Who is at risk for postdischarge nausea and vomiting after ambulatory surgery?

BACKGROUND: About one in four patients suffers from postoperative nausea and vomiting. Fortunately, risk scores have been developed to better manage this outcome in hospitalized patients, but there is currently no risk score for postdischarge nausea and vomiting (PDNV) in ambulatory surgical patients. METHODS: We conducted a prospective multicenter study of 2,170 adults undergoing general anesthesia at ambulatory surgery centers in the United States from 2007 to 2008. PDNV was assessed from discharge until the end of the second postoperative day. Logistic regression analysis was applied to a development dataset and the area under the receiver operating characteristic curve was calculated in a validation dataset. RESULTS: The overall incidence of PDNV was 37%. Logistic regression analysis of the development dataset (n=1,913) identified five independent predictors (odds ratio; 95% CI): female gender (1.54; 1.22 to 1.94), age less than 50 yr (2.17; 1.75 to 2.69), history of nausea and/or vomiting after previous anesthesia (1.50; 1.19 to 1.88), opioid administration in the postanesthesia care unit (1.93; 1.53 to 2.43), and nausea in the postanesthesia care unit (3.14; 2.44-4.04). In the validation dataset (n=257), zero, one, two, three, four, and five of these factors were associated with a PDNV incidence of 7%, 20%, 28%, 53%, 60%, and 89%, respectively, and an area under the receiver operating characteristic curve of 0.72 (0.69 to 0.73). CONCLUSIONS: PDNV affects a substantial number of patients after ambulatory surgery. We developed and validated a simplified risk score to identify patients who would benefit from long-acting prophylactic antiemetics at discharge from the ambulatory care center.

Perspectives on transdermal scopolamine for the treatment of postoperative nausea and vomiting.

Transdermal scopolamine, a patch system that delivers 1.5 mg of scopolamine gradually over 72 hours following an initial bolus, was approved in the United States in 2001 for the prevention of postoperative nausea and vomiting (PONV) in adults. Scopolamine (hyoscine) is a selective competitive anatagonist of muscarinic cholinergic receptors. Low serum concentrations of scopolamine produce an antiemetic effect. Transdermal scopolamine is effective in preventing PONV versus placebo [relative risk (RR)=0.77, 95% confidence interval (CI), 0.61-0.98, P = 0.03] and a significantly reduced risk for postoperative nausea (RR=0.59, 95% CI, 0.48-0.73, P < 0.001), postoperative vomiting (RR=0.68, 95% CI, 0.61-0.76, P < 0.001), and PONV (RR 0.73, 95% CI, 0.60-0.88, P = 001) in the first 24 hours after the start of anesthesia.

Anesthetic Routines: The Anesthesiologist's Role in GI Recovery and Postoperative Ileus.

All patients undergoing bowel resection experience postoperative ileus, a transient cessation of bowel motility that prevents effective transit of intestinal contents or tolerance of oral intake, to varying degrees. An anesthesiologist plays a critical role, not only in the initiation of surgical anesthesia, but also with the selection and transition to effective postoperative analgesia regimens. Attempts to reduce the duration of postoperative ileus have prompted the study of various preoperative, perioperative, and postoperative regimens to facilitate gastrointestinal recovery. These include modifiable variables such as epidural anesthesia and analgesia, opioid-sparing anesthesia and analgesia, fluid restriction, colloid versus crystalloid combinations, prokinetic drugs, and use of the new peripherally acting mu-opioid receptor (PAM-OR) antagonists. Review and appropriate adaptation of these multiple modifiable interventions by anesthesiologists and their surgical colleagues will facilitate implementation of a best-practice management routine for bowel resection procedures that will benefit the patient and the healthcare system.

The opioid component of delayed gastrointestinal recovery after bowel resection.

INTRODUCTION: Patients undergoing bowel resection or other major abdominal surgery experience a period of delayed gastrointestinal recovery associated with increased postoperative morbidity and longer hospital length of stay. Symptoms include nausea, vomiting, abdominal distension, bloating, pain, intolerance to solid or liquid food, and inability to pass stool or gas. The exact cause of delayed gastrointestinal recovery is not known, but several factors appear to play a central role, namely the neurogenic, hormonal, and inflammatory responses to surgery and the response to exogenous opioid analgesics and endogenous opioids. DISCUSSION: Stimulation of opioid receptors localized to neurons of the enteric nervous system inhibits coordinated gastrointestinal motility and fluid absorption, thereby contributing to delayed gastrointestinal recovery and its associated symptoms. Given the central role of opioid analgesics in delayed gastrointestinal recovery, a range of opioid-sparing techniques and pharmacologic agents, including opioid receptor antagonists, have been developed to facilitate faster restoration of gastrointestinal function after bowel resection when used as part of a multimodal accelerated care pathway. This review discusses the etiology of opioid-induced gastrointestinal dysfunction as well as clinical approaches that have been evaluated in controlled clinical trials to reduce the opioid component of delayed gastrointestinal recovery.

Evaluation of a novel topical essential oxygen oil for the treatment of pain in acute tendinopathy and sprains.

Topical analgesics may play an increasingly important role in managing acute and chronic pain as acetaminophen, NSAIDs, and opioid drugs come under heightened scrutiny. This article reviews studies about essential oxygen oil, a topical over-the-counter (OTC) analgesic new to the American market but available for many years in Europe. Prospective studies evaluating the oil's safety and efficacy in acute and chronic pain patients, a dermatological study in which healthy subjects served as their own controls, and a post-marketing surveillance study were considered. These studies found the novel essential oxygen oil to be safe and effective in a variety of acute and chronic pain syndromes as well as being well tolerated with few side effects. Its mechanism of action is not understood and further study is warranted. Essential oxygen oil is safe and effective for the treatment of pain associated with many common conditions, including tendinopathy, arthritis, sprains, and others.

Opioid-induced constipation negatively impacts pain management, productivity, and health-related quality of life: findings from the National Health and Wellness Survey.

OBJECTIVE: To characterize the impact of opioid-induced constipation (OIC) on healthcare resource use, work productivity, and health-related quality of life (HRQOL) in patients receiving chronic opioid therapy. DESIGN: Data were collected via Internet questionnaires during the international National Health and Wellness Survey (NHWS) 2004 from individuals aged > or = 18 years who reported taking opioids for > or = 6 months. Healthcare resource utilization, Work Productivity, and Activity Impairment, and Short-Form 8 (SF-8) questionnaire responses were compared between those who did or did not report OIC. RESULTS: Data were available from 2,430 individuals receiving opioids, of whom 359 reported OIC. Participants with OIC reported significantly more physician visits (mean difference 3.84 visits; p < 0.05) and alternative care provider visits (mean difference 1.73 visits; p < 0.05) over the previous 6 months than those without OIC; however, no significant differences in emergency room visits or number of days of hospitalization were observed. Respondents with OIC also reported significantly greater time missed from work, impairment while working, overall work impairment, and activity impairment (p < 0.05 for all comparisons). HRQOL scores were significantly lower in the OIC group than those without OIC on both the physical and mental components of the SF-8 questionnaire (p < 0.05 for both comparisons). CONCLUSIONS: The survey results reflect a negative impact of OIC on individuals' HRQOL and on society in terms of healthcare resource use and work productivity beyond that imposed by patients' pain conditions. These findings indicate a need for effective treatment for opioid-induced constipation in patients receiving chronic opioid therapy.

Peripherally acting mu-opioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability.

Postoperative ileus (POI), a transient cessation of coordinated bowel function after surgery, is an important health care problem. The etiology of POI is multifactorial and related to both the surgical and anesthetic pathways chosen. Opioids used to manage surgical pain can exacerbate POI, delaying gastrointestinal (GI) recovery. Peripherally acting mu-opioid receptor (PAM-OR) antagonists are designed to mitigate the deleterious effects of opioids on GI motility. This new class is investigational for POI management with the goal of accelerating the recovery of upper and lower GI tract function after bowel resection. In this review, we summarize the mechanisms by which POI occurs and the role of opioids and opioid receptors in the enteric nervous system, discuss the mechanism of action of PAM-OR antagonists, and review clinical pharmacology and Phase II/III POI trial results of methylnaltrexone and alvimopan. Finally, the role of anesthesiologists in managing POI in the context of a multimodal approach is discussed.

The role of neurokinin-1 receptor antagonists for the management of postoperative nausea and vomiting.

PURPOSE OF REVIEW: To review the characteristics of neurokinin-1 receptor antagonists and their potential role in the management of postoperative nausea and vomiting. RECENT FINDINGS: Neurokinin-1 antagonists compete with substance P, an endogenous ligand with a high density of receptors in the area postrema and the nucleus tractus solitarii, believed to be involved in terminal emetic pathways. Experimental data provide evidence for efficacy against a wide range of peripheral and central emetic stimuli and clinical trials confirm that neurokinin-1 antagonists have significantly higher efficacy against vomiting than all other antiemetics, with relative risk reductions of over 50%. In fact, aprepitant - the first neurokinin-1 antagonist approved by the US Food and Drug Administration - provides superior protection against postoperative vomiting compared with ondansetron, and the same appears to be true for other drugs of this class. However, efficacy against nausea does not appear to be superior to other antiemetics, so that composite outcomes that are driven by nausea (e.g. complete response) disguise the unique anti-vomiting efficacy. SUMMARY: Postoperative vomiting can lead to rare but serious complications. Neurokinin-1 receptor antagonists are significantly more efficacious against postoperative vomiting than other antiemetics. Because the benefit in terms of absolute risk reduction is critically dependent on the patient's baseline risk, it is recommended to use a validated risk score to identify patients who will benefit most from prophylaxis using neurokinin-1 receptor antagonists.

Alvimopan: a peripherally acting mu-opioid receptor antagonist.

Postoperative ileus (POI), a transient cessation of coordinated bowel motility after surgery, is an important factor in extending the length of hospital stay. The etiology of POI is multifactorial, and related to both the surgical and anesthetic pathways chosen. Additionally, opioids used to manage non-cancer-related and cancer-related chronic pain may also decrease gastrointestinal (GI) motility resulting in opioid-induced bowel dysfunction (OBD). Postoperative ileus has been associated with prolonged hospital stay and readmission, and thus may increase the overall hospital costs per patient with POI. Alvimopan, a peripherally acting mu-opioid receptor antagonist, accelerated time to GI recovery and reduced postoperative hospital length of stay in phase III POI clinical trials and improved symptoms of OBD compared with placebo in phase II/III clinical trials. The U.S. Food and Drug Administration is currently evaluating alvimopan for the management of POI after bowel resection. Alvimopan may provide clinically meaningful benefits to patients and may lower the economic burden of POI to the healthcare system.

Meta-analysis of the safety of 5-HT3 antagonists with dexamethasone or droperidol for prevention of PONV.

BACKGROUND: Antiemetic guidelines recommend a combination of serotonin (5-HT3) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid. OBJECTIVE: To assess the safety profiles of 5-HT3 receptor antagonist (5-HT3RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV). METHODS: A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966-September 2005) using the key terms 5-HT3, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT3RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT3RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with 95% confidence intervals were calculated to determine the incidence rates of all adverse events in RCTs using 5-HT3RA monotherapy and combination therapies. Overall effect sizes for frequently reported adverse events were estimated by pooling ORs using fixed- and random-effect models. RESULTS: Pooled ORs (OR(pooled)) for adverse events with 5-HT3RA/dexamethasone versus 5-HT3RA for PONV prophylaxis were not significant for any reported adverse events or the overall incidence of adverse events; 5-HT3RA/droperidol versus 5-HT3RA was significant only for decreased headache incidence (fixed model: OR(pooled) 0.35; 95% CI 0.18 to 0.69). The OR(pooled) for 5-HT3RA/dexamethasone versus dexamethasone was not significant for any reported adverse events except headaches (fixed model OR(pooled) 1.75; 95% CI 1.01 to 3.03), none of which was serious. OR(pooled) for 5-HT3RA/droperidol versus droperidol was not significant for any reported adverse events. Avascular necrosis, occult infection, and delayed wound healing were not observed with either combination therapy. Cardiac abnormalities were observed with 5-HT3RA/droperidol therapy. CONCLUSIONS: This meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT3RA.

Alvimopan for the management of postoperative ileus.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and administration of alvimopan, a peripherally acting mu-opioid receptor antagonist, in the management of postoperative ileus (POI). DATA SOURCES: A literature search (1980-October 2004) applying the terms alvimopan, ADL 8-2698, and LY246736 was conducted using MEDLINE. Information was also obtained from scientific congress abstracts and data on file with the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Studies and abstracts investigating alvimopan and POI were considered for inclusion; however, they were restricted to English-language articles. DATA SYNTHESIS: Alvimopan is a novel, peripherally acting mu-opioid receptor antagonist that is currently under evaluation for the management of POI. POI presents significant clinical challenges that can delay patient recovery and contribute to increased morbidity and prolonged hospitalization after surgery. Clinical trials have demonstrated that alvimopan, at oral doses of 6 and 12 mg, can accelerate time to recovery of gastrointestinal (GI) function and time to hospital discharge following abdominal surgery. The incidence of adverse events with alvimopan therapy was shown to be similar to that of placebo. CONCLUSIONS: Alvimopan is well tolerated and effective at accelerating GI recovery and time to discharge in patients who have undergone bowel resection or hysterectomy when administered prior to surgery and twice daily thereafter until discharge or for up to 7 days. Alvimopan potentially offers significant benefits for patients with POI over currently available treatments.