease1,2,7                                                                                                      0.102*      75%°
                                                                             Stage 1                      2          0          5          0
                                                                             Stage 2                      0          4          0         10
                                                                             Stage 3                      8          9          20       22.5
                                                                             Stage 4                      30         27         75       67.5
    Comorbidity polypharmacy score                                                                                                      0.758*      85%°
                                                                              Mild                        26         29         65       72.5
                                                                            Moderate                      13         10        32.5       25
                                                                             Severe                        1          1         2.5       2.5
    ASA Score 8,9                                                                                                                       1.000*      100%
                                                                            Class 1-2                     19         19        47.5      47.5
                                                                            Class 3-4                     20         20        52.5      52.5
    Chronic obstructive pulmonary disease 10,11                                 6                          7         15        17.5     0.761*       86%
    Diabetes mellitus 10-12                                                     5                          3        12.5        7.5     0.456*      60%°
    Liver disease 11                                                            3                          3         7.5        7.5     1.000*      100%
    Weight loss (BMI < 19 or loss > 10%) 13                                    12                          9         30        22.5     0.445*      75%°
    Preoperative haemoglobin < 11 g/dL 14                                       2                          5          5        12.5     0.235*       40%
    Preoperative radiation therapy greater than 60 Gy 15                        3                          4         7.5        10      0.692*       75%
    Active smoker status 14                                                    14                         14         35         35      1.000*      100%
    Sex (male)                                                                 26                         28         65         70      0.633*       93%
                                                                                                                    ERAS     NON-ERAS
    Mean age 10                                                          64.4 ± 15.03             62.8 ± 13.76     0.214**    0.214**
    Operative time 8,16,17                                               471.1 ± 142.2           459.92 ± 139.03   0.486**    0.486**
*
    Chi-square test; ** Paired t-test; ° symmetry rate favours the NON-ERAS group.


number of patients presenting the same characteristics in                                     2017), in order to make sure that study results were not af-
the two groups (e.g., active smoker status or ASA score). If                                  fected by changes in medical practice over time, LOS was
an equal distribution of patients with similar features could                                 also compared with all patients who would have met the
not be obtained, whenever possible, a greater number of                                       study inclusion criteria but who were treated in our centre
patients with favourable features that potentially play a                                     during 2017 (before ERAS implementation).
beneficial effect on postoperative outcomes was tolerated
in the non-ERAS group (e.g., fewer patients with weight                                       Results
loss were included in the non-ERAS group).                                                    Protocol implementation and compliance
In addition, since the pair-matched group encompassed pa-                                     Compliance data are shown in Table III. Overall, protocol ad-
tients who had been treated over a long time interval (2000-                                  herence ranged from 70 to 100% in most items. In particular, a



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                                                                                                       ERAS in head and neck cancer: a matched-pair analysis




high rate of protocol adherence was observed for preoperative                     Matched-pair analysis
patient education, nutrition, immunonutrition, preparation for                    A total of 80 cases were analysed, 40 ERAS and 40 non-
surgery, and overall postoperative management (removal of                         ERAS patients. Patient features that were considered in the
urinary catheter, early start of enteral and oral feeding, early                  matched pairing of the two cohorts are summarised in Ta-
mobilisation, management of the tracheotomy cannula).                             ble II. There were no significant differences between the


Table III. Adherence to the protocol.
                                                                                                                         Patients         Percentage
 Preoperative education
 Intervention for smoking cessation                                                                                        14/14             100%
 Patients who received preoperative counselling and information booklet                                                    40/40             100%
 Preoperative risk assessment
 Patients with NRS-2002 ≥ 3 who underwent nutritional evaluation                                                           17/21              81%
 Planned preoperative/intraoperative PEG placement according to Wake Forest School of Medicine formula or medical          13/40             32.5%
 indication
 Patient with positive Caprini score who were administered correct prophylactic anticoagulant therapy                      19/19             100%
 Anaesthesia
 Total intravenous anaesthesia (TIVA) using entropy monitoring                                                             37/40             92.5%
 Opioid sparing analgesia with slow magnesium sulphate and lidocaine infusion prior to surgical incision and               39/40             97.5%
 continuous perfusion of lidocaine
 Antibiotic prophylaxis prior to incision                                                                                  40/40             100%
 PONV prophylaxis                                                                                                          32/40             80%
 Nutrition and immunonutrition
 Preoperative carbohydrate-rich drink                                                                                      40/40             100%
 Immunonutrition
   Preoperative                                                                                                           39/40              97.5%
      Complete                                                                                                              33/40              82.5%
      Partial                                                                                                                6/40              15%
   Postoperative                                                                                                          37/40                92.5%
 Postoperative course
 Number of days spent in ICU; median (IQR)                                                                                1 (1-1)
 Removal of urinary catheter within 24 hours after the end of surgery                                                     33/40              82.5%
 Start of mobilisation
    Assisted within 24 hours after the end of surgery                                                                     39/40              97.5%
    Autonomous (median postoperative day of start on 39 patients)                                                         3 (2-6)
 Nutrition
    Enteral
       Within 12 hours after the end of surgery                                                                             8/40              20%
       Within 24 hours after the end of surgery                                                                            31/40             77.5%
    Number of postoperative days before oral feeding (median, 37 patients)                                               9 (7-12.5)
 Tracheostomy management
    Tracheostomy tube cuff deflation on postoperative day 1                                                               39/40              97.5%
    26 patients underwent temporary tracheostomy:
       Assessment of tolerance to tracheostomy closure using a capped small-calibre cannula from postoperative day 3      26/26              100%
       Tracheostomy tube removal and compressive medication of the stoma after keeping the cannula closed for 24          26/26              100%
       hours consecutively
       Suturing of tracheostomy under local anaesthesia 24 hours after uneventful tracheostomy tube removal                6/26               23%
 Speech, swallowing and language therapist evaluation on postoperative day 1                                              21/39               54%




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G. Bertazzoni et al.




cohorts regarding age, gender, stage of disease, CPS score,    Complications
ASA score, rate of diabetes mellitus, chronic liver disease,   The impact of ERAS on complications is shown in Ta-
preoperative weight loss, active smoker status and mean        ble IV. In the ERAS group, 20 complications in 16 patients
duration of surgery.                                           (40%) were recorded, while in the control group there were
                                                               32 complications among 20 patients (50%). The difference
Postoperative length of stay                                   was not statistically significant (p = 0.140).
The dischargeability was significantly shorter (p = 0.0117)
in the ERAS group (median, 12 days; range, 9-17) than          Discussion
in the non-ERAS group (median, 16 days; range, 13-20).         The results of the present study indicate that implementation
The same was observed for postoperative hospitalisation        of the ERAS protocol in HN surgery has significant impact in
(p = 0.0128), with shorter LOS (median, 14 days; range,        reducing the LOS, and confirm what was observed in similar
10-19) for the ERAS group than for non-ERAS patients           studies1,4,5. The absence of a significant difference between
(median, 17.5 days; range, 13-21).                             median LOS in the non-ERAS group and the 2017 cohort
                                                               confirms that the former can be reasonably considered a re-
Comparison with the 2017 cohort                                liable control group, without major selection bias impacting
Ninety-one patients treated in 2017 would have met in-         LOS. Our results are also corroborated by the high level of
clusion criteria for the present study, and therefore their    correspondence between the two matched-paired groups. The
postoperative LOS was compared with the ERAS and non-          process used to select control cases in the non-ERAS group
                                                               is probably the most complex attempted to date among HN
ERAS groups. No significant difference in LOS was ob-
                                                               ERAS studies with the intent of minimising potential selec-
served between the non-ERAS group (median, 17.5 days;
                                                               tion biases 4. Undoubtedly, since an ideal match is not always
range, 13-21) and the 2017 cohort (median, 17 days; range,     possible, some factors included in the pairing were hierarchi-
13-23) (p = 0.9712), while a significantly shorter LOS was     cally considered, in accordance with the previous literature.
seen in the ERAS group (median, 14 days; range, 10-19)         In particular, preoperative staging, type of surgery and recon-
compared to the 2017 cohort (median, 17 days; range, 13-       struction, CPS and ASA scores were considered first in the
23), with a median gain of 3 days (p = 0.0131).                selection of patients to be matched. When it was not possible


Table IV. Incidence and type of complications.
                                                                 Number of patients               Percentage of patients
                                                               ERAS           NON-ERAS           ERAS            NON-ERAS
 Incidence of complications
 Total complications                                            16                20              40                 50
    Medical complications only                                   8                11              20                27.5
    Surgical complications only                                  6                 6              15                 15
    Medical and surgical complications                           2                 3               5                7.5
    More than 24 hours after surgery                            12                14              30                 35
    Within 24 hours after surgery                                3                 3              7.5               7.5
    Both within and after 24 hours of surgery                    1                 3              2.5               7.5
 Patients who had no complications                              24                20              60                 50
 Type of complication and its incidence
 Bleeding                                                       2                  3               5                 7.5
 Surgical site infection                                        2                  2               5                  5
 Wound dehiscence                                               0                  3               0                 7.5
 Salivary fistula                                               4                  1              10                 2.5
 Flap failure                                                   1                  2              2.5                 5
 Deep vein thrombosis                                           1                  0              2.5                 0
 Pneumonia                                                      2                  3               5                 7.5
 Other                                                          8                 13              20                37.5




330
                                                                                                    ERAS in head and neck cancer: a matched-pair analysis




to obtain a match for all factors identified for comparison, a                     tracheostomy still in place 2, while in all EU studies, as well
balance between the two samples was sought by selecting and                        as in the present one, patients were discharged after regain-
including in the non-ERAS group an equal global number of                          ing oral feeding and tracheostomy closure 2,5.
the same characteristics, forgoing equality between individual                     Early mobilisation and feeding are considered among the
pairs. Furthermore, if this balance could not be achieved, an                      major determinants of the rapid recovery observed in the
excess of favourable factors was tolerated for non-ERAS pa-                        ERAS cohort 1,2. The median postoperative day (POD) of
tients. Accordingly, a greater prevalence of factors associated                    initiation of oral feeding for our ERAS patients was POD
with longer LOS was observed among ERAS patients (3 more                           9 (range, POD 7-12.5), while in the study by Bater et al. it
patients with BMI < 19 or weight loss > 10%, 2 more patients                       was POD 8 2. This could partially explain the shorter medi-
with diabetes mellitus, and 3 more patients with moderate                          an hospital stay of patients in the UK study compared with
rather than mild CPS), further enhancing our results.                              ours, and the greater difference in terms of LOS between
Significant reduction in mean postoperative LOS was                                control and experimental samples in the two studies (4 days
demonstrated in the majority of studies on ERAS in HN                              for the Bater study 2 vs 3.5 in ours). Indeed, further early
cancer surgery published to date (Tab. V). Of note, LOS                            initiation of oral feeding could result in greater reduction
reduction was not the primary endpoint in all investiga-                           in LOS without leading to an increased incidence of com-
tions 22,23, and preoperative patient education was not per-                       plications 2.
formed in some 22,23. These discrepancies could explain                            LOS is a general indicator of the quality of care, since pro-
why a significant difference in LOS between ERAS and                               longed hospitalisation determines not only an increase in
non-ERAS patients was not always demonstrated. Notice-                             overall costs, but also a significant increase in the incidence
ably, one of the two studies that did not demonstrate LOS                          of in-hospital/perioperative complications, especially in-
reduction showed significant improvements in LOS in the                            fections and mortality 24. However, LOS does not represent
intensive care unit (ICU) and costs 22.                                            the only parameter to assess the impact of ERAS imple-
Another relevant aspect to consider is the difficulty in                           mentation: economic factors such as better allocation of re-
drawing substantial comparisons between studies con-                               sources, or reduction of length of ICU occupation, should
ducted in different healthcare systems with heterogeneous                          also be taken into account. However, an economic analysis
organisation, imbalanced availability of social services,                          of savings related to LOS reduction in ERAS patients was
different post-hospital care facilities and variability in the                     not performed in the present study.
overall efficiency of public or insurance-based services. In-                      As mentioned, one of the problems in employing LOS as
terestingly, studies on ERAS in HN surgery in the United                           the main outcome measure is that this parameter is affected
States (US) reported a LOS of < 10 days both before and                            by other variables that are not addressed by the ERAS pro-
after ERAS implementation 4,22, in contrast to European                            tocol, leading to difficulties in interpretation of the results.
(EU) studies that have a longer average LOS 5,15 (Tab. V).                         In an attempt to univocally identify the results of ERAS
The analysis of the possible causes of such differences be-                        on the patients’ clinical course, the dischargeability, in the
tween EU and US centres is beyond the scope of the current                         absence of active medical or surgical problems requiring
study, although it is possible that insurance-based systems                        hospitalisation and actual discharge were distinguished.
have historically put greater emphasis on the development                          Significant discharge delay can prolong LOS and during
of strategies to shorten LOS, even before implementation                           this time the patient, although medically and surgically a
of ERAS 22. In particular, US studies mention that patients                        candidate for discharge (i.e. dischargeable), remains hospi-
were discharged with nasogastric feeding tube 4,22 or with                         talised for reasons that are not related to clinical conditions.


Table V. Impact of ERAS protocols for oncological surgery of the head and neck on length of stay.
 Study                                                               Number of patients                  Length of stay (days)
    Name                                                  Study type        ERAS    Control group       ERAS          Control group        P-value
    Current study                                         Prospective        40      40 (matched)    14 (10-19.5)
                                                                                                                *
                                                                                                                      17.50 (13-21)*
                                                                                                                                            0.013
    Bater 2017 2                                          Prospective       100           40          10 (8-14)*      14.00 (11-21)*        0.003
    Jandali 2019 4                                       Retrospective      92            93          7.8 ± 4.8**      9.7 ± 4.7**          0.008
    Coyle 2016 5                                          Prospective        31            -        14.55 ± 7.48**         18**               -
    Bertelsen 2020 22                                     Prospective        61           61              10               8.5              0.346
    Kiong 2021 1                                         Retrospective      200     200 (matched)     7.2 ± 2.3**      8.7 ± 4.2**         < 0.001
*
    median (first quartile-third quartile); ** mean ± standard deviation.




                                                                                                                                                     331
G. Bertazzoni et al.




A review on the subject identified insurance issues, need for    Nevertheless, rates of compliance to the protocol were high
transfer to another facility, undergoing surgery on the last     overall, and compare favourably with those reported by
days of the week, and eligibility for patient discharge early    Coyle and Jandali 4,5. The assessment of compliance with
or late in the week as significant determinants of discharge     the protocol is a fundamental aspect of the ERAS philoso-
delay. In our study, discharge was postponed mainly due to       phy and it is surprising that, so far, it has been analysed by
delays in the organisation of home care, unavailability of       so few studies in the HN literature 4,5. Reporting compli-
social services if patients were discharged over the week-       ance data is fundamental in the presentation of the ERAS
end, procrastination of medical consultations from other         results, since it allows to fully understand and interpret the
specialists, and, above all, the long time needed to deliver     results. As a consequence, all studies reporting no differ-
health care supplies to the patient’s home. The difference       ences in outcome measures after ERAS implementation do
between median LOS until discharge and dischargeability          not mention data on protocol adherence. In addition, ad-
was 2 days in the ERAS group, while dischargeability was         dressing areas of low compliance may give the opportu-
not evaluated in the 2017 cohort.                                nity to further improve patient outcomes, thus broadening
While dischargeable ERAS patients spent on average 2 ex-         the scope and opportunities offered by adopting the ERAS
tra days in the hospital before actual discharge, non-ERAS       framework.
patients spent an average of 1.5 days. A possible reason for
this difference is that the collection of data for the control   Conclusions
sample was performed retrospectively, and estimation of
dischargeability was not always straightforward. It is rel-      Our study demonstrated that the introduction of an ERAS
evant to note that optimised management of organisation-         protocol in the daily practice is feasible, as shown by the ex-
al aspects could significantly affect LOS in our healthcare      cellent adherence to the protocol, and can result in significant
system, with potential reductions that are similar to what       reduction in LOS. As with all ERAS protocols, due to the
can be attributed to the ERAS implementation itself.             multimodal nature of the program, assessing the impact of
The ERAS protocol was also associated with a positive            each individual procedure implemented is not possible. The
trend in reduction of postoperative complications that was       study also gave us the opportunity to update our practice and
not statistically significant. This aspect is most likely re-    deliver up-to-date care, and can be a starting point for further
lated to the relatively low number of cases included, since      discussion to address failures and improve outcomes.
the sample was not sufficiently powered considering this
outcome measure. Secondly, it is likely that complications       Acknowledgements
were more attentively reported in the prospective ERAS           We are grateful to the nursing and speech therapy staff of
group, while being underestimated in the retrospective           the Azienda Socio-Sanitaria Territoriale Spedali Civili di
control group. Of note, a shorter LOS in the ERAS group,         Brescia who took part in the study with enthusiasm, giving
despite a comparable rate of complications, could indicate       insightful feedback. In particular, we would like to thank
quicker recovery of patients, which could be attributed to       head nurse Simona Rossi, nurses Wilma Salini, Emanuela
the ERAS protocol. In the literature, few studies have thor-     Defendi, Rossella Rizzi and Noemi Consoli and speech
oughly analysed the complication rate 1,3,22 and in some HN      therapist Claudia Salone for their leadership and outstand-
cancer ERAS protocols this aspect has not been satisfacto-       ing contribution to protocol implementation and their work
rily evaluated 4. On the other hand, a recent retrospective      in drafting informative booklets for patients.
pair-matched study, which included 200 pairs of patients,
showed a significant reduction in both LOS and medical           Conflict of interest statement
complications 1.                                                 The authors declare no conflict of interest.
The implementation of the ERAS protocol was challenging
due to organisational difficulties. For example, patient re-     Funding
cruitment was operator-dependent and the crucial step was        This research did not receive any specific grant from fund-
to propose and illustrate the ERAS protocol to all potential-    ing agencies in the public, commercial, or not-for-profit
ly eligible patients at first contact in order to immediately    sectors.
implement the preoperative education and risk assessment
representing the first gate entry for inclusion in the pro-      Author contributions
spective cohort. Many patients were non-eligible because         GB designed the study, supervised and participated in data
the preoperative part of the protocol could not be imple-        collection and analysis, wrote the main article draft. GT
mented.                                                          collaborated to data collection and analysis and to initial



332
                                                                                                      ERAS in head and neck cancer: a matched-pair analysis




manuscript drafting. MT collaborated to study design and                             sis in otolaryngology-head and neck surgery: state of the art re-
                                                                                     view. Otolaryngol Head Neck Surg 2018;158:627-636. https://doi.
manuscript drafting. DM supervised study design, data col-                           org/10.1177/0194599818756599
lection and analysis and contributed to manuscript draft-                       9
                                                                                     Patel UA, Hernandez D, Shnayder Y, et al. Free flap reconstruction
ing. FDB supervised study design and contributed to manu-                            monitoring techniques and frequency in the era of restricted resident
script drafting. NM contributed to study design and data                             work hours. JAMA Otolaryngol Head Neck Surg 2017;143:803-809.
collection. MF contributed to study design and statistical                           https://doi.org/10.1001/jamaoto.2017.0304
                                                                                10
                                                                                     McDevitt J, Cancela Mde C, Kelly M, et al. Tracheostomy and infec-
analysis. MA, RM, NS and DV contributed to data col-                                 tion prolong length of stay in hospital after surgery for head and neck
lection and study design. CP, PN and AD supervised the                               cancer: a population based study. Oral Surg Oral Med Oral Pathol Oral
overall work, guided the study design process and the bib-                           Radiol 2016;121:22-28. https://doi.org/10.1016/j.oooo.2015.08.004
liographic research, and contributed to the final version of                    11
                                                                                     Genther DJ, Gourin CG. Effect of comorbidity on short-term out-
                                                                                     comes and cost of care after head and neck cancer surgery in the elder-
the manuscript.                                                                      ly. Head Neck 2015;37:685-693. https://doi.org/10.1002/hed.23651
All authors contributed to manuscript drafting and ap-                          12
                                                                                     Goepfert RP, Hutcheson KA, Lewin JS, et al. Complications, hospi-
proved the final version.                                                            tal length of stay, and readmission after total laryngectomy. Cancer
                                                                                     2017;123:1760-1767. https://doi.org/10.1002/cncr.30483
Ethical consideration                                                           13
                                                                                     Sweeny L, Rosenthal EL, Light T, et al. Outcomes and cost impli-
This prospective study was conducted according to the eth-                           cations of microvascular reconstructions of the head and neck. Head
                                                                                     Neck 2019;41:930-939. https://doi.org/10.1002/hed.25424
ical standards established in the 1964 Declaration of Hel-                      14
                                                                                     Choi JE, Kim H, Choi SY, et al. Clinical outcomes of a 14-day in-hos-
sinki (revised in 2013), and approved by the local Ethics                            pital stay program in patients undergoing head and neck cancer sur-
Committee (“Comitato Etico di Brescia”, Protocol Number                              gery with free flap reconstruction under the National Health Insur-
3131).                                                                               ance System. Clin Exp Otorhinolaryngol 2019;12:308-316. https://
                                                                                     doi.org/10.21053/ceo.2018.01235
Written informed consent was obtained from each partici-                        15
                                                                                     Girod A, Brancati A, Mosseri V, et al. Study of the length of hospi-
pant/patient for study participation and data publication.                           tal stay for free flap reconstruction of oral and pharyngeal cancer in
                                                                                     the context of the new French casemix-based funding. Oral Oncol
                                                                                     2010;46:190-194. https://doi.org/10.1016/j.oraloncology.2009.12.002
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