PONV is one of the most common complication and the most unpleasant aspect after thyroid surgery under general anesthesia. This complication can delay patient discharge from the hospital and increase the cost of care[12, 13]. Thyroid surgery, specifically is associated with a high incidence of PONV. The main cause of the high incidence of PONV after thyroid surgery is not thoroughly clear, but it is thought to result from the hyperextension of the neck and strong vagal stimulation [14]. Hyperextension of neck posture might lead to cerebral blood flow disorders which could cause central nausea and vomiting[15]. And strong vagal stimulation by surgical handling of neck structures might exacerbated the incidence of PONV [16, 17].
Muscarinic receptors are involved in PONV by various mechanisms [18, 19]. Golding et al. [20] reported that M3 and M5 acetylcholine receptors have been shown to reduce motion sickness, a risk factor of PONV. The vestibular system is densely packed with M1 receptors, and cholinergic transmission from the vestibular nuclei to the central nervous system centers and from the medullary reticular formation to the vomiting center is blocked by anticholinergics. Additionally, in thyroid surgery, surgical handling of neck structures strongly stimulates the vagus nerve in neck [21]. Anticholinergics have been shown to be effective to prevent PONV, and the recommended anticholinergic drug is scopolamine [7, 9]. Due to its short half-life, scopolamine is used as a transdermal patch before surgery.
Penehyclidine (2-hydroxyl-2-cyclopentyl-2-phenyl-ethoxy) is a new long-acting anticholinergic drug with anti-muscarinic and anti-nicotinic activities that has potent central and peripheral anticholinergic activities. It is widely used as a pharmacologic agent for organic phosphorus poisoning and preoperative medication, but its effect in PONV was unclear. Penehyclidine has greater selectivity for muscarinic 1(M1) and muscarinic 3 (M3) subtypes of acetylcholine receptors but no effect on muscarinic 2 (M2) subtype of acetylcholine receptors[22]. Its effect on PONV was expected given its mechanism of action. Previous reports showed that penehyclidine mitigated the incidence of PONV in patients after strabismus surgery[10] and gynecological laparoscopic surgery[23]. In our study, we also found that penehyclidine reduced PONV in patients undergoing thyroid surgery. In these surgeries, the draw reaction is a routine operation which may be related to the higher incidence of PONV.
The privious studies demonstrated that propofol prevent the incidence of PONV during the early 0–2 h postoperative period rather than late[3, 24],which is consistent with the results of our study. Our analysis shows that patients receiving TIVA had a higher incidence of PONV in the late postoperative phase, starting 2 h after surgery.
TIVA has been documented to prevent PONV after thyroid surgery. Apfel et al. [25]suggested that the risk factors between early PONV (< 2 h) and late PONV (2–24 h) are differ, inhalation or TIVA was not a risk factor of late PONV. A longer-acting antiemetic drug might be necessary to prevent late PONV after TIVA[24, 26]. Penehyclidine has a long elimination half-life (10.4 ± 1.22 h) which is longer than that of ondansetron (3.5 h) or granisetron (4.9 h) or ramosetron (9 h)[27, 28]. our study suggests that penehyclidine effectively reduced the late incidence of PONV (2–24 h) than early PONV (0–2 h) in patients after TIVA.
The main side effects of penehyclidine are dry mouth, headache and central anticholinergic syndrome. In the present investigation, none of the patients presented with central anticholine syndrome and there was no difference between groups in dry mouth, headache. These may possibly be explained by the limited dose of 0.5mg penehycline.
Potential risk factors contributing to PONV, such as etomidate and neostigmine were not administrated in in thyroid surgery. The gender of patients was mostly female, which was consistent with previous reports (female-to-male ratio 2–4:1) [29]. Besides, we strictly performed the randomization and double-blinded technique during the study.
A limitation of the current study should be noted. we anticipated that there would be about a 30% reduction between the two groups before our study. However, the actual reduction in overall PONV incidence was 24% (36% in TIVA group vs 12% in penehycline group, P = 0.005) during the 24 h after surgery. But the relative reduction rate of 30–40% in general PONV study is considered clinically relevant, the acquisition of a relative risk reduction of 67% in our study could be considered clinically significant [21, 30]. However, this operation was performed as a TIVA with propofol infusion. How high if using inhalational agents is unknown. Further studies are needed to research penehyclidine in more patients at more diverse surgical settings using different anesthetic techniques.