The role of 5-H[T.sub.3] receptor antagonists in preventing: postoperative nausea and vomiting

AORN Journal, Jan, 2006 by Thomas Board, Rhonda Board

Postoperative nausea and vomiting (PONV), frequently occurring sequelae of perioperative anesthetic administration, can be distressing to both patients and clinicians. (1) Prevention and treatment of PONV are key patient care issues that greatly affect comfort and satisfaction with care. In a survey of 101 patients, the most undesirable surgical outcome reported was vomiting, which ranked even higher than pain. (1) Patients have described PONV as more debilitating than the surgery itself with symptoms that may continue for up to 24 hours. (2)

Studies and meta-analyses of the incidence of PONV show high variability of PONV rates after both inpatient and outpatient surgery. (3) As many as 70% of patients may experience nausea and/or vomiting. (4) Among nearly 16,000 patients interviewed at four hospitals, the incidence of postoperative nausea was 27% with 13% characterized as severe while the overall incidence of postoperative vomiting was 17%. (5)

Predictive risk factors for PONV have been identified that aid in both identifying high-risk patients and developing strategies to reduce the occurrence of PONV. This article describes the pathophysiology of PONV, explains the clinical pharmacology of 5-[HT.sub.3] antagonists, reviews the published literature of 5-[HT.sub.3] antagonist therapies used for PONV, and provides recommendations for nursing management of PONV.

PATHOPHYSIOLOGY AND CLINICAL PHARMACOLOGY

Vomiting is a protective mechanism that rids the body of noxious chemicals and prevents further ingestion of toxic substances. The process can be broken down into three phases:

* nausea (ie, the inclination to vomit);

* retching (ie, an involuntary effort to vomit); and

* vomiting (ie, the actual ejection of contents from the stomach through the mouth). (2,4,6)

Serotonin (ie, 5-hydroxytryptamine [5-HT]) is a hormone and a neurotransmitter that inhibits gastric secretion. It is found in high concentrations predominantly in enterochromaffin cells throughout the gastrointestinal (GI) tract, in specific areas of the central nervous system (CNS), and in smaller concentrations in platelets. There are many different receptor types for serotonin, but the specific target receptor subtype for nausea and vomiting is subtype 3 (ie, 5-[HT.sub.3]). The 5-[HT.sub.3] receptors are located both peripherally on the parasympathetic terminals in the GI tract, including vagal and splanchnic afferents, and centrally in the CNS. The largest density of 5-[HT.sub.3] receptors is found in the CNS, specifically in the nucleus tractus solitarii (NTS) and in the chemoreceptor trigger zone (CTZ) where 5-[HT.sub.3] antagonists are thought to have the greatest effect. (2,4,6)

The vomiting center is the central emesis center located in the midbrain, and it is responsible for signaling nausea and/or coordinating emesis (Figure 1). Although the CTZ and NTS have direct input to the vomiting center and receive input from various receptors in the body, they specifically receive vagally-mediated input from the GI tract. The CTZ, located in the area postrema at the bottom of the fourth ventricle of the brain, sits between the blood-brain barrier, thereby enabling it to constantly monitor blood and cerebral spinal fluid for toxic substances; the NTS sits inside the blood-brain barrier in the medulla oblongata. (2,4,6)

[FIGURE 1 OMITTED]

A 5-[HT.sub.3] receptor antagonist acts by binding either reversibly (ie, temporarily) or irreversibly (ie, permanently) to the 5-[HT.sub.3] receptor. If the antagonist reversibly binds to the receptor site, it is considered to have a low binding affinity, and it may be bumped off by competition from other molecules that compete for the site or by other physical mechanisms. If the receptor irreversibly binds to the receptor site, it is bound for the life of the receptor and is considered to have a high receptor binding affinity. Thus, the higher the binding affinity, the more potent the medication.

The 5-[HT.sub.3] receptor is the key target for treatment and prevention of postoperative nausea. In PONV, increased amounts of circulating chemicals stimulate the CTZ and NTS, thereby leading to the release of serotonin. These chemicals may come from the inhaled gases, narcotics, and reversal agents that are used during the surgery and in the postanesthesia care unit (PACU). During GI surgery, abdominal surgery, or laparoscopic procedures, air is blown into the abdominal cavity, which may stretch mechanoreceptors in the intestine and irritate the enterochromaffin cells. These cells lyse and release large amounts of vasoactive substances, including serotonin, which consequently activate the 5-[HT.sub.3] receptors and send a signal to the CTZ and the NTS. (2,4,6)

The process for triggering nausea and emesis is complex because stimulation of the vomiting center may come from several pathways and multiple neurotransmitters not mediated by the 5-[HT.sub.3] receptor. Although the 5-[HT.sub.3] receptor is a major target during surgery, two pathways other than the NTS and CTZ have direct input into the vomiting center: the vestibular apparatus and the cerebral cortex. The vestibular apparatus (ie, inner ear) is responsible for motion. The higher learning centers in the cerebral cortex receive sensory inputs from the body (ie, pain, smell, sight) and from behavior (ie, memory, fear, dread, anticipation). In addition, other neurotransmitters (ie, histamine, dopamine, acetylcholine,