Oral Mosapride Can Provide Additional Antiemetic Efficacy Following Total Joint Arthroplasty Under General Anesthesia

A Randomized, Double-blinded Clinical Trial

Jinwei Xie; Yingchun Cai; Jun Ma; Qiang Huang; Fuxing Pei

Disclosures

BMC Anesthesiol. 2020;20(297) 

In This Article

Methods

Study Design

This prospective, randomized, clinical trial was performed on patients undergoing primary total hip or knee arthroplasty between November 2017 and December 2018. Institutional review board approval (2012–268) was obtained before the enrollment of patients. All patients provided written informed consent and research authorization before surgery. The study was conducted in compliance with the recommendations of the CONSORT Statement and the Declaration of Helsinki. The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896).

Participants

Eligible patients included those at least 18 years old who were at risk of PONV (at least 1 score of Apfel), and scheduled for primary total hip or knee arthroplasty for end-stage joint diseases such as osteoarthritis, development dysplasia of hip, and osteonecrosis of the femoral head. Exclusion criteria included a history of intolerance of any drugs used in the current study, administration of another anti-emetic drug or systemic steroid within 24 h before surgery, allergy to experimental drugs or history of adverse reactions, diabetes with poor blood glucose control, history of steroid or immunosuppressive drug use within the previous 6 months, history of cardiac disease such as heart failure, heart block, ventricular arrhythmia or severe impairment of bowel motility, renal function or hepatic function.

Randomization and Treatment

Patients in this double-blind study were randomly allocated into three groups using a computer-generated randomization list in a 1: 1: 1 ratio. A random allocation sequence concealed in opaque sealed envelopes only opened before surgery. The control group received 2 ml of normal saline during anesthesia induction, followed by oral placebo at 3 h before surgery and three times per day after surgery. The Dexa group received 10 mg of dexamethasone (in 2 ml) during anesthesia induction, as well as oral placebo at 3 h before surgery and three times per day after surgery. The Mosa+Dexa group received 10 mg of dexamethasone (in 2 ml) during anesthesia induction, as well as 5 mg of oral Mosapride at 3 h before surgery and three times per day after surgery. Dexamethasone was administered intraoperatively by the anesthesiologist and oral drugs were given postoperatively by nurses who were not involved in the study. Patients, surgeons, data collectors and analysts were blinded to group allocation.

Anesthesia and Perioperative Pain Management

All surgeries were performed under general anesthesia by the same surgeons; standard medial parapatellar arthrotomy was performed for total knee arthroplasty, and the posterolateral approach was used for total hip arthroplasty. A cemented posteriorly stabilized prosthesis was implanted in all total knee arthroplasty patients, and cementless acetabular and femoral components were implanted in total hip arthroplasty patients.

All patients received the same anesthetic regimen and multimodal pain management protocol. Cefuroxime (1.5 g) was given intravenously as prophylactic antibiotic prior to incision. Sufentanil (0.2 μg/kg) propofol (2 mg/kg), atracurium (1 mg/kg) and midazolam (2 mg) were used for anesthesia induction. Then sufentanil (0.1 μg/kg), atracurium (0.5 mg/kg) and sevoflurane (1–3%) were used to maintain anesthesia during surgery. After prosthesis insertion, propofol (4 mg per kg per h) and remifentanil (0.1 μg per kg per min) were used to maintain anesthesia. Anesthetic drugs were discontinued before wound closure. At the end of surgery, 8 mg ondansetron was administered intravenously to all patients.

After prosthesis insertion, a periarticular infiltration of 200 mg ropivacaine (100 mg per 10 ml) in 60 ml of normal saline was injected all around the capsule before closure. A dose of 40 mg of parecoxib was injected intravenously to manage pain. Postoperative pain control consisted of 50 mg of oral voltaren (Diclofenac Sodium Sustained Release Tablets) and 10 mg of oxycodone every 12 h. Breakthrough pain was recorded using a Visual Analgesic Scale (VAS) score that ranged from 0 (no pain) to 10 (most severe). If the VAS score was > 6, 50 mg of pethidine was given as an intramuscular injection when required, up to every 6 h. No nerve block or intravenous patient-controlled analgesia was utilized perioperatively.

Outcome Measurements

The primary outcome variables were the incidence of PONV, severity of PONV and complete response. Secondary outcome variables included time until first defecation and ambulation, postoperative appetite score, patient satisfaction score and length of hospital stay. A blinded clinical investigator reviewed the diagnosis and medical histories of patients and prospectively collected demographic data and surgical information. The investigator also recorded all episodes of nausea and vomiting, severity of nausea, requirement for anti-emetic rescue, and complete response during four postoperative periods (0–6, 6–12, 12–24 and 24–48 h). Nausea was defined as a subjective unpleasant sensation associated with awareness of the urge to vomit, and vomiting was defined as the forceful expulsion of gastric contents from the mouth.[16] The incidence of nausea and vomiting was determined in each of the four periods and during the entire study by calculating the proportion of patients who experienced PONV. In order to avoid double counting, the patients experienced both nausea and vomiting would be counted as episode of vomiting. Following institutional guidelines, 10 mg of intramuscular metoclopramide was used as a first-line anti-emetic rescue treatment when patients experienced two or more episodes of PONV within 2 h. This was followed by 4 mg of intravenous ondansetron when two consecutive boluses of metoclopramide alone, delivered 30 min apart, were ineffective.

We used a standardized scoring algorithm to classify the severity of PONV on a 4-level scale during the 48-h observation period. Complete response was defined as no additional PONV or no requirement for anti-emetic rescue. Mild PONV described the occurrence of mild nausea or one episode of vomiting caused by exogenous stimulus (drinking or movement). Moderate PONV referred to when the patient vomited up to two times or experienced nausea that required anti-emetic rescue only once. Patients were classified as having severe PONV if they suffered more than two emetic episodes or required more than one dose of rescue anti-emetic.[17,18]

The same blinded investigator also recorded the time until first defecation, ambulation and length of hospital stay, and evaluated appetite score on postoperative days 0–2 as follows: 1 point, lower appetite than preoperatively; 2 points, same appetite as preoperatively; and 3 points, more appetite than preoperatively. The same investigator assessed patient satisfaction before discharge using a VAS score that ranged from 0 (extremely dissatisfied) to 10 (very satisfied). During the perioperative period, all the patients would be carefully evaluated for side effects and cardiac complications such as atrioventricular block, or QT interval prolongation with the use of electrocardiogram if necessary.

Statistical Analysis

We performed a priori power analysis based on our preliminary results showing that PONV incidence was 49% in patients receiving ondansetron prophylaxis alone after total joint arthroplasty [unpublished data]. We calculated that 228 patients (76 in each arm) were required to detect a 50% reduction in PONV incidence at an alpha level of 0.05 and a power of 0.9 using a two-sided test. To allow for exclusions and dropouts, we aimed to enroll 246 patients.

Inter-group differences in categorical variables such as incidence of PONV or proportion of complete response were assessed for significance using the chi-square or Fisher's exact tests. When differences were significant, multiple comparisons between groups were performed using a Bonferroni-corrected post hoc test. Inter-group differences in continuous variables were assessed for significance using either one-way ANOVA, in the case of body mass index, length of hospital stay, time until first defecation or ambulation; or the Wilcoxon signed-rank test, in the case of appetite and patient satisfaction scores. When differences were significant, multiple comparisons between groups were performed using a post hoc Tukey test. Differences associated with p < 0.05 were considered statistically significant. All statistical analyses were conducted in SPSS 21.0 (IBM, Chicago, IL, USA).

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