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Granisetron

Granisetron is a serotonin 5-HT₃ receptor antagonist used to treat nausea and vomiting following chemotherapy. Its main affect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors. more...

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Granisetron was invented by chemists working at the British drug company Beecham around 1988 and is expected to go generic in 2007/2008. It is produced by Roche Laboratories under the trade name Kytril®. The drug was approved in the United Kingdom in 1991 and in United States in 1994 by the FDA.

Granisetron breaks down slowly, staying in the body for a long time. One dose usually lasts 4 to 9 hours and is usually administered once or twice daily. This drug is removed from the body by the liver and kidneys.

Clinical Uses

Chemotherapy-induced nausea and vomiting
- 5-HT₃ receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenously about 30 minutes before beginning therapy.
Post-operative and post-radiation nausea and vomiting
Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis
Treatment of Cyclic vomiting syndrome although there are no formal trials to confirm efficacy.

Adverse Effects

Granisetron is a well-tolerated drug with few side effects. Headache, dizziness, and constipations are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver's cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

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Managing nausea and vomiting: current strategies - Cover Article
From Critical Care Nurse, 2/1/03 by Kitty Garrett

The topic of nausea and vomiting is all too familiar to most nurses. Nausea and vomiting are unpleasant complications or indications of many medical conditions and are adverse effects of hundreds of medications. Nausea and vomiting occur so frequently that they are almost considered "acceptable," usually referred to as "minor" and considered more of an inconvenience or a nuisance than a medical problem. This duo, however, is not only unpleasant but can be debilitating and can cause unnecessarily prolonged recovery times and increased costs. In critically ill patients, severe or protracted nausea and vomiting can lead to serious complications such as aspiration pneumonia, dehydration, malnutrition, and disruption of the surgical site. (1,2) Metabolic disturbances such as metabolic alkalosis, hyponatremia, hypochloremia, and hypokalemia may occur. Vomiting after craniotomy or any brain injury causes an increase in intracranial pressure. These complications can be life-threatening. Nausea and vomiting can also c ause patients to experience increased anxiety and dissatisfaction with the hospital experience and can contribute to future anticipatory nausea. (2) Also, the increased resources and time needed to treat a patient with nausea and vomiting can have a profound economic impact. (2)

Interest in this topic was recently renewed because of an enhanced understanding of the physiological mechanisms involved in the process of nausea and vomiting. Much has been published about nausea and vomiting as it relates to chemotherapy and postoperative nausea and vomiting, but many correlates can be drawn to critical care patients. In this article, we present current knowledge about the physiological mechanisms of nausea and vomiting and compare therapeutic agents (pharmacological and nonpharmacological) recommended for treating and preventing nausea and vomiting. Because it is now understood that most episodes of nausea and vomiting are preventable, implications for critical care nursing will focus on prevention rather than control of nausea and vomiting.

Definitions

Nausea and vomiting are basic human protective reflexes against the absorption of toxins, as well as responses to certain stimuli. (2) The terms nausea and vomiting are often used together, although each phenomenon should be assessed separately. Nausea is defined as a subjectively unpleasant wavelike sensation in the back of the throat or epigastrium associated with pallor or flushing, tachycardia, and an awareness of the urge to vomit. (1) Sweating, excess salivation, and a sensation of being cold or hot may occur. Vomiting, or emesis, is characterized by contraction of the abdominal muscles, descent of the diaphragm, and opening of the gastric cardia, resulting in forceful expulsion of stomach contents from the mouth. (1) Retching involves spasmodic contractions of the diaphragm and the muscles of the thorax and abdominal wall without expulsion of gastric contents, the so-called dry heaves. (1)

mechanisms of nausea find Vomiting

The activation of a nucleus of neurons located in the medulla oblongata, known as the vomiting center, initiates the vomiting reflex. The vomiting center can be activated directly by signals from the cerebral cortex (anticipation, fear, memory), signals from sensory organs (disturbing sights, smells, pain), or signals from the vestibular apparatus of the inner ear (motion sickness). The vomiting center can also be activated indirectly by certain stimuli that activate the chemoreceptor trigger zone [(CTZ).sup.3] (Figure 1). The CTZ is located in the highly vascular area postrema on the surface of the brain. This area lacks a true blood-brain barrier and is exposed to both blood and cerebrospinal fluid; thus, the CTZ can react directly to substances in the blood. (2) The CTZ can be activated by signals from the stomach and small intestine traveling along vagal afferent nerves or by the direct action of emetogenic compounds that are carried in the blood (anti-cancer drugs, opioids, ipecac).

Specific neurotransmitters and neuromodulators in the CTZ identify substances as potentially harmful and relay impulses to the vomiting center to initiate the vomiting cascade so that the harmful substance can be expelled. These neurotransmitters are serotonin, dopamine, acetylcholine (muscarinic cholinergic), and histamine. A fifth chemoreceptor, the neurokinin-1 neuropeptide, also called substance P, is currently under study. (4,5)

Stimulation of these chemoreceptors triggers activation of the vomiting center. Therefore, any interference with the transmission of these chemoreceptors prevents the vomiting center from being activated. Many antiemetics act by blocking 1 or more of these receptors. (3) Dopamine antagonists block dopamine receptors; muscarinic antagonists block acetylcholine receptors; histamine blockers block histamine receptors; and serotonin receptor blockers block serotonin receptors. The adverse effects of these drugs are also determined by which receptor site is blocked (3) (Table 1).

Chemotherapy-Induced nausea and Vomiting

Nausea and vomiting are among the most distressing and debilitating adverse effects of chemotherapy. Even though chemotherapeutic agents are not routinely administered in critical care, cancer patients who have had chemotherapy are often admitted to critical care areas. Hence, a discussion of nausea and vomiting would not be complete without a description of the clinical studies in this area.

Mechanism

Chemotherapeutic agents stimulate enterochromaffin cells in the gastrointestinal tract to release serotonin, which activates serotonin receptors. Activation of the receptors activates the vagal afferent pathway, which activates the vomiting center and causes an emetic response. (10) The emetic potential of a chemotherapeutic agent itself is the major stimulus for nausea and vomiting in chemotherapy-induced nausea and vomiting (CINV). (1) Chemotherapeutic agents are rated according to their emetic potential; 1 indicates the least potential, and 5 indicates the greatest. An example of an agent with the lowest emetic potential (1) is vincristine. An example of an agent with the highest emetic potential (5) is cisplatin. The American Society of Health System Pharmacists (ASHP) recommends prophylactic antiemetic therapy when drugs with antiemetic potential of levels 2 to 5 are used' (Table 2).

Risk Factors

In addition to the emetic potential of the chemotherapeutic agents, several other risk factors can be used to predict the likelihood of CINV. Patients younger than 50 years have more nausea and vomiting than do older patients. (1) Women are more susceptible than men, presumably because of the influence of hormones. (2) A history of motion sickness, pregnancy-related nausea and vomiting, or nausea and vomiting with previous chemotherapy are all positive predictors of CINV. (1) Patients who use alcohol heavily or who have done so in the past have a reduced risk of emesis. (1,11)

Patterns of nausea and Uomiting

Anticipatory nausea and vomiting occur before the beginning of a new cycle of chemotherapy, in response to conditioned stimuli such as the smells, sights, and sounds of the treatment room or the presence of a specific person designated to administer the chemotherapy. (12) Anticiatory nausea usually occurs 12 hours before administration of chemotherapy in patients who have experienced failed control of nausea and vomiting in previous treatments.

Acute nausea and vomiting occur within the first 24 hours after the administration of chemotherapy, usually within the first 1 to 2 hours. This type is initiated by stimulation primarily of dopamine and serotonin receptors in the CTZ, which triggers the vomiting cascade. (1) It resolves within 24 hours.

Delayed nausea and vomiting begin at least 24 hours after the administration of chemotherapy and may last up to 120 hours. Patients who experience acute CINV are more likely to also experience delayed emesis. (12) The causative mechanism in delayed nausea and vomiting is not well defined, but the metabolites of the chemotherapeutic agents are thought to continue to affect the central nervous system and the gastrointestinal tract. (1,13)(p546-549) For example, cisplatin causes delayed nausea and vomiting, up to 48 to 72 hours after administration, in more than half of all patients who receive the drug. (1) Other agents that cause delayed nausea and vomiting are high-dose carboplatin, cyclophosphamide, and doxorubicin.

Breakthrough nausea and vomiting occur despite preventive therapy and require additional therapy. (1) Antiemetic treatment administered to patients who have not responded to prophylactic regimens is often referred to as rescue therapy. (13)

Treatment

Prevention of Acute CINV. Antiemetic therapies have been compared in many clinical trials, especially since the advent of the relatively new class of drugs, the serotonin receptor antagonists (SRAs). Because chemotherapeutic agents initiate activation mainly of serotonin receptors, which leads to CINV, the SRAs are among the most effective drugs for prevention of CINV. These drugs have become the gold standard of antiemetic therapy, (10) and they are recommended by the ASHP as the drugs of choice in patients receiving chemotherapeutic agents with emetic potential of 3 to 5. (1) The SRAs prevent emesis by blocking the emetic response early in the emetic pathway. (10) They are given to patients before chemotherapy to prevent CINV. Because the SRAs have no effect on the histaminergic, dopaminergic, or cholinergic receptors, they can provide highly effective relief of nausea and vomiting without many of the adverse effects associated with traditional antiemetic agents. Adverse effects of the SRAs are generally mi ld to moderate and transient; headache is the most common. (10) The SRAs used most often are ondansetron (Zofran), granisetron (Kytril), and dolasetron (Anzemet). Unfortunately, their high cost may prevent some patients from benefiting from these medications (Table 3). Because SRAs are similarly effective for controlling acute nausea and vomiting, the investigators in several comparative medical trials concluded that the least expensive SRA should be used initially. (1,4,12) Also, oral SRAs are less expensive than parenteral SRAs and are as effective as the intravenous form. (1,4,10,12) Wickam (11) found that because the SRAs are not structurally identical, they may have differences in efficacy, and she recommends that if an SRA is ineffective, a second SRA should be given.

With less toxic chemotherapeutic agents, combinations of other antiemetics may be effective. Dexamethasone and prochlorperazine are recommended for chemotherapeutic agents that have mild to moderate emetic potential. (1) The combination of dexamethasone with metoclopramide, although less effective, may also be an option.

Prevention of Delayed CINV. The SRAs alone are not useful in delayed nausea and vomiting. Complete protection from vomiting occurs more often in patients who are given ondansetron plus dexamethasone. (1) Therefore, dexamethasone is the drug of choice for prevention of delayed nausea and vomiting. (1,4,9) It should be administered with SRAs before chemotherapy.

Treatment of Breakthrough CINV If a patient experiences CINV within 24 hours despite preventive antiemetic treatment, a combination of different classes of antiemetic drugs is given. This intervention is called rescue therapy. Drugs of choice for such rescue therapy include prochlorperazine, thiethylperazine, or metoclopramide with or without diphenhydramine, or lorazepam, haloperidol, or dronabinol. (1,15) Dronabinol may be indicated in refractory CINV unresponsive to other classes of drugs. Even though the SRAs may also be effective, their superiority over traditional, less expensive agents has not been determined. (1) The choice of agent should be based on patient-specific factors. (1) All patients receiving chemotherapy should have antiemetics available as needed for rescue from breakthrough nausea and vomiting. (1) If CINV persists after the breakthrough treatment, these drugs should be given on a scheduled basis rather than on an as-needed basis.

Treatment of Anticipatory CINV. Behavioral interventions are recommended for anticipatory emesis because they produce physiological relaxation, divert attention away from the conditioned stimulus and toward relaxing images, and enhance feelings of control. (1) The amnestic and anxiolytic properties of lorazepam may also help prevent anticipatory nausea and vomiting by blocking the memory of emesis associated with chemotherapy. (1,13) Lorazepam should be given the night before and the morning of chemotherapy. (13,15)

In summary, nausea and vomiting are no longer inevitable complications of chemotherapy; most patients can get complete control of these adverse effects. The drugs of choice for prevention of acute CINV are the SRAs. Recommended treatment for prevention of delayed CINV is dexamethasone. The drug of choice for anticipatory nausea and vomiting is lorazepam. Breakthrough nausea and vomiting can be treated with prochlorperazine, metoclopramide, haloperidol, or dronabinol (Table 1).

Postoperative nausea and Vomiting

The term acute postoperative nausea and vomiting is defined as any episode of nausea or vomiting that occurs within 24 hours of receiving anesthesia. Although significant progress has been made in preventing this type of nausea and vomiting, it still occurs in 20% to 30% of patients after surgery. (1,2)

mechanism

In postoperative nausea and vomiting, a wide range of stimuli contribute to the emetic response. Most anesthetic agents and opioids stimulate the vomiting center indirectly through the CTZ. Associated factors that directly stimulate the vomiting center include sensory input (visual, olfactory, and pain) and the vestibular apparatus. Nitrous oxide directly stimulates the gastrointestinal tract, which activates the vomiting center. (2)

Causes

Preoperative Factors. The occurrence of postoperative nausea and vomiting is influenced by several factors. (1,2,16) The risk is higher in adults than in children, in women than in men, and in patients with a history of motion sickness or previous postoperative nausea and vomiting. (1) The prevalence is also greater in obese patients and in patients with delayed gastric emptying disorders such as gastroesophageal reflux disease, gastrointestinal obstruction, chronic cholecystitis, and neuromuscular disorders. (1) A history of smoking is associated with a decrease in the likelihood of postoperative nausea and vomiting. (16) Patients' characteristics have a cumulative effect in influencing the prevalence of postoperative nausea and vomiting.

Intraoperative Factors. The type of surgical procedure can also influence the occurrence of postoperative nausea and vomiting. The rate is high in patients undergoing laparoscopic procedures related to abdominal distention because of the carbon dioxide used for visualization. (1,2) The prevalence of postoperative nausea and vomiting is also greater after plastic, ophthalmic, orthopedic shoulder, gynecologic, and ear, nose, and throat surgeries than after other procedures. (1,2) Intubation itself can evoke nausea and vomiting. Longer procedures with general anesthesia are associated with more nausea and vomiting than are shorter procedures. (1,2) The type of anesthetic used is also a factor. General anesthetics vary in their propensity to cause postoperative nausea and vomiting. Etomidate, ketamine, nitrous oxide, and inhaled agents increase the risk of nausea and vomiting. (1,2) Gastric distention caused by suction or vigorous positive pressure ventilation via face mask may also increase the risk of postopera tive nausea and vomiting. (1,2) Some medications used in association with anesthesia decrease the risk of postoperative nausea and vomiting. These include atropine, which has a vagolytic effect, and propofol (Diprivan). (1) Although the exact mechanism of the antiemetic effect of propofol is not clear, the drug may have a weak serotonin antagonistic effect. (9)

Postoperative Factors. During the postoperative period, the 2 most common causes of nausea and vomiting are unrelieved pain (especially visceral or pelvic) and the opioids prescribed to control the pain. Adequate pain relief reduces the occurrence of nausea by 80%. (2) Opioids stimulate nausea and vomiting by a direct action on the CTZ. (2) Unrelieved pain directly stimulates the vomiting center (Figure 1). Nausea can also be precipitated by sudden motion, changes in body position, premature oral intake, and hypotension. (1,2)

Prevention

If postoperative nausea and vomiting can be predicted, then they should be preventable. However, prevention is sometimes difficult because of the wide range of stimuli that contribute to the emetic response. Also, many of the pathways involved in the control of postoperative nausea and vomiting are complex and are not fully understood. The decision to provide antiemetic therapy should be based on a patient's risk factors and potential for serious sequelae from vomiting. All patients at high risk should receive prophylactic antiemetics, preferably a combined regimen. (9) Evidence is conflicting on whether all surgical patients should receive routine prophylactic antiemetics. (1,2)

Selection of an antiemetic should be based on safety and efficacy, the patient's risk factors, the patient's satisfaction, and cost. No single antiemetic is superior in every situation. For the prevention of postoperative nausea and vomiting, the ASHP guidelines recommend administration of droperidol (Inapsine) or an SRA. (1) Droperidol, a dopamine receptor antagonist, is cost-effective and produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. However, since the ASHP guidelines were published, studies have indicated that droperidol can cause a prolonged QT interval, which can lead to potentially fatal cardiac dysrhythmias. The Food and Drug Administration now requires a black-box warning, and therefore droperidol is no longer considered a first-line agent in postoperative nausea and vomiting. (7) Ondansetron (Zofran) and dolasetron (Anzemet) are commonly used SRAs. Although granisetron (Kyt ril) prevents postoperative nausea and vomiting, it is not currently approved for this purpose. The cost of using SRAs is thought to be justified by patients' satisfaction in avoiding postoperative nausea and vomiting. Dolasetron or ondansetron can be given preoperatively or intraoperatively as a single dose. Combination

drugs (eg, dolasetron plus dexamethasone) increase efficacy, especially in high-risk patients. Administration of intravenous dexamethasone before induction of anesthesia prevents postoperative nausea and vomiting. (9)

The use of supplemental oxygen has been shown to decrease the occurrence of postoperative nausea and vomiting. (17) Also, the restriction of oral intake until the return of bowel function after surgery has been used for decades to decrease the occurrence of postoperative nausea and vomiting. Alternative antiemetic drugs include metoclopramide, chlorpromazine, prochlorperazine and promethazine.

Treatment

For established postoperative nausea and vomiting, the choices of antiemetic are almost identical to those used to prevent this type of nausea and vomiting, with a slight difference in some of the dosages. The SRAs are considered first-line agents, and the same alternative drugs are recommended as those used to prevent postoperative nausea and vomiting. Dopamine antagonists, because they are inexpensive, are often used.

Unlike other sedatives used also for nausea and vomiting, propofol is currently indicated only for sedation. Because it has antiemetic properties, several studies have been done to evaluate subhypnotic doses in the treatment of postoperative nausea and vomiting. Those studies had conflicting outcomes. Fujii et al (18) found that a small dose (0.5 mg/kg) was an effective antiemetic compared with droperidol and metoclopramide. Gan et al (19) concluded that patient-controlled delivery of propofol decreased the prevalence of postoperative nausea and vomiting compared with placebo. Other studies (20,21) in which propofol was used postoperatively indicated that propofol did not decrease the prevalence of postoperative nausea and vomiting.

Pain medication should not be withheld because of its potential to cause nausea and vomiting. (2) In patients who do not respond to initial therapy with 1 antiemetic agent, an agent from another pharmacological class should be added, the dose of the antiemetic should be increased to the maximum accepted range, or a combination of both approaches should be used. (1) In patients sensitive to opioids, nonopioid analgesics such as ketorolac (Toradol) can be used as an alternative to control postoperative pain. (2) Ketorolac is a nonsteroidal anti-inflammatory drug and may cause gastrointestinal irritation and toxic effects on the kidneys.

In summary, the SRAs are recommended as first-line agents in the prevention and treatment of postoperative nausea and vomiting. Administration of antiemetic medications is generally considered safe, despite an occasional adverse reaction.

Other Causes of nausea

Many medications, medical conditions, and procedures can induce nausea and vomiting. Table 4 lists the causes most common in critical care.

Drugs that cause gastric irritation (eg, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and antibiotics) can cause nausea. Examples of drugs that stimulate the vomiting center indirectly through the CTZ are digoxin, morphine, alcohol, ipecac, and anticancer drugs. Motion sickness and inner ear disorders cause nausea by directly stimulating the vomiting center. Nausea can also be induced by olfactory, visual, vestibular, and psychogenic stimuli (2) (Figure 1).

Opioids directly stimulate serotonin and dopamine receptors in the CTZ, which in turn stimulate the vomiting center. The analgesic effect of opioids is mediated by the activation of both [[mu].sub.1] and [[mu].sub.2] receptors. Activation of the [[mu].sub.2] receptor unfortunately accounts for delayed transit time through the gastrointestinal tract, which contributes to nausea and vomiting. Currently, no opioid agonists can selectively activate specific [mu] receptors, and therefore nausea and vomiting remain adverse effects of opioid therapy. (6) Tolerance to this opioid-induced nausea and vomiting usually occurs within days to weeks. (6) Although the SRAs do relieve opioid-induced nausea, they are not considered first-line drugs in long-term therapy because of their cost. Less expensive drugs such as phenothiazines, butyrophenones, anticholinergics, and motility agents are recommended. (21) In the acute short-term, however, SRAs may be used as first-line agents for opioidinduced nausea and vomit ing.

Pharmacological management

The goal of pharmacological interventions is to prevent or minimize nausea and/or vomiting. Antiemetic agents are more effective at preventing emesis than at suppressing it. (1,3) For prevention, antiemetics can be administered orally or parenterally. (3) For suppression of ongoing emesis, oral therapy is ineffective; parenteral administration is required. Parenteral therapy includes intravenous, intramuscular, and rectal routes of administration. Nausea is a complex response. No single pharmacological agent is available that blocks all the receptors that trigger nausea or elicit vomiting. Also, adverse effects may limit the use of certain antiemetics. Therefore, the choice of drugs should be individualized to each patient's needs. Combination antiemetic therapy using agents with different mechanisms of action may be necessary. (1)

Antiemetic therapies have been compared in multiple clinical trials. On the basis of the results, clinical practice guidelines for the prophylaxis and treatment of nausea and vomiting have been developed. These guidelines continue to be refined as more research is completed. Table 1 summarizes current pharmacological recommendations, emphasizing those from the ASHP, (1) the American Society of Clinical Oncology, (4) and the Mayo Clinic. (8) Table 3 provides a cost comparison of antiemetic agents.

The pharmacological recommendations presented in this article are intended for adults and not for children. Specifically, the dopamine antagonists such as prochlorperazine and metoclopramide should not be used in children. Data are insufficient to support the use of metoclopramide in children except to facilitate small-bowel intubation in endoscopic procedures. Children are more prone than adults to extrapyrimidal reactions or paradoxical reactions of restlessness and excitement when given prochlorperazine. (1)

nonpharmacoloqical management Dietary management

The traditional dietary approach to postoperative management is to provide nothing by mouth and to use a nasogastric tube for gastric decompression to prevent nausea. Once bowel sounds resume, the tube is removed, a clear liquid diet is introduced, and the diet is gradually advanced as tolerated. Although this approach is commonly practiced, use of this regimen is not supported by published reports. Jeffrey et al (22) challenged this traditional approach; they found no difference in postoperative nausea and vomiting in patients receiving a clear liquid diet compared with patients receiving a regular diet as the first postoperative meal. Other dietary modes of decreasing nausea are eating bland foods such as dry toast or crackers and drinking carbonated beverages such as ginger ale. (2)

Alternative/Complementary and Behavioral Therapy

Although medications are the first-line treatment for nausea and vomiting, the use of alternative or complementary measures as adjuncts may improve patients' outcomes and help reduce costs.

Acupressure/Acupuncture.

Acupressure originated in China. It is based on the principle of qi or chi, the energy present in living organisms. When the flow of qi is stagnant, the physical condition is affected. The application of pressure to specific points on the body unblocks abnormal energy flow and relieves signs and symptoms. The 2 points that are effective in lessening nausea and vomiting are P6 and ST36 (Figure 2). Firm and steady pressure applied to these points with the fingers lessens the intensity of chemotherapy-induced nausea. (23) Grealish et a1 (24) reported that a 10-minute foot massage was effective in decreasing the intensity of pain and nausea and improving relaxation among cancer patients.

Acupuncture also decreases nausea and vomiting; it is based on the same principles as acupressure. (25) Because acupuncture requires trained and certified personnel, it may not be a cost-effective method of treatment. However, Medicare, Medicaid, and some third-party payers now cover acupuncture fees. A list of certified acupuncturists can be found by visiting the Web site of the American Academy of Medical Acupuncture at www.medicalacupuncture.org or that of the National Acupuncture and Oriental Medicine Alliance at www.acupuncturealliance.org.

Transcutaneous Electrical Nerve Stimulation. Recently, a wristband-type device for transcutaneous electrical nerve stimulation, the ReliefBand, was approved by the Food and Drug Administration as an over-the-counter device. It is also based on the principles of acupressure and is applied at the P6 acupressure point. Use of the ReliefBand has provided significant relief from nausea and vomiting among cancer patients. (26,27)

Relaxation. In relaxation training, patients are instructed to relax muscles in order to decrease the tension of the muscles. Patients should be encouraged to take slow deep breaths; the attention to breathing serves as a distraction. In postoperative nausea and vomiting, this technique also helps the body rid itself of any residual anesthetic agent. (2) Imagery training involves using mental processes that in crease relaxation, such as recalling pleasant memories and imaging positive thoughts. Relaxation and imagery can be used together or separately. Therapeutic touch can also be used as a comfort measure. (2) These techniques are effective for treating nausea and vomiting, pain, and insomnia. (28)

Music. Ezzone et al (28) concluded that music has a beneficial effect on nausea and vomiting. Music decreases the intensity of nausea and vomiting among cancer patients, when it is used with pharmacological antiemetic treatment.

Herbs. The use of herbs to treat nausea and vomiting is controversial. In one study, (2) ginger root was more effective than placebo for treatment of postoperative nausea and vomiting. However, Ernest and Pittler (30) reviewed 6 studies on the effect of ginger to treat nausea and vomiting and concluded that ginger may or may not be effective for postoperative nausea; ginger did appear to reduce the occurrence of nausea related to seasickness, morning sickness, and chemotherapy. Dried ginger in capsules has been used to treat car sickness in animals.

Aromatherapy. The use of aromatherapy is also controversial because its scientific effectiveness and safety have not been established. Tate (31) studied the use of peppermint oil for postoperative nausea. Peppermint oil with a relatively high content of menthol was smelled by an experimental group of patients who underwent gynecologic surgery. Although the results were not statistically significant, the experimental group had a lower prevalence and/or intensity of nausea after surgery, less requirement for antiemetics, and more tolerance to analgesia, which usually causes nausea, than the control group did.

Abdominal Implant. The Food and Drug Administration recently granted humanitarian device exemption approval for an implantable system (Enterra, Medtronic Inc, Minneapolis, Minn) for the treatment of chronic, intractable nausea and vomiting due to gastroparesis of diabetic or idiopathic origin. The device consists of 2 leads with electrodes that are implanted in the antrum of the stomach and connected to a pulse generator that is surgically placed in the lower part of the abdomen. The system is programmed to deliver low-frequency, low-amplitude electrical pulses continuously to the stomach muscle. Although the exact mechanism for the suppression of nausea is not known, it is thought that the effect is due to the neurostimulation of central vagal afferent nerve pathways, not by enhanced gastric emptying as previously thought (W. L. Starkebaum, Medtronic, Inc, oral communication, November 7, 2001). The device is externally programmed in a fashion similar to that used with cardiac pacemakers. (32)

Implications for Critical Care nursing

Critical care nurses are responsible for assessing the causes of nausea and vomiting, ad ministering appropriate antiemetic agents, evaluating the effects of the agents, and providing information to physicians when changes in treatment are indicated. Antiemetic agents are most useful when given prophylactically; it is much easier to prevent signs and symptoms than to control them. Identification of patients at high risk for nausea and vomiting allows earlier intervention in the prophylaxis for and therefore the control of these effects. Even though anesthesiologists routinely screen patients preoperatively to determine which are high-risk patients, this information must be communicated to the critical care nurses caring for the patients in order to optimize patients' care. It maybe helpful to know, for example, that patients with a history of motion sickness may be more susceptible to movement-induced postoperative nausea and vomiting. (2) Care can then be taken to ensure slow and smooth movements in transfer ring and turning a patient who has such a history. Consideration should be given to administering antiemetics on a scheduled basis, rather than as needed, for patients at high risk for postoperative nausea and vomiting. (2)

Causes and Assessment

Patients should be assessed for pain, including postoperative pain, and should be treated promptly to prevent associated nausea and vomiting. Suspected opioid-induced nausea may be evaluated by determining the temporal relationship between the time the opioid was given and the onset of nausea. (6) A careful systems assessment should be done, with all possible causes investigated before nausea and vomiting are automatically labeled as opioid induced. (6)

The cardiovascular system should be assessed for hypotension due to hemodynamic compromise. Nausea may be the first symptom of hypotension. Hemodynamic sources (increased or decreased heart rate, decreased preload, increased after-load, or decreased contractility) should be investigated. Postoperatively, hypotension may be due to the restriction of fluids preoperatively, intraoperative blood loss, and the use of anesthetics, analgesics, and sedatives. (2) Vagal maneuvers caused by retching and vomiting, as occur in inferior myocardial infarction, can cause bradycardia. Myocardial oxygen demand may be increased in a patient with acute coronary syndrome exacerbated by nausea and vomiting.

The pulmonary system should be assessed for indications of pulmonary aspiration, especially in patients receiving tube feedings. Nosocomial pneumonia can be caused by aspiration of oropharyngeal secretions or gastric contents into the lungs. Preventive measures such as elevating the head of the bed, ensuring that bowel sounds are present, and routinely checking residual feeding volumes may help prevent pulmonary aspiration.

The gastrointestinal system should be assessed for abdominal distention, organomegaly, and presence of bowel sounds. Signs of hypomotility may suggest an increased risk for nausea and vomiting. Postprandial nausea and vomiting associated with bloating and satiety suggest a gastrointestinal cause. (6) Nausea and vomiting can be indications of as well as complications of acute pancreatitis.

Nausea that occurs primarily with movement can be assumed to be generated by impulses from the vestibular center. (6) Because strong odors can cause or exacerbate nausea and vomiting, especially postoperatively, exposure to odors from nearby food, strong perfume, and cleaning solutions should be minimized. (2)

Vomiting can also cause dehydration, leading to fluid and electrolyte imbalance. Fluid and electrolyte levels must be assessed and the fluids and electrolytes replaced accordingly. Nausea, headache, and oliguria are common indications of hyponatremia, which can cause cerebral edema and death if untreated. Hypercalcemia can cause nausea and vomiting. Hypokalemia and life-threatening dysrhythmias can result from loss of electrolytes due to vomiting.

Neurological causes should also be considered. Increased intracranial pressure can cause refractory nausea, and some brain tumors cause vomiting without nausea. Nausea and vomiting cause an increase in intracranial pressure and can be life threatening in a patient with brain injury. Vomiting must be avoided in patients with suspected aneurysms in order to prevent subarachnoid hemorrhage. In patients with spinal cord trauma, the movements associated with vomiting can cause further injury to the spinal cord. Nausea and vomiting occur frequently after craniotomy. Antiemetic therapy may cause sedation, making postoperative neurological assessment difficult.

Disruption of the surgical site during vomiting can cause excess bleeding, a possible need for return to surgery, increased morbidity, increased scarring, and prolonged recovery time. Such disruption can be especially dangerous after eye, neck, or facial surgery. The explosive pressure generated during vomiting can dislodge indwelling tubes or wires, particularly those that are strategically placed, such as drains used to diminish intracranial pressure, cardiac pacing wires, and chest tubes.

Medications should be evaluated for their emetogenic potential. Common offenders are chemotherapeutic agents, opioids, nonsteroidal anti-inflammatory drugs, antibiotics, and selective serotonin reuptake inhibitors. Assessment of nausea and vomiting should include determination of the severity, duration, and number of episodes. A visual analog scale can be used to measure the severity of nausea, with a scale of 1 to 10, similar to that used as a pain scale. (1,20)

Prevention and Treatment

The prevention and treatment of nausea and vomiting will become even more of a healthcare concern as hospitals are required to make the most efficient use of available resources, decrease the frequency of complications, and decrease patients' lengths of stay. (1) Traditional, convenient, cost-effective approaches to the prevention and treatment of nausea and vomiting in the intensive care unit include the use of nasogastric tubes for gastric decompression and the use of phenothiazines or metoclopramide as antiemetics. This regimen may still be effective for most patients. However, the lack of efficacy and the adverse effects (sedation, hypotension) of these drugs may limit their use. The most recently published Mayo Clinic guidelines no longer recommend metoclopramide because of the increased occurrence of restlessness, agitation, insomnia, and drowsiness associated with use of this drug. (4) Also, patients may not respond to the initially prescribed therapy. If no response occurs, then an agent from another pharmacological class should be added, the dose of the antiemetic should be increased to the maximum within an acceptable range, or both. (1,9) This adjustment may require expansion of the use of serotonin receptor antagonists in critical care.

Published views are conflicting about how much patients' satisfaction should influence the choice of agent and override the cost concerns. If a drug is more expensive but it prevents complications and decreases length of stay, it would seem to be worth the extra cost in the final analysis. More studies on the economics are needed to help weigh the cost-benefit issue.

Understanding the pathophysiology of nausea and vomiting will allow critical care nurses to assist in making appropriate decisions to prevent and treat these responses. Nonpharmacological methods should be considered as complementary therapy. Complete control, defined as no nausea or vomiting, should be the goal for every patient.

C E This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives:

1. Discuss the mechanisms of nausea and vomiting

2. Identify preoperative and postoperative factors that influence the development of nausea and vomiting

3. Describe treatment options for nausea and vomiting

Acknowledgments

Parts of this article were previously published as a synopsis in the Oncology Nursing Society Critical Care Special Interest Group Newsletter. Vol 10, Issue 2, August 2001.

We thank Dr Cynthia Chernecky, our faculty and mentor, for her inspiration, guidance, and support in writing this article. We appreciate the comments of our manuscript reviewers, as well as suggestions from Dr Mark Stewart, anesthesiologist, Dr Sandra Counts and Michael Madden, clinical pharmacists, and Dr Cyntlsia Chernecky, professor and oncology clinician. We also thank Shogo Tsuruta for his expert computer skills in compiling our pharmacology table.

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