Materials and methods
vomit, nausea, neuromuscular blockade, drowsiness, 11/11/2021, nausea and vomiting, vomiting, pain, dizziness, headache, Nausea, PONV
ADVERSE EFFECTS, HEART, -11, NEUROMUSCULAR BLOCKADE
This prospective, randomized, multicenter, double-blinded trial enrolled patients scheduled to undergo surgery under general anesthesia at university hospitals. The patients were recruited between January 2022 and December 2022. All patients were expected to receive intraoperative antiemetics or saline. The study design was approved by the Institutional Review Boards of the Hallym University Chuncheon Sacred Heart Hospital (IRB no. 2021-11-002), Wonju Severance Christian Hospital (IRB no. CR121091), Gangneung Asan Hospital (IRB no. GNAH 2022-01-002), and Kangwon National University Hospital (IRB no. 2021-09-014). Written informed consent was obtained from each participant before the administration of any study drug. This trial was registered at the Clinical Research Information Service (cris.nih.go.kr, 11/11/2021, KCT0006749) and conducted in accordance with the Declaration of Helsinki.The participants were adults aged ≥ 20 years scheduled to undergo surgery under general anesthesia classified as American Society of Anesthesiologists physical status I or II and determined to have two or fewer risk factors for PONV. The risk of PONV was calculated based on six risk factors: female sex, surgery with a high risk of nausea and vomiting, history of PONV, non-smokers, younger age (age < 50 years), and postoperative use of opioid analgesics [The computer-generated random allocation sequence was created by an independent investigator with a 1:1:1 allocation and random block sizes; the group assignment was prepared by the enrolling anesthesiologist in sealed opaque envelopes. The enrolling anesthesiologist was not the same person as the treating anesthesiologist. The envelopes were opened before induction of anesthesia, and the drugs were prepared by an independent nurse who was not participating in any other part of the study. Participants and outcome assessors were blinded to group allocation. Patients in group C received intravenous saline (2 mL) at the end of the surgery, those in group R received intravenous ramosetron (0.3 mg; 2 mL) (Nasea®, Daiichisankyo.co.kr, Seoul, Republic of Korea) at the end of the surgery, and those in group DR received a combination of intravenous dexamethasone (5 mg; 1 mL) before the induction of anesthesia and intravenous ramosetron (0.3 mg; 2 mL) at the end of the surgery [All patients were allowed to consume solid food for up to 8 h before the surgery and water for 2 h before the surgery. Standard monitoring, including limb lead electrocardiography, pulse oximetry, noninvasive blood pressure measurements, end-tidal anesthetic gas concentration measurements, and capnography, was performed when the patient arrived in the operating room. Anesthesia was induced by administering 1.5–2.0 mg/kg of propofol and 0.5–0.8 mg/kg of rocuronium bromide intravenously. Endotracheal intubation was performed following 2–3 min of mask ventilation with 100% oxygen. Anesthesia was maintained with 1.5–3% sevoflurane and air in oxygen (fraction of inspired oxygen: 0.5). The administration of sevoflurane was discontinued, and neuromuscular blockade was antagonized via the intravenous administration of a combination of 0.3 mg/kg of pyridostigmine and 0.008 mg/kg of glycopyrrolate at the end of the surgery. Extubation was performed when the patients fully regained consciousness. All participants received no opioids during the operation.The demographic data, duration of anesthesia, and duration of surgery were recorded for each patient. All episodes of PONV were recorded during the first 48 h following emergence from general anesthesia at the following time intervals: 0–1, 1–6, 6–24, and 24–48 h. Nausea was defined as a subjectively disagreeable sensation accompanying the urge to vomit, and vomiting was defined as the forceful ejection of gastric contents from the mouth.The severity of nausea was assessed using an 11-point verbal numerical rating scale (VNRS), with the scores ranging from 0 to 10, where a score of 0 indicates no nausea and a score of 10 indicates the worst nausea imaginable. Based on the VNRS scores, the severity of nausea was classified as mild (1–3), moderate (4–6), and severe (7–10). These assessments were performed in conjunction with the PONV assessments. The rescue antiemetic, 10 mg of metoclopramide or 0.3 mg of ramosetron, was administered intravenously for the treatment of severe nausea or two or more emetic episodes or upon request from the patient. If PONV persisted after the administration of the rescue antiemetic, 4 mg of ondansetron was administered intravenously. The frequency of rescue antiemetic administration was also recorded. The patients were instructed to rate the severity of pain during the 48-h postoperative study period using an 11-point VNRS similar to that used in the assessment of the severity of nausea. An intravenous bolus dose of 30 mg of ketorolac or 20 mg of nefopam was administered upon request from the patient or when the VNRS pain score was ≥ 5. The frequency of rescue analgesic administration was recorded. In addition, data regarding the incidence of adverse effects, such as dizziness, headache, and drowsiness, were also collected. All data were recorded independently by an anesthesiologist who was blinded to the group allocation of the patients.