The significant finding in this study is that administration with penehyclidine after anesthesia induction significantly attenuated incidence and severity of both postoperative oculocardiac reflex and postoperative nausea and vomiting in the patients with strabismus surgery. Penehyclidine should be considered as an effective intervention for the prevention of intraoperative oculocardiac reflex and postoperative nausea and vomiting in strabismus surgery.
PONV is a common complication after general anesthesia for surgery patients including those who undergoing strabismus surgery. The risk factors for the development of PONV include patient-related factors, anesthetic techniques, and type of surgery (17, 18). It is well known that female, non-smokers, PONV or motion sickness history, and the use of opioids are the most common risk factors(18). The inhalational anesthetics, ketamine, and etomidate increase the incidence of PONV, while the use of propofol, midazolam and free fluid infusion technique are believed to reduce its incidence(1, 19). Also, PONV risk is affected by different kinds of surgeries including strabismus surgery. For underaged patients, duration of surgery ≥ 30 min, age ≥ 3 years and receiving strabismus surgery are all independent risk factors of PONV (20, 21). Many drugs have been used for the prevention or treatment of PONV. The most widely used antiemetic drugs are 5-hydroxytryptamine (5-HT3) receptor antagonists. The NK-1 receptor antagonists, corticosteroids, butyrophenone and antihistamines are also recommended. However, Each kind of antiemetic drugs raises different concerns just like the risk of QT prolongation in 5-HT3 receptor antagonists and the effect on postoperative infection as well as blood glucose levels in corticosteroids (21, 22). Here in this study, we demonstrated that penehyclidine, an anticholinergic agent, significantly reduced PONV in strabismus surgery patients.
Consistent with previous reports that showing 38 ~ 68.2% PONV incidence in strabismus surgery, we found 54.8% of overall PONV incidence in normal saline group in this investigation. We also found that the patients showed a significant higher PONV incidence within 6 h after strabismus surgery. Notably, we demonstrated that administration of penehyclidine after anesthesia induction pronouncedly attenuated PONV incidence in patients with strabismus surgery. The severity of PONV was mitigated and the PONV incidence was significantly reduced in the underaged and adult male patients as well as in the adult female patients following penehyclidine administration.
Unexpectedly, we also found a significant effect of penehyclidine on the attenuation of oculocardiac reflex during strabismus surgery though that penehyclidine was previously considered as having no obvious effect on heart rate (12). Oculocardiac reflex is observed frequently in strabismus surgery with an incidence of 14 ~ 90% (4). Once stimulated by manipulation, the ophthalmic branch of the trigeminal nerve transports the sensory message to central nervous system, thereby causing impulses to exit the brainstem and transmit to the sinoatrial node and activate the vagal motor response, and ultimately leading to sinus bradycardia, atrioventricular block, ventricular ectopy, ventricular fibrillation, hypotension, or even asystole (5). Thus, prevention and management of OCR is important. Several approaches have been applied to decrease the incidence of OCR. Immediately pausing surgery can suspend the reflex through removal of pressure to the eyeball or extraocular muscles; however, repeated pauses may disturb the process of surgery (5). Pretreatment with atropine or glycopyrrolate can attenuate the negative effect of vagus nerve on heart rate during OCR through blocking peripheral type 2 muscarinic receptors of the heart; however, atropine or glycopyrrolate may result in undesirable dysrhythmia such as sinus tachycardia which may diminish cardiac output (5, 23). In this study, an overall OCR incidence of 77.9% was found in strabismus surgery patients while administration with penehyclidine significantly attenuated OCR. Penehyclidine reduced overall OCR incidence, and reduced the OCR severity as indicated by requirement for atropine to rescue. However, it is not clear whether the effect of penehyclidine on OCR is caused by its intrinsic type 2 muscarinic receptor block effect.
The main side effects of penehyclidine include dry mouth and central anticholinergic syndrome, similar to other anticholinergics (15). Moreover, its central sedative effect sometimes delays anesthesia recovery. In our investigation, 10 µg·kg− 1 with an upper limit to 0.5 mg penehyclidine was used. The anesthesia recovery, as indicated by the time to extubation and the time staying post-anesthesia care unit, was not delayed in penehyclidine group compared to normal saline group. No patient complained of severe dry mouth and no patient developed central anticholinergic syndrome postoperatively. These may possibly be explained by limited maximal dose difference, and our patients undergoing minor surgery could drink free after surgery (24).
The anesthesia scheme design enhanced the strengths of this study. Agents including midazolam, etomidate, inhalational anesthetics or neostigmine were not used because potential effects on PONV. Besides, the randomization and double-blinded technique were strictly carried out during the investigation. As randomization was achieved by lottery method, patients allocated into the two groups were not equal. In subgroup analysis, the sample size of the subgroups also appeared imbalanced. In order to get more reliable outcomes, a stratified random sampling method is more suitable for pre-designed subgroup analysis.