Postoperative Opioid Use and Ileus Occurrence---A Case Control Study

Postoperative ileus (POI) is a significant complication after colorectal surgery, with reported incidence ranging from 10\~30%, leading to increased morbidity, hospital length of stay, and thus medical cost. To determine the risk factors for POI is one of the key elements for Enhanced Recovery after Surgery protocol. Increased perioperative opioid usage has been proposed as an independent risk factor for postoperative ileus, as perioperative opioid minimization has proposed to be an effective measure to decrease the incidence of POI. Although opioids are widely used to attenuate stress during surgery, and represent the cornerstone of pain treatment, anesthesiologists are strive to minimize opioid use to decrease opioid-related GI side effects. In this study, the investigators aim to find out the general occurrence of POI in the laparoscopic colorectal surgery and the effects of the postoperative opioid usage on this outcome. The strategies of opioid minimization was also investigated.

2.1 Study design For this case-control study, all elective laparoscopic colorectal procedures performed at a university hospital between Jan 2018 and June 2020 were retrospectively collected by reviewing the institutional colorectal surgery database. The study protocol was approved by the Institutional Review Board of Peking University People's Hospital (2021PHB144-001, May 24, 2021), Beijing, China, and informed consent was waived due to the retrospective design.

The anesthesia medical information system was searched for patients aged 18 years old and above, undergoing elective laparoscopic colorectal procedures who received patient controlled intravenous analgesia postoperatively. Patients were excluded if they had chronic opioid use, converted to open, admitted to intensive care unit(ICU), patient controlled analgesia (PCA) regimens other than sufentanil, PCA used shorter than 48 hours, or incomplete postoperative opioid usage record. Patients were followed up until discharge from the hospital.

2.2 Patient allocation Patients who experienced postoperative ileus were included in ileus group. In accordance with the definition of Vather et al, diagnosis of postoperative ileus required 2 or more of following persistent symptoms on the fourth postoperative day and onward: nausea and vomiting, inability to tolerate solid or semi-liquid diet or failure to pass gas or stool during a 24 hour period, abdominal distension and radiological evidence of ileus. Patient charts, including radiographs were evaluated retrospectively. Diagnosis of an ileus was confirmed clinically and radiographically in all cases. The control group (at a 1:1 ratio) was matched by selecting the same range of age (±5 years of age), the same grade of American Society of Anesthesiology(ASA) classification, and the same types of surgery (colectomy, rectectomy, whole colon resection, or others).

2.3 Perioperative management All patients received standard anesthesia protocol for laparoscopic colorectal procedures within Peking University People's Hospital. Patients might received bilateral transversus abdominis plane(TAP) blocks (0.3% Ropivacaine of 30\~40ml under the ultrasound guidance) at the discretion of the anesthesiologist in charge.

General anesthesia was induced using etomidate (0.2-0.6 mg/kg) and sufentanil (0.3 μg/kg) and maintained with continuous infusion of propofol (4-6 mg/kg/h) to target a bispectral index of 40-60. Cisatracurium (0.15 mg/kg) was injected intravenously to facilitate endotracheal intubation. Intravenous sufentanil (0.1 μg/kg) was added before skin incision. During surgery, continuous infusion of remifentanil (0.1-0.2 μg /kg/min) was adjusted to keep heart rate (HR) and mean arterial blood pressure (MAP) within 80-120% of baseline. Hypotension (MAP \< 80% of baseline) lasting for 3 min was managed with a bolus of 6 mg of ephedrine or 50 μg of phenylephrine. Bradycardia (HR \< 45/min) was treated with atropine (0.25-0.5 mg). At the end of surgery, neostigmine (1 mg) and atropine (0.5 mg) were used to antagonize neuromuscular blockade, and tracheal extubation was performed when the patient was fully awake and breathing adequately. Patients were transferred to the post-anesthesia care unit (PACU) and discharged when the Modified Aldrete Score reached 10.

2.4 Postoperative pain management Postoperative pain management was charged by the acute pain service(APS). Acute pain or side effects related to the opioid was managed through the setting of intravenous patient-controlled analgesia(PCA) device. Patients received intravenous, intramuscular or oral analgesic rescue only after the PCA withdrawal.

In general, a patient-controlled analgesia (PCA) device was attached after tracheal extubation. The PCA was set to provide a bolus of 2\~3μg sufentanil (1 μg/ml) with a lockout time of 10\~15 min with or without basal infusion, 2\~3ml/h (sufentanil 1μg/ml), which was set at the discretion of the anesthesiologist in charge according to the patient's age and weight. After surgery, pain score was verbally rated using the 11-point numeric rating scale (NRS), on which 0 indicates no pain and 10 indicates worst imaginable pain. Patients could self-administer intravenous sufentanil bolus via PCA (2\~3μg, 1 μg/ml) postoperatively as rescue analgesia when the NRS score was ≥4, or as needed. PCA was maintained for at least the first 48 h after surgery.

2.5 Study outcomes and measurements Multiple potential risk factors for POI were considered based on literature review. Baseline factors included age(matched), gender, BMI, presence of major comorbidities (cardiovascular diseases, cerebral diseases, pulmonary diseases, or diabetes), ASA classification (matched), and previous abdominal surgery. Operative factors included type of surgery(matched), length of the surgery, estimated blood loss, total input, time to pass stool in patients' without enterostomy, time to tolerance of oral diet, and postoperative length of hospital stay. Analgesia related risk factors included TAP block, intra-operative opioid use(converted into equivalent doses of morphine, mg/kg), postoperative day 1 (POD1) and total post-operative opioid (Sufentanil, μg/kg), and PCA setting (with or without basal infusion). Postoperative NRS at rest and when coughing were recorded. Adverse events occurring prior to discharge were also collected from the hospital chart.

2.6 Statistical analysis Statistical analysis was performed using the SPSS statistical software package (SPSS Inc., Chicago, IL). Continuous variables are expressed as mean ± standard deviation(SD) or medians with interquartile range and categorical variables as numbers and percentages. Between-group differences were evaluated using the independent t test or Mann-Whitney U test for continuous variables and the χ2 test or Fisher exact test for categorical variables, as appropriate.

Eligibility Criteria:
Inclusion Criteria:

* Aged 18 years old and above
* Underwent elective laparoscopic colorectal procedures
* Received patient controlled intravenous analgesia postoperatively

Exclusion Criteria:

* Chronic opioid use
* Converted to open
* Admitted to ICU
* PCA regimens other than sufentanil
* PCA used shorter than 48 hours
* Incomplete postoperative opioid usage record