Who among us has not heard these dreaded words, or something similar? We do our best to avoid the problem, but still we occasionally fail, hand over emesis basins, and watch unfortunate patients heave into them. Perioperative nausea and vomiting (n/v) is both feared and loathed, and is a significant detractor to patient experience and anesthesia-related quality metrics. Further, in certain types of surgery, such as intracranial, facial plastics, and intranasal ENT procedures, the physical act of emesis poses a risk for incisional dehiscence(s), bleeding, and similar morbidity.

Let’s turn to our expert this month, Dr. T.J. Gan, a physician-scientist who is well versed in the epidemiology and treatment of all things nausea and vomiting-related. He will provide a refresher and some clinical guidance; hopefully, his experience can assist us in our quest to reduce “n/v” rates to as close to zero as possible.

Dr. Gan, thank you for joining us. Can you describe your current position and responsibilities?

I am currently Professor and Head of the Division of Anesthesiology and Perioperative Medicine, Critical Care and Pain Medicine at University of Texas MD Anderson Cancer Center, a division with over 400 faculty, CRNAs, and staff.

Let’s dive right into this month’s topic. What are the most important patient risk factors for nausea and vomiting? Also, which surgical procedures are most closely associated with it?

The main risk factors for postoperative nausea and vomiting (PONV) include female gender, history of PONV and/or motion sickness, use of opioids, and nonsmoking status. Some surgical procedures, e.g., breast, laparoscopic, middle ear, strabismus repair, and neurosurgical are notably associated with higher risk for PONV.

Do we have a physiologic and/or molecular understanding of the genesis of PONV?

The act of vomiting is controlled by the vomiting center, which is located in the lateral reticular formation of the medulla. It receives input from the higher cortical centers, chemoreceptor trigger zone (CTZ), vestibular apparatus, cerebellum, and solitary tract nucleus. It also receives afferents from the optic, olfactory, vagal, glossopharyngeal, and trigeminal nerves, as well as from somatic structures such as the gastrointestinal tract, testis, pharynx, and heart. Efferent output from the vomiting center goes to the vagus, phrenic, and spinal nerves of the abdominal muscles. Receptors implicated in the etiology of nausea and vomiting include dopaminergic (D2), cholinergic (muscarinic), histaminergic (H1), serotonergic (5HT3), and neurokinin (NK-1). Currently available antiemetics act by blocking one or more of these five receptors.

What are the most efficacious treatments available in the United States?

Most approved antiemetics have similar efficacies, reducing the risk of PONV by about 25%. As PONV is multifactorial, a multimodal approach has been shown to improve efficacy. Adding the second antiemetic from a different class further reduces the incidence of PONV by another 25%. In the most recent consensus guidelines, we recommend administering at least two prophylactic antiemetics for those who have one or two risk factors and three to four for those above two risk factors (see algorithm). Commonly used antiemetics for adults are shown in Table 1, and for children are shown in Table 2.

Table 1: Antiemetic Doses for Prevention of PONV in Adults

Table 1: Antiemetic Doses for Prevention of PONV in Adults

Table 2: Antiemetic Doses for Prophylaxis of POV/PONV in Children

Table 2: Antiemetic Doses for Prophylaxis of POV/PONV in Children

For patients who develop PONV in the PACU or beyond discharge, prompt treatment is advised with an antiemetic that has not already been used.

Are there other useful treatments available worldwide that we might see here one day?

Recently, amisulpride (BARHEMSYS), a new dopamine antagonist, has been shown to be effective for prophylaxis (5 mg) and treatment (10 mg) of PONV. A new intravenous formulation of aprepitant (APONVIE) was recently approved by the FDA and can be injected as a bolus dose in the perioperative period. Oral aprepitant has been the only approved NK-1 receptor antagonist.

Can you describe any nonpharmacologic, yet efficacious, treatments?

Acupuncture is an effective nonpharmacologic technique for preventing PONV, with particular interest in the ‘P6 acupuncture point’ that lies 2 inches proximal to the wrist crease and between the tendons of palmaris longus and flexor carpi radialis. An updated Cochrane database review of over 50 random controlled trials found that P6 acupoint stimulation is well tolerated and is effective in the treatment of PONV, reducing the risks of nausea, vomiting, and the need for rescue antiemetics by similar magnitudes (RR 0.71, 95% CI 0.61-0.83; RR 0.70, 95% CI 0.59-0.83; RR 0.69, 95% CI 0.57-0.83, respectively).

What is a reasonable goal for rates of PONV?

Ideally zero, since, from the patient’s perspective, PONV is the most undesirable adverse event following surgery. It is one of the main reasons for patient dissatisfaction following anesthesia and surgery. With careful evaluation of risk factors and a comprehensive management strategy, a near zero incidence can be achieved.

Any comment on droperidol, a medication I used decades ago as a trainee, now not currently in widespread use due to the FDA’s black box warning?

In November 2001, the FDA issued a new black box warning on droperidol, which is the most serious warning for an FDA-approved drug. The FDA noted that its use has been associated with QTc segment prolongation and/or torsade de pointes, and, in some cases, fatal cardiac arrhythmias. Consequently, the FDA cautioned that droperidol should only be used when other “first-line” drugs fail. However, this decision has been challenged by many anesthesiologists. The manufacturer (Janssen-Cilag, Ltd.) decided to withdraw all formulations of droperidol. The rationale in halting production of the parenteral formulation of droperidol was solely economic. The manufacturer predicted that intravenous droperidol use would decline to such a low level following the new warning that it would be unprofitable to continue production of the parenteral formulation. Nevertheless, recently there has been some availability of droperidol on the market, and many practitioners use a smaller dose, 0.625 mg-1.25 mg.

What is your prophylactic approach to PONV?

In patients with one or two risk factors for PONV, I routinely administer dexamethasone and ondansetron as prophylactic agents. For patients with three or four risk factors, I will add either aprepitant or transdermal scopolamine. In addition, I would administer TIVA with propofol as the main anesthetic, avoiding volatile agents and nitrous oxide and use sugammadex for neuromuscular reversal instead of neostigmine. I will also minimize the use of opioids, as they are highly emetogenic, by using a multimodal analgesic regimen or regional anesthesia. Figure 1 represents a PONV management strategy algorithm for adults.

Algorithm for PONV management and summary of recommendations for PONV management in adults, including risk identification, stratified prophylaxis, and treatment of established PONV. Note that two antiemetics are now recommended for PONV prophylaxis in patients with one or two risk factors.

Algorithm for PONV management and summary of recommendations for PONV management in adults, including risk identification, stratified prophylaxis, and treatment of established PONV. Note that two antiemetics are now recommended for PONV prophylaxis in patients with one or two risk factors.

You mentioned scopolamine. Can you comment on its efficacy in patients lacking a history of motion sickness and its effects in geriatric populations?

Scopolamine has similar efficacy as the other antiemetics. It is commonly used for motion sickness but is also independently effective in the prevention of PONV. Due to the transdermal delivery, plasma concentration peaks at around four hours after administration. Hence, it should be applied in the preoperative phase. However, it is associated with a number of anticholinergic side effects, with dry mouth, double vision, and dizziness being the most prominent, especially in the elderly population. Unfortunately, the patch formulation does not allow for dose adjustment. I instruct patients to remove the patch when they are not able to tolerate the side effects.

What to do when “we’ve tried everything” and the PACU nurse calls about a patient who is still nauseated/vomiting?

If patients develop PONV in the PACU, I administer amisulpride (dopamine antagonist), diphendydramine (histamine antagonist), or promethazine (dopamine/muscarinic/histamine antagonists). Dosing of propofol in small (20 mg) boluses has been shown to be effective in quickly alleviating the severe nausea sensation. I.V. aprepitant is recommended for those who still have vomiting.

Any parting words of wisdom for our readers?

You can make a difference! PONV is an unpleasant and unfortunately common side effect of anesthesia and surgery. It is the main driver for patient dissatisfaction. With careful evaluation and planning, and appropriate use of prophylactic pharmacologic and nonpharmacologic options, patients do not have to experience this, and they will be forever grateful if you are the anesthesiologist who makes that difference.