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[每周一问]No.6-Postoperative Nausea and Vomiting (PONV)
This week we'll be discussing one of the more frequent complications associated with anesthesia and surgery, postoperative nausea and vomiting. Today, we'll focus on anesthetic risk factors associated with PONV.
1.  What are some anesthetic factors that influence the incidence of PONV?
2.  In terms of premedications, what medications have been demonstrated to affect PONV?
3.  Are certain volatile anesthetics associated with a higher incidence of PONV?
4.  Is there an association with nitrous oxide and the incidence of PONV?
5.  How are the intravenous agents propofol, ketamine, etomidate, and thiopental compared in terms of PONV?
6.  What is the mechanism of the antiemetic effect of propofol?

今天，我们重点讨论与PONV相关的麻醉因素

1.  影响PONV发生率的麻醉因素有哪些？
2.  在术前药物中，什么药物明确有导致PONV作用？
3.  挥发性麻醉剂是否与PONV增加明确相关？
4.  笑气是否与PONV发生相关？
5.  从PONV方面比较静脉麻醉剂propofol, ketamine, etomidate, thiopental之间的强度。
6.  propofol镇吐作用机制是什么？

[每周一问]NO.6之参考答案
1.影响PONV发生率的麻醉因素有哪些？
与麻醉相关的影响PONV发生的因素有：
术前镇静药物的使用
麻醉方法
静脉麻醉药
笑气（有争议）
预防性使用止吐药
麻醉药用量
非去极化神经肌肉阻滞剂的拮抗
疼痛控制
运动
误吸
救治性止吐药的使用

2.在术前药物中，什么药物明确有导致PONV作用？
给于术前药物被证明在预防PONV方面存在一定效果，但是很明确，这些优点仅仅存在部分种类的药物中。地西泮证明有明确的作用，特别是在接受高PONV风险手术的小儿患者中有明确作用，比如斜视矫治和扁桃体切除术[1]。同时又意义的是，术后咪唑安定的使用也被证明可以明确减少治疗性镇吐药的使用[2]。其作用机制尚在研究中。
α2受体激动剂可乐定也证实存在阻止PONV的作用，因为其可减轻焦虑、减少麻醉剂和其他药物的使用[3]。相比之下，虽然术前给予芬太尼，比如给予5-20 μg/kg transmucosal fentanyl，与镇静相关并可减少麻醉剂的需要量，但是PONV通常均与其相关[4]。
3.挥发性麻醉剂是否与PONV增加明确相关？
虽然现代强效吸入麻醉剂与以前的药物相比可以明显降低PONV的发生，比如醚类和环丙烷类，但是没有明确的证据表明某种吸入麻醉剂优于其他麻醉剂[3]。虽然一些学者认为七氟醚或地氟醚可能与降低PONV发生率相关[3]，但是Karlson等[5]在接受乳腺手术的女性患者的开放（术前）、双盲（术后）、随机控制研究中发现，与地氟醚或七氟醚相比，在最初24小时PONV的发生率上异氟醚更低（4%比28%）。需要更进一步的研究以证实这些发现。
4.笑气是否与PONV发生相关？
PONV研究中一个代表性问题可以通过笑气举例说明，也就是说，早期研究没有能区分恶心和呕吐这两个可分离的实体。这种区分的意义可以通过近期3个独立的meta分析得到证实，表明在不用笑气的情况下，恶心发生率未见减少[6]。相比之下，在高危PONV病人中，未用笑气的患者呕吐的发生率较少[7]。
5.从PONV方面比较静脉麻醉剂propofol, ketamine, etomidate, thiopental之间的强度。
从催吐的可能性方面相比，这些镇静催眠药从小到大依次为：
propofol, thiopental, ketamine/etomidate[3]
6.propofol镇吐作用机制是什么？
作为一种烷基酚，已经证实异丙酚在作为单独的麻醉诱导剂量，特别是作为麻醉维持剂时，在小儿和成人均有降低PONV发生率的可能。然而，其短暂的镇吐作用使得其与其他用于治疗PONV的药物有所不同。除了这些优点外，其作用机制仍有待确定。迄今为止，研究表明，该机制似乎与其抗焦虑、镇静及其与5-羟色胺受体的多巴胺相互作用无关。
 
[每周一问]NO.6之参考答案[英文]

What are some anesthetic factors that influence the incidence of PONV?
A number of factors under the anesthesiologist's control can affect the incidence of PONV, including (1):
•  Use of preoperative sedation
•  Type of anesthetic technique
•  Intravenous agent use
•  Nitrous oxide use (controversial)
•  Intravenous fluid therapy
•  Prophylactic antiemetics
•  Narcotic doses
•  Antagonism of nondepolarizing neuromuscular blockade
•  Pain control
•  Motion
•  Oral intake
•  Rescue antiemetic use

In terms of premedications, what medications have been demonstrated to affect PONV?
Premedications have been demonstrated to be of some value in preventing PONV, however, these benefits are significant in only a few classes of medications. Benzodiazepines have been demonstrated to be of significant value, especially in the pediatric population undergoing procedures associated with a high incidence of PONV, i.e. strabismus repair or tonsillectomies (1). Of interest, the use of midazolam postoperatively has also been noted to significantly reduce the need for rescue antiemetics in the setting of persistent PONV (2). The mechanism for this effect is still under investigation.
The alpha-2 agonist clonidine has also been demonstrated to be of value in preventing PONV, due to its ability to minimize anxiety and to reduce the requirements for anesthetics and other medications (3). By contrast, although premedication with opioids, such as transmucosal fentanyl in doses of 5-20 µg/kg, has also been associated with sedation and decreased anesthetic requirements, PONV has been commonly associated with its use (4).

Are certain volatile anesthetics associated with a higher incidence of PONV?
Although modern potent inhalational anesthetics are associated with a significantly lower incidence of PONV than their predecessors, such as ether and cyclopropane, there is no compelling evidence that one agent is better than the others (3). Although some authors have suggested that sevoflurane or desflurane may be associated with lower incidences of PONV (3), Karlson et al. (5) noted in an open (preoperatively), double-blinded (postoperatively), randomized controlled study in women undergoing breast surgery, that the incidence of PONV for the first 24 h was lower with the more soluble isoflurane, versus desflurane or sevoflurane (4% versus 28%). Further study will be needed to confirm these recent observations.

Is there an association with nitrous oxide and the incidence of PONV?
One of the leading problems in PONV research can be illustrated with nitrous oxide, namely, that earlier investigations failed to distinguish nausea and emesis as separate entities. The value of this separation can be demonstrated through three recent independent meta analyses which noted that with the omission of nitrous oxide, no reduction in the incidence of nausea was observed . By contrast, in patients at high risk of PONV, the incidence of emesis was reduced with its omission (7).

How are the intravenous agents propofol, ketamine, etomidate, and thiopental compared in terms of PONV?
When compared as induction agents in terms of emetogenic potential, these sedative hypnotic agents can be arranged, from least to most associated, as follows: propofol, thiopental, ketamine/etomidate (3).

What is the mechanism of the antiemetic effect of propofol?
An alkylphenol, propofol has been demonstrated to be associated with a low incidence of PONV in both children and adults when used as a single induction dose, and especially when used as a maintenance agent. However, the brief action of this antiemetic property makes it an unlikely agent to be used in the treatment of PONV. Despite these beneficial actions, the mechanism of this action has yet to be established. To date, the mechanism does not appear related to anxiolysis, sedation, or interaction of the dopamine of serotonin receptors .

Question Author: Lawrence Tsen, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1.  Rose JB, Watcha MF. Postoperative nausea and vomiting in paediatric patients. Br J Anaesth. 1999;83(1):104-17.
2.  Di Florio T, Goucke CR. The effect of midazolam on persistent postoperative nausea and vomiting.Anaesth Intensive Care 1999;27(1):38-40
3.  McGoldrick KE. Postoperative nausea and vomiting. Probl Anesth 2000;12:274-86.
4.  Dsida RM, Wheeler M, Birmingham PK, et al. Premedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate. Anesth Analg. 1998;86(1):66-70.
5.  Karlsen KL, Persson E, Wennberg E, Stenqvist O. Anaesthesia, recovery and postoperative nausea and vomiting after breast surgery. A comparison between desflurane, sevoflurane and isoflurane anaesthesia. Acta Anaesthesiol Scand 2000;44(4):489-93.
6.  Tramer M, Moore A, McQuay H. Meta-analytic comparison of prophylactic antiemetic efficacy for postoperative nausea and vomiting: propofol anaesthesia vs omitting nitrous oxide vs total i.v. anaesthesia with propofol. Br J Anaesth. 1997;78(3):256-9.
7.  Tramer M, Moore A, McQuay H. Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials. Br J Anaesth. 1996;76(2):186-93.
8.  Appadu BL, Lambert DG. Interaction of i.v. anaesthetic agents with 5-HT3 receptors. Br J Anaesth. 1996;76(2):271-3.
Site Editor: Stephen B. Corn, M.D. and B. Scott Segal, M.D.
Department of Anesthesia, Harvard Medical School