Nausea, Vomiting, and Hiccups: a Review of Mechanisms and Treatment

CONTINUING EDUCATION Nausea, Vomiting, and Hiccups: A Review of Mechanisms and Treatment

Daniel E. Becker, DDS Associate Director of Education, General Dental Practice Residency, Miami Valley Hospital Dayton, Ohio

Nausea,vomiting, and hiccups are troubling complications associated with sedation and general anesthesia.This article will review the basic pathophysiology of these events and current recommendations for their prevention and management.

Key Words: Nausea; Vomiting; PONV; Hiccups; Anesthetic complications; Antiemetics.

ausea and vomiting is one of the most common expulsion of vomitus (ie, dry heaves). The term nausea N postoperative complaints from patients follow- referstoasubjectivefeelingoftheneedtovomit.The ing general anesthesia, second only to pain. Its occur- nauseated patient does not necessarily vomit or retch. rence is miserable for the patient and both troubling Nausea should be distinguished from dyspepsia (upset and perplexing to the provider. It is not surprising that stomach), which encompasses epigastric burning, a staggering number of publications have been dedi- gnawing discomfort, bloating, or pain. It is not uncom- cated to the prevention and management of this common for nausea to accompany dyspepsia, but they are plication. Unfortunately, its pathophysiology is incom- distinct events. pletely understood, and the many contributing factors Thevomitingcenterliesinthemedullaoblongata have rendered the majority of these publications in- and comprises the reticular formation and the nucleus conclusive. In many cases, this has spawned miscon- of the tractus solitarius. When activated, motor path- ceptions and anecdotes that are not scientifically waysdescendfromthiscenterandtriggervomiting. grounded.This continuing education article summariz- These efferent pathways travel within the 5th, 7th, es current thinking and guidelines on the subject and 9th, 10th, and 12th cranial nerves to the upper gastro- also addresses the issue of hiccups, a less frequent but intestinal tract, within vagal and sympathetic nerves to nevertheless troubling complication. the lower tract, and within spinal nerves to the diaphragm and abdominal muscles.1 The vomiting center can be activated directly by irritants or indirectly fol- DEFINITIONS AND PHYSIOLOGY lowing input from 4 principal areas: gastrointestinal tract, cerebral cortex and thalamus, vestibular region, Postoperative nausea and vomiting (PONV) is the con- and chemoreceptor trigger zone (CRTZ).The CRTZ is ventional title for this complication, and PONV has be- closest in proximity, lying between the medulla and come the official medical subject heading in the Na- the floor of the fourth ventricle. Unlike other brain tional Library of Medicine. However, this label should centers, it is not protected by the blood-brain barrier. not detract from the fact that nausea and vomiting are This is to say that the endothelium of its capillaries is distinct entities that may occur at any point during or not tightly joined or surrounded by glial cells and is after a clinical procedure.Vomiting or emesis, which is permeated easily by irritants regardless of their lipid the actual oral expulsion of gastrointestinal contents, solubility or molecular size. The components of this istheresultofcontractionsofthegutandthethoraco- vomiting network are illustrated in Figure 1, along with abdominal wall musculature. This contrasts with regur- principal receptors and ligands that provide activation. gitation, which is the effortless passage of gastric con- Before vomiting occurs, there may be a period of an- tents into the mouth. Retching is the term used to de- tiperistalsis, in which rhythmic contractions occur up scribe the muscular events of vomiting without the digestive tract instead of downward. This may commence as far down as the ileum, with the antiperi- Address correspondence to Dr Daniel E. Becker at debecker@ staltic wave pushing contents of the lower small intes- mvh.org. tine contents upward into the duodenum and stomach Anesth Prog 57:150^157 2010 ISSN 0003-3006/10 E 2010 by the American Dental Society of Anesthesiology SSDI 0003-3006(000) 150 Anesth Prog 57:150^157 2010 Becker 151

explanation has been offered for the increased incidence in female patients, but this increased risk per- sists throughout life, even following menopause, which obviates any role for estrogen as a factor. It is speculated that smokers may have developed some tolerance because of the chronic emetogenic influence of nico- tine, which is lacking in the nonsmoker. A history of motion sickness suggests a more susceptible vestibular component. Nevertheless, it is surprising that none of these factors is a reliable predictor independently. For example, a prior history of PONV would intuitively suggest high risk, but female gender is actually a stron- ger independent predictor.2 Thenatureandextentofthesurgicalprocedure have been studied extensively. The most commonly cited procedures and their possible mechanisms are as follows: tympanoplasty (vestibular stimulation), Figure 1. Pathophysiology of nausea and vomiting. Vomit- ing is caused by noxious stimulation of the vomiting center ENT and oral surgery (swallowed blood), breast sur- directly or indirectly via 1 or more of 4 additional sites: the gery (anxiety and emotional load), laparoscopy (peri- gastrointestinal (GI) tract, the vestibular system, the chemo- toneal irritation), and abdominal and hysterectomy receptor trigger zone, and higher centers in the cortex and (GI and vagal stimulation). With the exception of stra- thalamus. Once receptors are activated, neural pathways bismus surgery in children, no surgical procedure is a lead to the vomiting center, where emesis is initiated. Neural traffic originating in the GI tract travels along afferent fibers sound independent predictor. PONV in these cases ofcranialnervesIX(glossopharyngeal)andX(vagal).Anti- more likely reflects prolonged exposure to emetogenic emetic targets for drug interventions are predicated on their anesthetics and underlying patient-related factors.3 ability to block the illustrated receptor sites. Receptors illus- Emetogenic agents have the strongest evidence for trated along with their conventional ligands are as follows: risk of PONV. Patient and surgical risk factors likely H1 histamine, M1 acetylcholine, 5-HT3 serotonin, DA2 dopamine, NK1 (neurokinin) substance P, and mu/kappa opioids. play a role in the susceptibility to these agents. Transmitter mediators in the cerebral cortex and thalamus Opioids have well-established emetogenic effects. The are poorly understood, although cortical cannabinoid (CB1) degree of risk is predicated on the total dose adminis- pathways have been characterized. tered, not on the particular agent or whether it is administered intraoperatively or postoperatively.3 Fur- within a few minutes. Then, distention within these thermore it occurs more frequently following ambula- upper portions of the gastrointestinal tract generates tion, which suggests a vestibular component in its afferent impulses to the vomiting center, where the ac- pathogenesis. Inhalation anesthetics are also well-es- tual act of vomiting is initiated.1 For this reason, an tablished emetogenics, with the volatile agents more empty stomach does not preclude the expulsion of so than nitrous oxide.4^6 Their degree of risk is direct- vomitus. At the onset of vomiting, intrinsic contrac- ly related to duration of exposure. Propofol is com- tions occur in both the duodenum and the stomach, monly regarded as an antiemetic, but whether nonsed- the lower esophageal sphincter relaxes, and vomitus ative doses actually impart an antiemetic influence is moves from the stomach into the esophagus. Next, equivocal.7, 8 At sedative doses, however, both propo- the inspiratory and abdominal muscles contract and fol and midazolam appear to increase threshold for expel the vomitus into the mouth. postoperative nausea.9 Nevertheless, there is little doubt that propofol is far less emetogenic than the inhalation agents.4,10 FACTORS CONTRIBUTING TO PONV

PONV is multifactorial in its origin. In addition to well- ANTIEMETIC DRUGS established emetogenic agents such as opioids and inhalation anesthetics, a large number of factors appear The efficacy of antiemetic drugs is predicated on their to render patients more susceptible. Patient-related ability to act as antagonists at receptor sites within the factors with the most established significance include vomiting center and associated regions (Figure 1). female gender, nonsmoking history, anxiety and prior From an empiric standpoint, those that block acetyl- history of PONV, motion sickness, and migraine. No choline and histamine appear most useful when ves- 152 Nausea, Vomiting, and Hiccups Anesth Prog 57:150^157 2010

Ta b l e 1. Relative Actions of Selected Antiemetic Drugs*11 Dose (mg) Relative Antagonist Activity Product IV/PO Muscarinic Histaminic Dopamine Serotonin Scopolamine (1.5 mg transdermal patch) ++++ + 00 Diphenhydramine 25^50/25^50 ++ ++++ 00 Hydroxyzine NA/25^100 ++ ++++ 00 Promethazine` 12.5^25/25 ++ ++++ ++ 0 Prochlorperazine` 2.5^10/5^10 ++ ++ ++++ + Droperidol 0.625/NA 0 + ++++ + Metocloprami de 10^20/10^20 0 0 +++ ++ Ondansetron 1^4§/16 0 0 0 ++++ * Designations of 0-++++ reflect relative activity as antagonists. Actions based on low activity (+) are less likely to be achieved with conventional doses. NA indicates not available. Doses derived from Access Medicine Drug Monographs, McGraw-Hill, 2010. ` Available as 25-mg rectal suppositories. § 1mg is recommended for rescue, and 4 mg for prophylaxis. tibular triggers are suspected, and dopamine blockade gic activity within the basal ganglia. For this reason, targets the emetogenic influence of opioids in the the more specific anticholinergic actions of diphenhy- vomiting center and CRTZ. The serotonin antagonists dramine are useful for countering acute episodes.12 act not only in the vomiting center but within the GI Promethazine (Phenergan) and prochlorperazine tract, where surgical manipulation or many of the che- (Compazine) are among the most commonly used an- motherapeutic agents generate their noxious influ- tiemetics. In the emergency room setting, prometha- ence. Anxiolytic medications are useful in cases where zine was found to have a greater sedative effect, but anticipatory anxiety is high. Despite the logic of these prochlorperazine was more effective as an antiemetic drug actions, more than a thousand publications have with a similar incidence of akathisia.13,14 failed to clearly establish the superiority of a particular In addition to its antidopaminergic action, metoclo- agent, regardless of risk factors. Part of this is due to pramide (Reglan) has a prokinetic action on the upper inconsistency in study design, but it also reflects the digestive tract. By acting as an agonist at a specific extreme difficulty of factoring the many contributors subtype of serotonin receptor (5-HT4), it simulta- and causes for both nausea and vomiting. Selected an- neously increases tone in the lower esophageal tiemetic drugs and their relative activity in blocking re- sphincter and increases gastric motility, both of which ceptor sites are summarized inTable 1.11 promote gastric emptying. These actions make it an attractive antiemetic in patients with a history of gastroesophageal reflux. Dopamine Antagonists Many antiemetic and psychotropic drugs that have dopaminergic and cholinergic blocking activity have Drugs that block dopamine are effective antiemetics been implicated in producing a prolonged Q-T inter- for most causes of PONV. Unfortunately, their ability val, an electrocardiographic change that may trigger to also block dopamine transmission within the basal tachyarrhythmias such as torsades de pointe. Recent- ganglia may result in so-called extrapyramidal syn- ly, this has been a well-published concern for droperi- dromes (EPSs) that include akathisia, parkinsonian dol. However, this worry was spawned by case reports symptoms, and tardive dyskinesia. Of these syn- wherein large doses were administered in hospital dromes, akathisia is most common and presents as a emergency departments and intensive care units. This subjective feeling of restlessness leading to a compel- proarrhythmic side effect is not considered relevant at ling need to move. Patients feel that they must get up low antiemetic doses, that is, those not exceeding and walk or continuously move about. This behavior 0.625 mg.3 may be mistaken for agitation, and their distinction is critical to avoid an inclination to further sedate the patient. Although extrapyramidal symptoms are bizarre 5-HT3 (Serotonin) Blockers and generally frighten the patient and practitioner alike, they are never fatal. Like Parkinson’s disease, The 5-HT3 (serotonin) antagonists were introduced this syndrome reflects not only a defect in dopaminer- initially to combat radiation and chemotherapy-in- gic transmission, but also a relative excess of choliner- duced nausea and vomiting. This was based on pivotal Anesth Prog 57:150^157 2010 Becker 153 roles for radiation, cisplatin, and other chemothera- ing. This generally is related to obstetrical and other peutic agents in triggering serotonin release within procedures performed under neuroaxial blockade, the gastrointestinal wall. The subsequent reduction in during which vasovagal and other causes for hypoten- the cost of these antiemetics and additional under- sion are implicated in precipitating PONV. Any anti- standing of the roles of serotonin within the vomiting emetic benefit is likely secondary to preventing these center have expanded the use of 5-HT3 antagonists events. Likewise one hears mention of supplemental for PONV. Newer members of this class have not been oxygen as conferring an antiemetic influence, but this found more effective than the initial prototype, ondan- also is untrue.18 setron (Zofran). Use of these agents is particularly attractive when drugs that have antidopaminergic or anticholinergic Drugs of Choice actions are to be avoided. Dopamine blockade obvi- Results from an astounding number of clinical trials ouslyshouldbeavoidedifpossibleinpatientswith have not been able to clearly distinguish drugs of Parkinson’s disease. Severe dementias such as Alzhei- choice for specific clinical situations, especially for mer’sdiseaseareduetodegenerativechangesincorti- acute intervention. For the patient who is experiencing cal cholinergic pathways, and drugs that have signifi- nausea and vomiting during the postoperative period, cant anticholinergic actions should be avoided.15 reasonable choices are promethazine, prochlorperazine, and ondansetron. Considering its low generic Novel Agents cost and low side effect profile, ondansetron is most attractive. In terms of prophylaxis, however, results from large meta-analyses favor the use of ondanse- Drugs that block the neurokinin 1 (NK1)receptorhave proven efficacy in chemotherapy-induced nausea and tron, dexamethasone, or droperidol alone or in combi- 3,19 vomiting. They are most effective in preventing de- nation. layed nausea and generally are used in conjunction with 5-HT3 antagonists for this reason. Aprepitant (Emend) is the first of these agents to be introduced, PREDICTING AND MANAGING PONV but its efficacy for PONV is not established. Likewise, the cannabinols such as tetrahydrocannabinol found The routine use of prophylaxis for PONV is unwar- in marijuana and dronabinol (Marinol), a synthetic de- ranted. This is particularly true for moderate or deep rivative, have proven efficacy only for chemotherapy- sedation techniques using midazolam, propofol, and induced nausea and vomiting. conventional doses of opioids. However, for patients Glucocorticoids such as dexamethasone are well-es- with well-defined risks, especially when inhalation tablished antiemetics for chemotherapy-induced as agents are to be used, prophylaxis may be justified. Apfel not only has authored an impressive list of clini- wellaspostoperativenauseaandvomiting.Howthey cal studies but has performed an extensive analysis of produce this effect is unknown, but it is speculated the literature.3 His recommendation regarding risk as- that they may suppress production of inflammatory sessment and management provides an excellent autacoids that may somehow potentiate known vomit- guidelineforsedationandanesthesiaindentalprac- ing pathways within the vomiting center. A similar tice (Table 2).3,20 mechanism has been proposed to explain the benefi- cial effects of nonsteroidal anti-inflammatory drugs in nausea and vomiting induced by systemic irradiation. Management of Aspiration Glucocorticoids have a slow onset of action, and their benefit is limited to prophylactic regimens. If a patient experiences nausea, vomiting, or regurgita- Acupuncture has been fairly well established in the tion, proper management can minimize any significant prevention of PONV.16 It consists of stimulating the consequences. The nauseated patient may be more so-called P6 wrist point (located on the ventral surface comfortable in Fowler’s or semi-Fowler’s position, but of the forearm approximately 3 fingerwidths proximal if vomiting or regurgitation occurs, or appears emi- to the wrist joint) by using acupuncture, acupressure, nent, the patient should be placed in a reclined posi- and other techniques. The reader is referred to an ex- tion, with the head lower than the chest and abdomen; cellent review of principles and devices by Chernyak apartialorfullTrendelenburgispreferred.Thiswillre- and Sessler.17 duce the risk for aspiration. Also, the patient should be Occasionally one hears anecdotal evidence regard- turned on the right side based on anatomical considering the use of ephedrine to prevent nausea and vomit- ations. The right primary bronchus branches at a less 154 Nausea, Vomiting, and Hiccups Anesth Prog 57:150^157 2010

Ta b l e 2. Recommendation for Prevention and Management Hiccups of PONV*3,20 Number of Risk Hiccup (singultus) is a fairly common phenomenon Risk Factors Factors Prophylaxis Strategy that generally is only a nuisance but may become more troubling when prolonged. A hiccup consists of Female gender 0^1 None Nonsmoker 2 4 mg dexamethasone sudden contraction of the diaphragm and intercostal History of PONV 6 2nd antiemetic muscles followed immediately by laryngeal closure. Use of opioids 3^4 Avoid inhalation agents if They commence most often during inspiration and .100 mcg possible + 4mg are inhibited by elevations in PaCO2;thisservesas fentanyl or dexamethasone 6 2nd the basis for breath holding or breathing into a paper equivalent antiemetic 23,24 Rescue Strategy:Antiemeticnotusedfor bag as a common therapeutic intervention. prophylaxis, eg, ondansetron1mg IV. Aso-called‘‘bout’’ofhiccupsmaylastforadayor2, * Based on risk factors designated in this table, the inci- but episodes lasting longer than 48 hours are labeled dence of PONV following general anesthesia (including inha- as persistent, and those lasting longer than 2 months lation agents) is 0 (9%), 1 (20%), 2 (39%), 3 (60%), and 4 are regarded as intractable.25 More than 100 causes of (78%).The following information was derived from an algo- persistent or intractable hiccups have been identified, 3 rithm for management of PONV by Apfel. For intravenous including infection, trauma, tumor, and a myriad of techniques using low doses of opioids (#100 mcg fentanyl or equivalent), prophylaxis is probably unwarranted regardless gastrointestinal, metabolic, and psychogenic disor- of risk factors. ders. In contrast, brief bouts of hiccups associated with anesthesia practice are more often precipitated by anesthetic medications or gastric distention from swal- acute angle from the trachea, and aspirated material is lowing blood and debris. more likely to enter the right lung, at least initially. The hiccup reflex is not fully understood but con- Turning the patient to the right side may spare the left sists of 3 general components: an afferent limb travel- lung from aspirant.While positioning the patient, initi- ing within the phrenic and vagus nerves, a central pro- ate high-volume suctioning using a tonsil or Yankauer cessor, and an efferent limb traveling within the tip. Avoid placing the suction tip too deeply into the phrenic nerve to the diaphragm and accessory nerves oropharynx to avoid triggering further retching and to intercostal muscles.25 The central processor is least pushing vomitus farther into the obstructed airway. understood but is located somewhere between the cer- When vomiting ceases, it is essential to evaluate the vical spine and brainstem. Processing is provided by patient for possible aspiration. The patient should be several poorly defined neurotransmitters, including supported with supplemental oxygen and both lungs gamma-aminobutyric acid (GABA) and dopamine. auscultated. If any evidence of abnormal sounds such Triggers for hiccups are conventionally described as as wheezing or rhonchi is noted, or if oxygen satura- central or peripheral in origin. Central mechanisms tion by pulse oximetry is decreased despite oxygen are implicated in intractable cases and appear related supplementation, the patient should be immediately tovariouscentralnervoussystemdisorders,including transferred to an emergency department for further neoplasia.25,26 More often the origin of the triggering evaluation. If bronchospasm is suspected, manage- stimulus occurs peripherally in epigastric locations fol- ment should follow that for an asthmatic attack; a lowing gastric distention, irritation, or reflux.23^26 This bronchodilator should be administered (eg, albuterol would explain its occurrence following dental surgery, 2^4 inhalations). If the patient cannot cooperate with particularly in cases of excess swallowing of blood and this form of drug administration and the broncho- debris. A number of drugs have been implicated in spasm is severe, epinephrine 0.3 mg (a 1 : 1000 con- provoking hiccup, including certain antibiotics, anti- centration) should be administered intramuscularly for neoplastic agents, and dopamine agonists used in Par- adults, or 0.15 mg for children. Intubation of the pa- kinson’s disease.23^25 However, more familiar culprits tient should be considered only when hypoxemia re- to the dentist include the benzodiazepines, opioids, 25 mains severe (eg, SpO2 ,80), despite conventional ef- methohexital, and dexamethasone. It is difficult to forts at oxygenation. define precise mechanisms because drugs known to More extravagant treatment options such as bron- induce hiccups (eg, benzodiazepines, antidopaminer- chial lavage or administration of antibiotics and gluco- gic drugs) have also been used in their treatment. corticosteroids are dated and rarely if ever viable.21,22 Treatment for hiccups is obvious when the cause or These may be indicated in the most severe cases, but trigger is identified. The use of proton pump inhibitors they will be addressed more appropriately by the is effective targeted therapy for hiccups attributable to emergency room physician. gastroesophageal reflux disease (GERD). Metoclopra- Anesth Prog 57:150^157 2010 Becker 155 mide (Reglan) also may be used, as it promotes gastric 2. Apfel CC, Kranke P, Eberhart LH. Comparison of sur- emptying. More often, however, the cause is elusive, gical site and patient’s history with a simplified risk score for and most of the treatments are anecdotal or are based the prediction of postoperative nausea and vomiting. Anaes- on dated publications that have failed scientific scruti- thesia. 2004;59:1078^1082. 3.ApfelCC.Postoperativenauseaandvomiting.In: ny. Nevertheless, most of these remedies are innocu- Miller RD, Eriksson LI, Fleisher LA, et al, eds. Miller’s Anes- ous and will not harm the patient if attempted. They thesia. 7th ed. Philadelphia, Pa: Elsevier,Churchill Livingstone; include rapidly swallowing water or ice chips, breath 2009. 24^26 holding, and rebreathing from a paper bag. In all 4. Gupta A, StiererT, Zuckerman R, et al. Comparison of of these cases, a subsequent elevation in PaCO2 could recovery profile after ambulatory anesthesia with propofol, explain positive results when they occur. isoflurane, sevoflurane and desflurane: a systematic review. If hiccups continue for longer than an houror 2, despite Anesth Analg. 2004;98:632^641. attempts with innocuous remedies, pharmacological in- 5. Leslie K, Myles PS, Chan MT, et al. Risk factors for tervention can be considered. Many drug classes have severe postoperative nausea and vomiting in a randomized been suggested in the scientific literature, each having trial of nitrous oxide-based vs nitrous oxide-free anaesthesia. Br J Anaesth.2008;101:498^505. distinctly different actions, but none of these have un- 6. Myles PS, Leslie K, Chan MT, et al. Avoidance of ni- equivocal efficacy. Chlorpromazine is most frequently trous oxide for patients undergoing major surgery: a random- cited and is the only agent that has been tried enough to ized controlled trial. Anesthesiology.2007;107:221^231. receive U.S. Food and Drug Administration approval for 7. Gan TJ, El-Molem H, Ray J, Glass PS. Patient-con- this indication. It can be administered as a single IMor IV trolled antiemesis: a randomized, double-blind comparison dose of 25^50 mg or can be prescribed orally as 25 mg 3 of two doses of propofol versus placebo. Anesthesiology. times daily. However,other antidopaminergic agents can 19 99;90:15 64 ^1570. be used as alternatives.These include prochlorperazine, 8. Scuderi PE, D’Angelo R, Harris L, et al. Small-dose droperidol, and metoclopramide in dosages used for propofol by continuous infusion does not prevent postopera- postoperative nausea and vomiting. Additional options tive vomiting in females undergoing outpatient laparoscopy. include baclofen 5 mg 3 times daily and gabapentin Anesth Analg. 1997;84:71^75. 9. Hvarfner A, Hammas B, Thorn SE, Wattwil M. The in- 300 mg 3 times daily, but these provide a more gradual fluence of propofol on vomiting induced by apomorphine. response and are indicated for more chronic or prolonged 24,25 Anesth Analg. 1995;80:967^969. episodes. 10. Apfel CC, Kranke P, Katz MH, et al.Volatile anaesthet- Despite the many options, this author’s personal ics may be the main cause of early but not delayed postoper- recommendation is to use nonpharmacological ap- ative vomiting: a randomized controlled trial of factorial de- proaches initially, and if the episode continues or re- sign. Br J Anaesth.2002;88:659^668. appears following discharge, prescribe chlorproma- 11. Nasricha PJ. Treatment of disorders of bowel motility zine 25 mg tabs 3 times daily for 1^2 days. One alter- and water flux: antiemetics and agents used in biliary and native deserves mention. Benzonatate (Tessalon pancreatic disease. In: Brunton LL, Lazo JS, Parker KL, eds. Perles)isapprovedasanantitussiveagentbuthasan Goodman and Gilman’s The Pharmacological Basis of Thera- peutics. 11th ed. NewYork, NY: McGraw-Hill; 2006. established off-label use in hiccups. It is an ester local 12. Vinson DR, Drotts DL. Diphenhydramine for the pre- anesthetic derived from tetracaine. After absorption vention of akathisia induced by prochlorperazine: a random- and circulation to the respiratory tract, it distributes in- ized, controlled trial. Ann Emerg Med.2001;37:125^131. to the mucosa, anesthetizing vagal afferent fibers that 13. Ernst AA,Weiss SJ, Park S,Takakuwa KM, Diercks DB. contribute to both cough and hiccups. The recom- Prochlorperazine versus promethazine for uncomplicated mendeddoseis100mgPOevery4hours,nottoex- nausea and vomiting in the emergency department: a ran- ceed 600 mg each day. To avoid excessive numbness domized, double-blind clinical trial. Ann Emerg Med.2000; of the mouth and throat, the patient must be warned 36:89^94. against biting or chewing the medication before swal- 14. Drotts DL,Vinson DR. Prochlorperazine induces aka- lowing. Onset of action generally occurs within 20^ thisia in emergency patients. Ann Emerg Med.1999;34(4Pt 1):469^475. 30 minutes after administration, and improvement 15. Dierdorf SF, Walton JS. Anesthesia for patients with should follow 1 or 2 doses if this strategy is to be rare and co-existing diseases. In: Barash PG, Cullen BF, deemed effective. Stoelting RK, eds. Clinical Anesthesia. 5th ed. Philadelphia, Pa: JB Lippincott; 2006. 16. Lee A, Fan LT. Stimulation of the wrist acupuncture REFERENCES point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2009;(2):CD003281. 1. G uyton AC, Hall JE. Textbook of Medical Physiology. 17. ChernyakGV,SesslerDI.Perioperativeacupunctureand 11th ed. Philadelphia, Pa: Elsevier; 2006:823^824. related techniques. Anesthesiology. 2005;102:1031^1049. 156 Nausea, Vomiting, and Hiccups Anesth Prog 57:150^157 2010

18. Orhan-Sungur M, Kranke P, Sessler D, Apfel CC. New York, NY: Access Emergency Medicine, McGraw Hill; Does supplemental oxygen reduce postoperative nausea 2010. and vomiting? A meta-analysis of randomized controlled tri- 23. RopperAH, Samuels MA. Disorders of the autonomic als. Anesth Analg. 2008;106:1733^1738. nervous system, respiration, and swallowing. In: Ropper AH, 19. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial Samuels MA, eds. Adams & Victor’s Principles of Neurology. of six interventions for the prevention of postoperative nau- 9th ed. New York, NY: McGraw-Hill; 2009. sea and vomiting. NEnglJMed. 2004;350:2441^2451. 24. AldrichTK,Tso R.The lungs and neuromuscular dis- 20. Gan TJ, Meyer T, Apfel CC, et al. Consensus guide- eases.In:MasonRJ,MurrayJF,BroadusVC,NadelJA,eds. lines for managing postoperative nausea and vomiting. An- Murray & Nadel’s Textbook of Respiratory Medicine. 4th ed. esth Analg. 2003;97:62^71. Philadelphia, Pa: Elsevier Saunders; 2005. 21. Marik PE. Aspiration pneumonitis and aspiration 25.SmithHS.Hiccups.In:WalshD,ed.Palliative Medi- pneumonia. NEnglJMed. 2001;344:665^671. cine. Philadelphia, Pa: Elsevier Saunders; 2009. 22. Anderson E. Aspiration pneumonia and lung abscess. 26. Moretti R, Torre P. Hiccups. In: Bope ET, Rakel RE, In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Tintinalli’s Kellerman R, eds. Conn’s Current Therapy 2010.Philadel- Emergency Medicine: A Comprehensive Study Guide. 6th ed. phia, Pa: Elsevier Saunders; 2010. Anesth Prog 57:150^157 2010 Becker 157

CONTINUING EDUCATION QUESTIONS

1. Numerousdrugshavebeenimplicatedinproducing 3. Which of the following is useful for prophylaxis of PONV.Which of the following is least implicated as PONVbut offers no benefit for acute intervention? emetogenic? A. Dexamethasone A. Volatile anesthetics B. Ondansetron B. Nitrous oxide C. Prochlorperazine C. Propofol D. Droperidol D. Opioi ds 4. Nonpharmacological remedies for hiccups include breath holding and repeated swallowing of water or 2. Actions by which drugs may counteract PONV in- ice chips.The physiological explanation for this cludeblockinganyofthefollowingreceptorsEX- benefit is predicated on the fact that: CEPT: A. Dopamine A. It detracts the patient’s attention B. Serotonin (5-HT) B. Hiccups cannot occur duringthese processes C. Cholinergic C. Elevated PaCO2 inhibits the hiccup reflex D. Alpha D. Mild hypoxemia elevates the hiccup threshold