| BACKGROUND:Postoperative nausea and vomiting(PONV)is a common complication after general anesthesia.The incidence of PONV is generally between 20%and 30%,whereas the reported incidence of PONV after thyroidectomy can be as high as 60%to 76%without prophylactic antiemetics.From the patient’s point of view,PONV increases patient-related discomfort and thus results in poor patient satisfaction.Moreover,PONV is a risk factor for postoperative bleeding,which may lead to the formation of neck hematoma after thyroid surgery and airway obstruction and result in increased medical costs,slower recovery,prolonged postanesthesia care unit(PACU)stay,delayed discharge or even unexpected readmission.Although administration of antiemetics is one of the most common treatment strategies for nausea and vomiting,they can lead to an increased risk of adverse drug reactions and side effects such as dizziness,QT prolongation,and increased cost of hospitalization.Several clinical studies have found that antiemetics can only reduce the risk of PONV by 25%to 66%,which means that antiemetics are only partly effective.Because nonpharmacologic antiemetic strategies,such as transcutaneous electrical stimulation of the acupuncture point Neiguan,chewing gum,and dry ginger powder capsules,have the advantages of low cost and favorable patient acceptability,they have recently gained increasing attention.Although hypercapnia directly inhibits myocardial contractility,it ultimately increases cardiac output by indirectly enhancing the excitability of the sympathetic nerves.Recently,some studies showed that gastrointestinal mucosal hypoperfusion is associated with PONV.Studies have shown that mild hypercapnia can improve gastrointestinal tissue perfusion and oxygenation by dilating blood vessels,increasing cardiac output and favoring unloading of oxygen.We hypothesized that in patients scheduled for elective thyroidectomy during general anesthesia,mild hypercapnia might reduce the incidence of PONV.Considering all available evidence,studies on the use of mild hypercapnia to decrease the incidence of PONV have yielded controversial results,resulting in confusion among clinicians on the effectiveness of this intervention.To date,the impact of intraoperative mild hypercapnia on PONV in non-abdominal surgery has not been defined.We therefore performed a pilot randomized controlled trial to compare mild hypercapnia(45-50 mm Hg)with normocapnia(30-35 mm Hg)in terms of the incidence of PONV after thyroidectomy and to test the feasibility of a future definitive trial.METHODS:Study designThis randomized controlled trial was registered on chictr.org.cn(number:ChiCTR1900023997;principal investigator:Dr K.-X.L.;date of registration:June 21,2019).Approval was gained from the Medical Ethics Committee of Nanfang Hospital,Southern Medical University,and Written informed consent was obtained from all patients before enrollment.The trial was conducted between July 24,2019,and November 22,2019 in the Department of Anesthesiology,Nanfang Hospital,Southern Medical University.This manuscript adheres to the applicable CONSORT guidelines.PatientsPatients between 18 and 65 years of age with American Society of Anesthesiologists(ASA)physical status Ⅰ or Ⅱ and with low or medium risk of PONV who were undergoing elective thyroid surgery were enrolled.Exclusion criteria were known hypersensitivity to antiemetic drugs;documented significant systemic diseases;use of antiemetic drugs,opioids or glucocorticoids within 3 days before surgery;participation in another clinical trial;and pregnancy or breast-feeding.ProtocolIn this single-center,parallel-group pilot trial,patients undergoing elective thyroidectomy were randomly assigned to the intraoperative normocapnia(end-tidal carbon dioxide tension 30-35 mmHg)or mild hypercapnia group(end-tidal carbon dioxide tension 45-50 mmHg).In the mild hypercapnia group,the soda lime carbon dioxide absorbent,which remained in the normocapnia group,was removed from the anesthesia machine.The ventilation protocol consisted of volume-controlled mechanical ventilation at a fraction of inspired oxygen of 0.4-0.6,respiratory rate at 6-20 breaths/min,tidal volume of 6 to 8 ml/kg,inspiratory to expiratory ratio of 1:2,and 1-3 l/min fresh gas flow adjusted to maintain an end-tidal partial pressure of carbon dioxide of either 30-35 mmHg or 45-50 mmHg.All patients received lung-protective ventilation.Extubation was performed after the patient woke up inthe operation room or postanesthesia care unit(PACU).If extubation did not occur in the operating room,the patient continued mechanical ventilation in the PACU and was managed according to the PACU doctor’s intention.OutcomesThe primary outcome was the incidence of postoperative nausea and vomiting within the first 24 hours after surgery.The primary feasibility objectives were as follows:(ⅰ)to confirm the rate of PONV after thyroidectomy and to adjust sample size for a further definitive trial;(ⅱ)to refine and test the trial protocol for a larger randomized controlled study;(ⅲ)to access the recruitment rate and retention rate.A high recruitment rate(70%or greater)and retention rate(90%or greater)will be required to proceed a future definitive study.Secondary endpoints included postoperative pain scores,rescue antiemetics,supplementary analgesics,duration of PACU stay,duration of hospitalization,duration of hospitalization after surgery,time to extubation,time to first bowel sounds,time to first food intake,time to first flatus,time to first resume walking and postoperative complications.Statistical analysisWe calculated that 111 patients per group would provide 80%power to detect a 50%reduction of PONV at a two-sided alpha level of 0.05,assuming a 32%rate of PONY in the normocapnia group and 16%in the mild hypercapnia group.Considering a 10%drop-out rate,we therefore planned to recruit 244 patients.To guide a future main study,a pilot trial on a sample of 122 patients was conducted.RESULTS:Between Jul 24,2019,and Nov 22,2019,of 142 patients enrolled,124 were randomly assigned to receive either mild hypercapnia(n=62)or normocapnia(n=62).The recruitment rate was 87.3%(95%CI 80.8-91.9%),and the retention rate was 98.4%(95%CI 93.9-99.9%).The baseline characteristics were similar between the two groups.Intraoperative observationsIn the mild hypercapnia group,the soda lime carbon dioxide absorbent was removed from the anesthesia machine.The median(IQR)fraction of inspired carbon dioxide(FiCO2)values was 20.4(17.4-22.2)mm Hg and 0.0(0.0-0.0)mm Hg,respectively(P<0.001).The mean PetCO2 was 46.7(SD 1.2)mm Hg in the patients assigned to the mild hypercapnia group and 31.8(SD 1.3)mm Hg in those assigned to the normocapnia group(P<0.001).The results of the blood gas analysis are presented in Table 2.The pH was significantly lower in the hypercapnia group than in the normocapnia group(7.29(0.04)vs.7.40(0.04),P<0.001).Patients in the mild hypercapnia group had higher PaCO2 than those in the normocapnia group(52.0(48.3-55.0)mm Hg vs.37.0(33.0-38.0)mm Hg,P<0.001).Patients in the mild hypercapnia group had lower mean arterial pressure(MAP)than those in the normocapnia group(68(8)mm Hg vs.79(9)mm Hg,P<0.001),and use of ephedrine during anesthesia was higher in the mild hypercapnia group as compared with the normocapnia group(16.7%vs.11.3%,P<0.001).Postoperative observationsPONV developed in 31.7%(95%CI 21.3-44.3%)of the 60 subjects who received mild hypercapnia and in 16.1%(95%CI 8.8-27.4%)of the 62 who received normocapnia(P=0.044).The rate of PONV was higher in the mild hypercapnia group than in the normocapnia group from 0 to 2 hours(12(20.0%)vs.9(14.5%),P=0.422),2 to 6 hours(7(11.7%)vs.1(1.6%),P=0.031)and 6 to 24 hours(4(6.7%)vs.2(3.2%),P=0.436)after surgery.The incidence of nausea and the incidence of vomiting were higher in the mild hypercapnia group,although the difference was not statistically significant.The time to first food intake was earlier in normocapnia group,but the difference was not clinically meaningful(P=0.04).There were no differences regarding the other secondary outcome measures between the groups.CONCLUSIONS:In this pilot study,compared with normocapnia,mild intraoperative hypercapnia did not decrease several PONV outcomes after thyroidectomy.A future definitive study with comparable intraoperative blood pressure and reasonable ventilation management strategy may be required to further explore this issue. |
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