We performed a prospective observational cohort study in a total of 60 patients who underwent head and neck cancer surgery with free-flap reconstruction in the head and neck surgery department from August 2015 through December 2017 at Ajou University Hospital and whose care followed the ERAS protocol. A total of 29 patients who underwent reconstructive surgery before July 2015 and whose care followed without the ERAS protocol were selected as non-ERAS group and compared to ERAS group. The non-ERAS group collected and analyzed data through a retrospective chart review.

Before implementation of the ERAS approach, perioperative care was directed by the individual surgeon and did not follow a specific protocol. Beginning in August 2015, a protocol was established according to the basic ERAS principles and applied to perioperative care. The main contents of the Ajou Hospital-developed ERAS protocol for head and neck cancer surgery with free-flap reconstruction patients were as follows. Patients were informed regarding the surgical procedure and precautions before surgery, and the operation proceeded with voluntary consent. Prophylactic intravenous antibiotics were administered 1 to 2 hours before surgery and preanesthetic medication was administered before anesthesia. Patients were routinely admitted to the intensive care unit (ICU) on the operation day, and ventilator weaning took place immediately if there were no cardiopulmonary difficulties. If there were no specific problems or complications on postoperative day (POD) 1, the patient was transferred to the general ward. Routine anticoagulation was performed with low-molecular weight heparin or alprostadil for 2 days through a central intravenous line. The urinary catheter and central intravenous line were removed on POD 1. Fluid replacement was managed in a goal-directed manner while avoiding excessive over- or underhydration. A standard polymeric enteral nutrition formula was administered starting on POD 1, and oral feeding training was started on POD 5 with sips of water while maintaining enteral nutrition. A cold liquid diet was started on POD 7, and enteral nutrition was discontinued when sufficient nutrition was satisfied by oral feeding. Immediately after the operation, analgesics were administered through the intravenous line to manage patient pain; paracetamol and available nonsteroidal anti-inflammatory drugs were used in combination. Opioid analgesics were also used at the physician's discretion. Analgesics were appropriately controlled during the hospitalization period according to the severity of patient's pain. A single postoperative antibiotic was administered through POD 7. Postoperative mobilization was enacted as soon as possible. Normally, the patient maintained a sitting position until wheelchair ambulation on POD 5, usually after maintaining absolute bedrest through POD 2. Patients began ward ambulation on POD 7. Flap monitoring was performed at 2-hour intervals for 2 days after surgery, and every 12 hours thereafter.

The medical information of patients who underwent head and neck cancer surgery with free-flap reconstruction was analyzed to determine an evaluation index. This study was approved by the Institutional Review Board of Ajou University Hospital (AJIRB-18-050). Patient demographics, including age, sex, comorbidities, and body mass index (BMI) were collected, and preoperative American Society of Anesthesiologists (ASA) physical status classification, were evaluated. The World Health Organization score and Karnofsky score (a form of performance score) were also assessed. In addition, each patient's head and neck cancer subsite, cancer staging (American Joint Committee on Cancer, 7th edition), total surgery duration and free-flap reconstructive surgery duration were collected.

Outcomes for the ERAS and non-ERAS groups were evaluated on the following factors. The ICU length of stay (LOS) and the hospital LOS were assessed. The starting times of adjuvant radiotherapy, oral feeding, and normal ambulation were measured. In addition, postoperative complications, such as surgical wound complications, pneumonia, delirium, and expiration, were analyzed.

Patients demographics are expressed as number and frequency (%), and continuous variables such as age, BMI, and outcome index are reported as means ± standard deviation. The chi-square test and Fisher extract test were used for comparison of categorical variables, while the Student's t-test was used for comparison of continuous variables. Multiple regression analysis was performed. Statistical significance was set at a P < 0.05. Data were collated and analyzed with IBM SPSS Statistics ver. 20.0 (IBM Co., Armonk, NY, USA).

Table 1 presents a comparison of patient characteristics between the ERAS and non-ERAS groups. Age, sex, preoperative status, and performance score were not significantly different between the 2 groups. Comorbidities, subsites of head and neck cancer, and cancer stage were also not significantly different. However, there was a significant difference in BMI between the ERAS group (23.09 ± 3.17) and the non-ERAS group (22.58 ± 3.32) (P = 0.036).

The mean length of ICU LOS was 1.20 ± 0.92 days for patients whose care followed the ERAS protocol, which was significantly lower than the 9.48 ± 7.13 days for the non-ERAS group (P < 0.0001) (Table 2). A significant difference in mean hospital LOS was also observed between the ERAS group (30.87 ± 20.73) and the non-ERAS group (59.66 ± 40.43) (P < 0.001) (Fig. 1). The starting times of adjuvant radiotherapy, oral feeding, and normal ambulation were significantly reduced in the ERAS group (P < 0.001). Complications related to surgery, including pneumonia, delirium, expiration, and surgical wound complications, were not correlated with application of the ERAS protocol (Table 2).

Multiple regression analysis was performed on all indexes, with hospital LOS as a dependent variable. The starting time of oral feeding (P < 0.001) and normal ambulation (P = 0.003) showed significant correlation with hospital LOS, and ICU LOS (P = 0.013) and preoperative ASA physical status classification (P = 0.018) were also significantly correlated with hospital LOS. The coefficient of determination (R2) of hospital LOS for these 4 indexes was 0.65, demonstrating reliability of about 65% (Table 3). On the other hand, total surgery duration and free-flap reconstructive surgery duration were not closely related to the extended hospital LOS.