In this study, the baseline heart rate and well-known risk factors of PONV after general anesthesia showed significant associations with the PONV incidence in patients undergoing orthopedic surgery under spinal anesthesia. Additionally, dexamethasone and 5-HT3R antagonist showed significant association with decreased PONV incidence after spinal anesthesia. Furthermore, there was a significant interaction between their combination and high PONV risk, suggesting the need for multimodal PONV prophylaxis in patients with high-risk PONV under spinal anesthesia.
Our result suggested that four risk factors for PONV included in the Apfel score could be still valid for predicting PONV after spinal anesthesia [7]. The recent prospective observational study reported female sex and a history of PONV as significant risk factors for PONV after spinal anesthesia [12]. Although this study did not show a significant association between smoking and PONV incidence due to a lack of smokers [12], our study also showed a significant association between them. The effect of postoperative opioid on PONV after spinal anesthesia could be estimated from previous studies regarding opioid-sparing analgesia in spinal anesthesia [13], and postoperative opioid also showed a significant association with PONV incidence after spinal anesthesia in our study. The predictive power of the Apfel score for PONV after spinal anesthesia should be evaluated through prospective studies.
We also investigated several possible risk factors of PONV in spinal anesthesia, distinguished from general anesthesia [10]. One prospective study reported addition of vasoconstrictor to the local anesthetic, baseline heart rate ≥ 60 beats/min, intraoperative hypotension, and peak block height ≥ T5 as significant risk factors for nausea and vomiting during spinal anesthesia [14]. However, this study investigated only intraoperative nausea and vomiting, not postoperative. In our study, only baseline heart rate ≥ 60 beats/min showed significant association with PONV incidence after spinal anesthesia. Sympathetic blockade by spinal anesthesia causes unopposed vagal effect, contributing to PONV incidence [10]. It can be presumed that unopposed vagal effect caused by spinal anesthesia have been obscured in patients with preoperative bradycardia due to their adaptation to parasympathetic hyperactivity [15]. Intraoperative hypotension has also been known to cause nausea and vomiting during spinal anesthesia via brain stem and gut ischemia [10]. However, considering the short duration of intraoperative hypotension and supplemental oxygen in our patients, it would have been difficult to cause brainstem or gut ischemia enough to cause PONV. Since we did not add vasoconstrictors to local anesthetics, we could not investigate its effect on PONV incidence. Moreover, several sedatives used for intraoperative sedation, such as dexmedetomidine, midazolam, and propofol, have been reported to reduce PONV in general anesthesia [6, 16–18]. However, we could not find significant association between intraoperative sedation using dexmedetomidine or midazolam and PONV incidence after spinal anesthesia. A wide variation in dosage of sedatives and duration of its administration in our study might have affected the negative result. Additionally, different from morphine, intrathecal fentanyl has been reported to have no effect on PONV incidence, and our study was also consistent with the previous result [10]. Further studies on the risk factors of PONV in spinal anesthesia are required to better predict PONV after spinal anesthesia.
Our study also highlighted the need for multimodal PONV prophylaxis in spinal anesthesia. To the best of our knowledge, there seems to be limited evidence for multimodal PONV prophylaxis in spinal anesthesia [19, 20]. Previous randomized controlled trial (RCT) reported that the combination of metoclopramide with dexamethasone was more effective in preventing PONV compared to dexamethasone alone [21]. However, this study included patients undergoing general or regional anesthesia [21], and metoclopramide is currently not recommended as a first-line prophylactic agent for PONV [6]. There has also been report of the prophylactic effect of the combination of dexamethasone with droperidol on PONV [22]. However, the use of droperidol is significantly limited in many countries, due to its risk of sudden cardiac death [6]. Another RCT reported that the combination of ondansetron with dexamethasone significantly reduced the incidence of postoperative nausea in patients undergoing cesarean section compared to each single agent [23]. However, this study did not consider other risk factors that could affect the incidence of PONV, and the observation period of the PONV incidence was only during the stay in the recovery room [23]. Although our present study used a retrospective study design, we included a large cohort of patients undergoing spinal anesthesia and also attempted to adjust several risk factors of PONV after spinal anesthesia. In our study, dexamethasone, 5-HT3R antagonist, and their combination showed a significant association with decreased PONV incidence. Furthermore, there was a significant interaction between their combination and high PONV risk, suggesting a significant effect of multimodal PONV prophylaxis, including dexamethasone and 5-HT3R antagonist, in the high-risk group. Therefore, optimal PONV prophylaxis according to the predicted risk of PONV would be required in patients receiving spinal anesthesia.
Our study results should be interpreted cautiously for several reasons. First is the inherent limitation of our study’s retrospective design; unmeasured or unknown covariates could have affected our results. Our data sources lacked important clinical details, such as history of motion sickness and amount of postoperative opioid consumption. Additionally, the reliability of PONV incidence determined from our nursing documentation could have affected our findings. Although PONV incidence was routinely recorded in our institution, mild or transient nausea, which patient did not complained of, was not likely to be recorded in medical records. Second, it is difficult to generalize our findings since our results were obtained from a single institution. Third, we could not include intraoperative PONV incidence in the analysis due to its insufficient records. Further studies are required on the association between intraoperative nausea and vomiting and PONV in spinal anesthesia. Finally, we could not analyze the use of recue antiemetic that could reflect the severity of PONV, due to our routine use of 5-HT3R antagonist on the first day postoperatively. Despite these limitations, to the best of our knowledge, this study is the first to investigate the association between several factors and PONV incidence in a large cohort of patients receiving spinal anesthesia.