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Anesthesia & Analgesia:
doi: 10.1213/ANE.0b013e318254285e
Editorials: Editorial

Postoperative Nausea and Vomiting: Then & Now

Habib, Ashraf S. MBBCh, MSc, MHSc, FRCA; Gan, Tong J. MB, MD, MHSc, FRCA

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From the Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

Funding: Departmental.

Conflicts of Interest: See Disclosures at the end of the article.

Reprints will not be available from the authors.

Address correspondence to Tong J. Gan, MB, MD, MHSc, FRCA, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to tjgan@duke.edu.

Accepted March 1, 2012

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Some Observations on the Value of Pre-Operative Treatment for the Surgical Patient in Relation to Anesthesia

W. J. DeFries, M.D., Anesthetist, Toronto, Canada

Then Postoperative vomiting has always been dreaded by the surgeon as well as the anesthetist. We all have seen patients who, even after an operation of short duration, during which time the anesthetic was administered by a skilled anesthetist, vomit persistently, while others, after long operations, the anesthetic being given by the junior interne, have recovered without even being nauseated. This would lead to the belief that certain persons are more prone to vomit than others, and so it is simply their misfortune. But investigations of this condition have come to the conclusion that nausea, vomiting, distension, gas-pains, headache and other symptoms of profound shock, which may end on death, are all symptoms of an acid intoxication, and while postoperative treatment is helpful and sometimes curative, yet preoperative treatment is very frequently prophylactic. Wm. H. Morris points out that while the administration of sodium bicarbonate increases the alkali reserve, the value of this treatment is shown postoperatively, and he claims that sodium bicarbonate given before operation is a rational precautionary measure against postoperative vomiting.1

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Postoperative Nausea and Vomiting

Ashraf S. Habib, MBBCh, MSc, MHSc, FRCA, and Tong J. Gan, MB, MD, MHSc, FRCA

Now As we read Dr. Defries comments in the first issue of Anesthesia & Analgesia in 1922, we realize that he identified several important aspects of postoperative nausea and vomiting (PONV), some of which are still being investigated. For instance, there is no doubt that PONV remains a “dreaded” complication, but the reasons might be different now than at the time this article was published. In the early days of anesthesia and surgery, the main concern was safety; vomiting and aspiration were significant causes of anesthesia-related mortality, and early articles addressing this topic focused mainly on postoperative vomiting with little or no reference to nausea. However, as anesthesia became much safer with the introduction of new drugs, techniques, monitoring devices, and improved airway management, the emphasis shifted to quality, and the unpleasant symptom of nausea started to gain more attention in addition to vomiting. Patient satisfaction became an important issue, with some studies reporting PONV as being the top concern for patients after surgery.2 Furthermore, with the continued expansion of ambulatory surgery, control of PONV became critical to ensuring patient satisfaction and comfort as well as rapid discharge from ambulatory surgical centers and avoiding unplanned admissions as a result of uncontrolled PONV.

Dr. Defries correctly pointed out that some patients have the “misfortune” of being at higher risk to develop PONV than are others. Identifying risk factors for PONV have been described in the literature since the late 1800s.3 Potential risk factors described in a review about postoperative vomiting4 published in 1934 included patient factors (excessive anxiety, history of sea sickness), surgical factors (intraperitoneal surgery, elective surgery!), and anesthetic factors (badly given anesthetic!). Interest in understanding risk factors for PONV continued, but studies were limited by focusing on a single risk factor at a time, without controlling for other potential variables. Therefore a long list of potential risk factors has been suggested over the years, with some of these subsequently disproved such as obesity5 and the stage of the menstrual cycle.6 Significant advances in our understanding of the risk factors for PONV occurred in the 1990s with the publication of prospective studies using sophisticated regression techniques to simultaneously investigate numerous risk factors. This led to the publication of scoring systems to quantify the patient's risk for developing PONV, as well as studies validating those risk factors. This is still a work in progress; scoring systems are far from perfect, and new studies are investigating genetic and molecular biology patient characteristics as well as other clinical features and patient populations that have not been well studied.

Our understanding of the pathophysiology of PONV has significantly advanced since the publication of this article in 1922. This is reflected in the strategies that have been used over the years to manage PONV. For instance, Dr. Defries pointed to acidosis as a possible etiology for postoperative vomiting, and suggested that preoperative administration of sodium bicarbonate reduces postoperative vomiting.1 With the same rationale, Potter published an article in Anesthesia & Analgesia in 1926 describing the use of a glucose insulin infusion regimen as an effective modality to prevent postoperative vomiting.7 It was also suggested that ether-induced vomiting might be due to an action on the intestine. This led to reports describing the ingestion of olive oil prior to general anesthesia or after regaining consciousness following surgery to absorb any ether that might be in the stomach and reduce the incidence of postanesthesia vomiting.8 Better understanding of the physiology of vomiting led to the description in 1939 of the chemoreceptor trigger zone in the area postrema as a site for emetogenic stimuli in the blood.9 Whereas the role of anticholinergics as antiemetics was noted as early as 1883, better understanding of the receptors involved in the etiology of PONV occurred in the 1950s and 1960s.10 This led to investigation of the antiemetic effect of drugs acting at those receptors, such as antihistamininics and antidopaminergics. Whereas the use of those nonspecific antiemetics improved the prophylaxis of PONV, their use was associated with numerous side effects. Investigation of the mode of action of high-dose metoclopramide led to the introduction of the 5HT3 receptor antagonists in practice in the 1980s. This represented a big milestone in the management of PONV, because this was the first class of drugs introduced specifically to manage chemotherapy-induced nausea and vomiting and PONV. Furthermore, the 5HT3 receptor antagonists had the advantage of a cleaner side effect profile, in particular lack of sedation that was a problem with many of the older nonspecific agents used for the management of PONV. With the concurrent increase in ambulatory surgery over this time period, the lack of sedation was a particularly desired feature because it avoided prolonged postanesthesia care unit stays associated with the use of older sedating antiemetics. When first introduced, these agents were much more expensive than older generic drugs, and this led to studies evaluating the cost effectiveness of the 5HT3 receptor antagonists in comparison with older agents as well as evaluating the merits of prophylaxis versus a wait-and-see approach in which antiemetics are used only for the treatment of established symptoms. It is interesting to note that as early as 1922, Dr. Defries commented on the value of prophylaxis versus postoperative treatment. The turn of the millenium saw the introduction of the NK1 receptor antagonists, a new class of drugs developed specifically for chemotherapy-induced nausea and vomiting and PONV management, which are free of sedative side effects, have a much longer duration of action than do other antiemetics, and seem to be particularly effective for the prophylaxis against vomiting. Numerous other strategies for reducing the risk of PONV were also introduced, such as nonpharmacological techniques, in particular, acupuncture, using the pericardial 6 (P6) acupoint.11

Now with our knowledge of the different receptor systems involved in the pathogenesis of PONV, we achieved improved prophylaxis by the adoption of a combination therapy approach using several antiemetics targeting different receptor sites, particularly in high-risk patients. With the continued expansion of ambulatory surgery, we started to focus on postdischarge nausea and vomiting and collect data for extended periods of time after surgery. The literature on PONV continued to expand at a prolific rate, and numerous review articles, meta-analyses, and consensus guidelines12 form the basis of an evidence-based approach to the management of this problem.

We have achieved significant progress in PONV management in the 90 years since the publication of Dr. Defries article. We have moved from almost an 80% incidence in the ether and chloroform era to an overall 20%–30% incidence nowadays. Once a cause of anesthesia-related mortality, PONV is almost never fatal in current practice but can rarely result in serious adverse effects in some cases. Furthermore, our patients have a strong preference for avoiding PONV, even willing to pay up to US$100 to avoid vomiting.13 We should continue our efforts to better understand the mechanism of PONV and opioid-induced nausea and vomiting in individual patients, appreciate the role of genetics, and develop more effective antiemetics with minimal side effects to achieve further progress and improve patient outcome following surgery.

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DISCLOSURES

Name: Ashraf S. Habib, MBBCh, MSc, MHSc, FRCA.

Contribution: This author helped write the manuscript.

Attestation: Ashraf S. Habib approved the final manuscript.

Conflict of interest: This author has no conflict of interest to declare.

Name: Tong J. Gan, MB, MD, MHSc, FRCA.

Contribution: This author helped write the manuscript.

Attestation: Tong J. Gan approved the final manuscript.

Conflict of interest: Tong J. Gan received research funding from Cara Therapeutics, received research funding from Premier Inc., received research funding from AcelRx., received research funding from Cheetah Medical, and received research funding from Acacia, Speaker's Bureau: Baxter, Hospira, Cadence, Fresenius-Kabi.

This manuscript was handled by: Steven L. Shafer, MD.

“The characteristic of scientific progress is our knowing that we did not know.”—Gaston Batchelard

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REFERENCES

1. DeFries WJ. Some observations on the value of pre-operative treatment for the surgical patient in relation to anesthesia. Anesth Analg 1922;1:79–82

2. Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg 1999;89:652–8

3. Blumfeld J. The prevention of sickness after anesthetics. Lancet 1899;154:833–5

4. Smith GFR. Post-operaive vomiting. Br J Anaesth 1934;11: 132–9

5. Kranke P, Apfel CC, Papenfuss T, Rauch S, Lobmann U, Rubsam B, Greim CA, Roewer N. An increased body mass index is no risk factor for postoperative nausea and vomiting. A systematic review and results of original data. Acta Anaesthesiol Scand 2001;45:160–6

6. Eberhart LH, Morin AM, Georgieff M. [The menstruation cycle in the postoperative phase. Its effect of the incidence of nausea and vomiting]. Anaesthesist 2000;49:532–5

7. Potter C. Insulin-glucose in the prevention of postanesthetic vomiting. Anesth Analg 1926;5:69–72

8. Ferguson RH. The use of olive oil to prevent or relieve postanesthetic vomiting. New York Med J 1912;95:1359–61

9. Wang SC, Borrison HL. A new concept in the organisation of the central emetic mechanisms: recent studies on the site of action of apomorphine, copper sulphate and cardiac glycosides. Gastroenterology 1952;22:1–12

10. Raeder J. History of postoperative nausea and vomiting. Int Anesthesiol Clin 2003;41:1–12

11. Lee A, Fan LT. Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2009:CD003281

12. Gan TJ, Meyer TA, Apfel CC, Chung F, Davis PJ, Habib AS, Hooper VD, Kovac AL, Kranke P, Myles P, Philip BK, Samsa G, Sessler DI, Temo J, Tramer MR, Vander Kolk C, Watcha M. Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2007;105:1615–28

13. Gan T, Sloan F, Dear Gde L, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001;92:393–400

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