Antiemetics




Abstract


Postoperative nausea and vomiting are a common postoperative challenge. Precipitating factors and prophylactic measures have changed repeatedly in the last decade in light of new evidence. New pharmacologic agents have been developed, while older ones are being reviewed in terms of their safety and efficacy. This chapter is an evidence-based approach to this area of practice.




Keywords

antiemetic, complication, day case, perioperative, vomiting

 




Case Synopsis


A 30-year-old female patient was scheduled for hysteroscopy as a day-case procedure. She has no past medical history of relevance. Metoclopramide 10 mg and ondansetron 4 mg were administered followed by propofol/fentanyl via intravenous induction and sevoflurane for maintenance of anesthesia. Postoperatively she had intractable vomiting that delayed her discharge from the postanesthesia care unit and was only controlled through the use of a combination of around-the-clock antiemetics for the following 48 hours, resulting in unplanned hospital admission.




Problem Analysis


Definition


One in three patients suffers postoperative nausea and vomiting (PONV). The incidence is higher for certain procedures (45% of gynecologic procedures and 80% in high-risk groups). PONV is rated by most surgical patients as the worst aspect of their perioperative experience (pain was second on the list). In the era of day-case surgery, the logistic and financial implications of unplanned overnight stay/readmission caused by severe PONV can be significant. Approaches to prophylactic and therapeutic measures are both inconsistent and of varying effectiveness.


Recognition


Nonanesthetic factors, such as mechanical bowel obstruction, pharmacologic agents, and increased intracranial pressure, can cause nausea and/or vomiting in the perioperative period. These factors should be considered independently as their pathophysiology and therapeutic approach are different.


Prevention and control of PONV has both prophylactic and therapeutic aspects and entails pharmacologic and nonpharmacologic measures. Almost all antiemetics are receptor agonists/antagonists that act centrally (and peripherally in case of metoclopramide).


Understanding their mechanism of action is crucial to appreciating the repertoire of their side effects.


Risk Assessment


Recent literature review has changed the perception of “traditional” risk factors for PONV.


Patient-Related Factors


Strong association exists between the patient age group (<50 years, >3 years) and PONV. There is sufficient evidence to indicate that female sex and history of PONV are considerable risk factors. The risk is reduced in smokers.


Historically, a number of factors were perceived to be significant contributors to the risk of PONV. Recent literature reviews have shed doubt on them, such as American Society of Anesthesiologists physical status, duration of perioperative fasting, use of nasogastric tube, early enteral intake/duration of fasting, anxiety, migraine, body mass index, and menstrual cycle phase.


Surgical Factors


Abdominopelvic surgery is associated with a significant risk of PONV (cholecystectomy, gynecologic and laparoscopic procedures).


In pediatric patients, strabismus surgery is associated with the highest risk, as well as procedures lasting more than 30 minutes. There is limited or no evidence for other procedures as independent risk factors.


Anesthesia-Related Factors


Strong association exists between general anesthesia (and its duration and depth) and PONV. Volatile agents, opioids, and nitrous oxide were identified early in anesthetic practice as offending agents. Despite the general perception, the level of experience of the anesthetist and the use of neuromuscular reversal agents are not associated with PONV.




Management


Considering the range of side effects of antiemetics (from headache to case records of torsade de pointes) and the consequences of PONV (poor patient satisfaction, unplanned admissions, and medical complications), a tailored plan of management after deploying an objective risk assessment system is highly recommended.


General Measures to Decrease Baseline Risk of PONV


Early identification of high-risk patients is mandatory. Different health systems have adopted scoring methods to ratify the risk of PONV.


Avoidance of general anesthesia (GA) and the established offending agents is a practical prophylactic approach. Total intravenous anesthesia is a sensible choice in patients with a history of severe PONV. If GA is a must, propofol offers advantages as an induction agent. The use of nitrous oxide is slowly declining, especially with a greater percentage of procedures performed as day-case surgery where PONV can significantly complicate a patient’s care. Opioid-sparing techniques using other modes of analgesia are becoming standard practice. Examples include regional techniques, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, and medications classically used for treatment of neuropathic pain. Good hydration and prompt treatment of hypotension are not only good standards of care; both can significantly reduce the risk of PONV. The debate is still ongoing regarding the routine use of prophylactic antiemetics. The implications for the patients and the health system have to be balanced against the incidence of side effects and the feasibility/affordability. The evidence for prophylactic agents is that efficacy is similar among the commonly used agents, and combination therapy is more effective than single-agent therapy.


Interventional Measures


Although low-risk patients may not require any measures beyond those listed previously, high-risk patients would benefit from prophylactic measures, and both groups will require an antiemetic strategy as part of their perioperative care plan.


A summary of the characteristics of different antiemetic groups follows.


Serotonin (5-HT 3 ) Receptor Antagonists


This group includes ondansetron, dolasetron, granisetron, tropisetron, ramosetron, and palonosetron. They are generally more effective against vomiting than nausea, so to maximize their effectiveness they are better administered at the end of surgery. They have a range of side effects such as headache, elevated liver enzymes, constipation, and prolonged QT interval (dose related). Few case records of clinically significant arrhythmias were linked to 5-HT 3 receptor antagonists. Overall the low incidence of side effects led to their widespread use. Dolasetron is no longer available in the United States.


Neurokinin-1 Receptor Antagonists


These agents are the newest group of antiemetics to find a niche in anesthesia after their introduction for chemotherapy-induced nausea and vomiting. The well-established members are aprepitant, casopitant, and rolapitant.


They have an extended duration of action (48 to 72 hours) so can be used on induction of anesthesia. Their side effects are relatively mild and include dizziness, weakness, and nonspecific mild symptoms. No cardiovascular side effects have been documented.


Corticosteroids


Both dexamethasone and methylprednisolone have been used for managing PONV. Considering their pharmacokinetic profile—mainly their duration of action—they are to be used after induction of anesthesia, and no further doses are recommended if the initial dose is ineffective. Recent studies suggest that higher doses of dexamethasone (8 mg) are more effective. Positive effects on quality of recovery (including quality of pain control) have been documented.


The side effects of their short-term use are limited. Phosphate preparation causes severe perineal itching and pain (50% of patients, females greater than males). Dexamethasone causes an increase in blood glucose 6 to12 hours after a single dose, making it relatively contraindicated in labile diabetic patients.


Butyrophenones


Droperidol and haloperidol are the two main butyrophenones used for PONV management. They are effective when used at the end of surgery. Because of the side-effect profile, they are recommended as rescue therapy only.


Prolongation of QT interval in a pattern and to an extent similar to ondansetron is the most serious side effect (2001 droperidol black box warning by the Food and Drug Administration [FDA]). Sedation occurs in the higher range of doses. Haloperidol has a lower incidence of prolonged QT interval, but its use for PONV is not an FDA-approved indication.


Antihistamines


Dimenhydrinate, meclizine, and cyclizine (United Kingdom) are established feasible antiemetics. There is no consensus regarding the optimum time for their administration. Their side effects are related to their anticholinergic properties (tachycardia, blurred vision, hallucinations, and occasionally urinary retention), especially in the elderly. Sedation is another common side effect.


Anticholinergics


Transdermal scopolamine is the main agent in this category. The patch is effective for up to 24 hours. It can be applied the night before surgery or on the same day. Its side effects are generally mild and include visual disturbances and dizziness.


Antidopaminergics


Phenothiazines such as prochlorperazine and perphenazine are no longer used as antipsychotics. Their use for PONV should be in combination with other agents or as rescue therapy considering the potential serious (and dose-related) side effects. Sedation is comparable to a placebo when used within the recommended dose for PONV. They are also associated with a low incidence of neuroleptic malignant syndrome and anticholinergic side effects.


Metoclopramide


Recent evidence shows poor effectiveness of metoclopramide within the therapeutic dose (10 mg). Effectiveness improves when the dose is increased to 30 mg but still below that of other drug groups. Unfortunately, the incidence of extrapyramidal side effects increases significantly with higher doses (number needed to harm 140).


Acupuncture


Recent literature review has shown that P-6 stimulation using different modalities of acupuncture was associated with lower incidence of PONV and less need for rescue therapy. This effect was maintained both in adults and children and in invasive and noninvasive approaches to acupuncture and was not dependent on the timing of stimulation. Neuromuscular stimulation of the median nerve (particularly in the tetanic mode) has shown similar efficacy.

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Feb 18, 2019 | Posted by in ANESTHESIA | Comments Off on Antiemetics
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