This randomized prospective parallel study was performed in accordance with the Declaration of Helsinki. It was approved by the Institutional Review Board of the third affiliated hospital of Sun Yat-sen University (approval number: [2016]2-184) and registered with the Chinese Clinical Trial Registry at www.chictr.org on February 7, 2017 (registration number: ChiCTR-IOR-17010561). This manuscript adhered to the applicable CONSORT 2010 checklist.
All patients who were scheduled for elective laparoscopic colorectal resection from March 1, 2017 to February 29, 2018 were considered for inclusion. The inclusion criteria were as follows: (i) age 18–80 years, (ii) American Society of Anesthesiologists Physical Status I to III, (iii) provided informed written consent. Patients who met any of the following criteria were excluded: (i) comorbid intestinal obstruction and gastric emptying disorder; (ii) diabetes; (iii) body mass index >30 kg/m2; (iv) severe renal insufficiency or long-term use of potassium-sparing diuretics; (v) history of neurological or mental illness; (vi) patients with hyperkalemia or hypokalemia. Patients who were transferred to open surgery or underwent colostomy during the operation were excluded from the final analysis.
Patients were randomly assigned to control, placebo, and case groups according to computer-generated random numbers. In the control group, patients were fasted from midnight; in the placebo group, patients were fasted from midnight and received carbohydrate drinks (5–6 mL/kg containing 14.2% carbohydrates) 2–3 h before surgery; and in the case group, patients were fasted from midnight and received carbohydrate drinks containing potassium supplementation (5–6 mL/kg containing 14.2% carbohydrates and 1 g of potassium) 2–3 h before surgery. All the drinks were prepared in bottles prepared by the hospital pharmacy with the same appearance and were distributed by the same trial assistant who was not involved in the follow-up or assessment. The random number was sealed in an envelope until the morning of surgery. All patients were fasted from solid food from midnight before surgery. To maintain blinding, the anesthetist was not involved in the follow-up or assessment. Patients received standardized care during the perioperative period.
Sample size
This study was a randomized clinical trial with three parallel groups. The main outcomes were the incidence rates of preoperative hypokalemia. The following formula was used to calculate the sample sizes:
According to our pilot trial, which resulted in pA = 0.88, pB = 0.77, and pC = 0.41, 40 participants were required in each group for a power of 80% and a two-tailed p-value of 0.05 was considered as statistically significant. A final sample size of n = 44 was determined based on an assumed dropout rate of approximately 10%; therefore, 44 patients were enrolled in each group, and the total number of patients was 132.
Procedures
Anesthesia was induced with intravenous midazolam (0.03 mg/kg), fentanyl (3–5 μg/kg), propofol (1.5–2.5 mg/kg), and cisatracurium (0.2 mg/kg) and maintained with sevoflurane (0.7–1.2 minimum alveolar concentration), remifentanil (0.05–0.15 μg · kg · min), and cisatracurium (0.1 mg · kg · h). Ventilation was controlled with a tidal volume of 8–10 mL/kg with end tidal CO2 of 35–45 mmHg. The volume was admitted according to central venous pressure (maintained at 5-12cmH2O).
Potassium was measured by obtaining venous blood before anesthesia induction. If the blood potassium was less than 2.8mmol/L, potassium would be supplemented intravenously before induction of anesthesia.
Standardized analgesic strategy was used for all patients. Fifteen minutes before the end of surgery, patients were intravenously infused with flurbiprofen axetil (1 mg/kg) as an analgesic and tropisetron (5 mg) to prevent vomiting. Postoperatively, patient-controlled intravenous analgesia devices containing sufentanil (2 μg/kg) and tropisetron (10 mg) were applied to all patients for 2 days.
Outcomes
The primary outcome was the incidence and severity of preoperative hypokalemia.
Normal potassium levels were defined as blood potassium levels between 3.5 and 5.5 mmol/L. Potassium levels between 3.0 and 3.5 mmol/L, more than 2.5 and less than 3.0 mmol/L, and less than 2.5 mmol/L were considered as slight, moderate, and severe hypokalemia, respectively[8].
Pre-anesthesia thirst (0, no thirst; 10, unbearable thirst), hunger (0, no hunger; 10, unbearable hunger), flavor (0, unbearable flavor; 10, tasty flavor), and anxiety scores (0, no anxiety; 10, high anxiety) were assessed using a visual analog score based on that of a previous study[10].
The other outcomes included postoperative gastrointestinal function, the time to postoperative first flatus (FFL) and first feces (FFE) and other complications. Postoperative hospitalization stays and hospitalization costs were also recorded.
Statistical analysis
The Statistical Package for the Social Sciences 21.0 (IBM Corporation, Armonk, NY, USA) was used to perform statistical analyses. Quantitative data were expressed as the mean ± standard deviation, and qualitative data and ordinal data were expressed as absolute frequencies. The one-sample Kolmogorov–Smirnov test was used to test the normality of the quantitative data. According to the distribution of quantitative data, a one-way analysis of variance or non-parametric test was used. The least significant difference method was used for further comparison among the groups. The Kruskal–Wallis test was used to compare quantitative data which was not normal distribution. For qualitative data, the chi-square test or Fisher’s exact probability test was used to compare differences. Differences were considered significant when two-tailed p-values were < 0.05. A justified p-value was used for multiple comparisons (the significance of p value should be less than 0.05/n, n means comparison frequency).