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Optimum management of nausea and vomiting in cancer chemotherapy.

Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. It must be admitted, however, that our approach is for the most part still empirical. Selecting an antiemetic programme is not a simple task. The emetogenic potential of the chemotherapy being used, the presence of coexisting diseases, the potential toxicity of the antiemetic drug and whether antiemetic therapy is to take place in the hospital or in an outpatient setting, the familiarity of the clinician with the various antiemetic therapies, and cost are all factors which need to be considered. Although phenothiazines remain the standard treatment, they are of little value against chemotherapy programmes that produce moderate or severe problems. Newer pharmacological approaches including butyrophenones, cannabinoids, metoclopramide, high-dose corticosteroids, and benzodiazepines have shown increased antiemetic efficacy, as have combinations of these agents which are directed against multiple sites of emetogenic activity. The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.

Antineoplastic Agents↗

ORT and vomiting. Reply to Tambawal letter.

Oral rehydration therapy (ORT) can be considered as both curative and preventive with regard to dehydration due to diarrhea. When given to a dehydrated patient, usually in the form of oral rehydration salts, its purpose is to correct (cure) the dehydration by restoring normal amounts of water and salts to the body. However, when given soon after the onset of diarrhea, before dehydration develops, usually as a homemade solution, its purpose is to prevent the reoccurrence of dehydration. Vomiting happens frequently during diarrhea, especially when the illness is caused by rotavirus or cholera. Vomiting can occur, or continue, during the 1st hour or 2 of ORT, after which it will usually diminish or stop. When vomiting occurs during ORT, fluid administration should be continued after waiting 10 minutes but given more slowly in sips at short intervals. Although it may appear that a large amount of rehydration fluid has been vomited, most of what is given is actually retained, benefiting the patient. Antiemetics, such as chlorpromazine should not be given because (i) they have undesirable side effects, such as drowsiness, which can interfere with the continuation of ORT, and (ii) the vomiting will usually subside as ORT is continued.

Biology↗

Green vomiting in the first 72 hours in normal infants.

From June 1980 to September 1984, forty-five newborns (weight greater than or equal to 2000 g), initially presumed normal, were seen with bilious vomiting in the first 72 hours and were prospectively followed up. Nine (20%) required surgical intervention, five (11%) had nonsurgical obstruction such as meconium plug or left microcolon, and the remaining 31 (69%) had idiopathic bilious vomiting. Infants with idiopathic bilious vomiting had a benign transient course and resumed feedings by 1 week of age; 30 of the 31 had normal or nonspecific findings on initial plain abdominal roentgenogram. Specific findings on the initial plain abdominal roentgenogram were noted in five infants, and four (80%) of these had a lesion requiring surgical intervention; 56% (5/9) of neonates with surgical lesions had normal or nonspecific findings on the plain abdominal roentgenograms. None developed bowel ischemia or midgut infarction secondary to a volvulus as they were identified by contrast studies shortly after the initial episode of bilious vomiting. Although the majority of "normal" neonates with bilious vomiting do not have a surgical lesion, this study indicates that 56% of surgical cases will be missed if contrast studies are not done.

Age Factors↗

Testing the psychogenic vomiting diagnosis. Four pediatric patients.

We treated four patients with chronic vomiting during childhood in whom a tentative diagnosis of psychogenic vomiting was made after an extensive evaluation. In each case, the diagnosis was reconsidered during the course of treatment, as observations about the patients and their response to interventions accumulated. In three instances, these observations did not fit those expected if the diagnosis of psychogenic vomiting was correct. This led to a reexamination of the organic evaluation and the discovery of an undiagnosed organic contribution to the vomiting. In the fourth patient, gastric emptying studies confirmed that there was a strong psychological contribution to the vomiting, and helped to more carefully define this contribution. Family and individual psychotherapy and treatment were aided by the greater clarity in diagnosis.

Child↗

Control of cancer chemotherapy-induced nausea and vomiting.

With increasingly effective cancer chemotherapy, the control of chemotherapy-induced nausea and vomiting has become more important. These unpleasant side effects can be so severe that patients delay or stop potentially curative therapy. Phenothiazines and butyrophenones have been the mainstays of most antiemetic therapy but unfortunately have only partially controlled nausea and vomiting. Recently, renewed interest in the control of nausea and vomiting has led to the introduction of additional classes of agents. Cannabinoids appear to be superior to phenothiazines as antiemetics, but must be given in doses that also cause central nervous system side effects. Metoclopramide, given in high doses (1.0-3.0 mg/kg) has proven to be a major advance in the control of nausea and vomiting induced by cisplatin. Glucocorticoids may be useful, particularly when combined with other agents. There has been recent recognition of the importance of anticipatory nausea and vomiting, and attempts to control this through behavioral modification techniques have met with some success.

Antineoplastic Agents↗

Randomized clinical trial of the effect of preoperative dexamethasone on nausea and vomiting after laparoscopic cholecystectomy.

BACKGROUND: Preoperative dexamethasone may reduce disabling symptoms such as pain, nausea and vomiting after laparoscopic cholecystectomy. METHODS: This was a randomized, double-blind, placebo-controlled trial. Between March and December 2004, 101 patients undergoing laparoscopic cholecystectomy were randomized to receive 8 mg dexamethasone (n = 49) or placebo (n = 52) intravenously before surgery. Six patients were excluded from the study. All patients received a standardized anaesthetic, surgical and multimodal analgesic treatment. The primary endpoints were: first, postoperative nausea, vomiting and pain; second, postoperative analgesic and antiemetic requirements. The pain scores (visual analogue and verbal response scales), the episodes of nausea (verbal response scale) and vomiting were recorded at 1, 3, 6 and 24 h, respectively, after the operation. Analgesic and antiemetic requirements were also recorded. RESULTS: No apparent drug side-effects were noted. Seven patients (14 per cent) in the treatment group reported nausea and vomiting compared with 24 (46 per cent) in the control group (P = 0.001). In the group of patients treated with dexamethasone, five (10 per cent) required antiemetics versus 23 (44 per cent) of those receiving placebo (P < 0.001). No difference in postoperative pain scores and analgesic requirements was detected between groups. CONCLUSION: Preoperative dexamethasone reduces postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy, with no side-effects, and may be recommended for routine use.

Analgesics↗

Relationships between features associated with vomiting in purging-type eating disorders.

OBJECTIVE: Vomiting is a pernicious symptom of eating disorders. We explored the relation between the symptom of vomiting and features of eating disorder course and severity, personality traits, and Axis I and II comorbidity in individuals with purging-type eating disorders. METHOD: The sample included participants from the multisite, international Price Foundation Genetic Studies, who had an eating disorder diagnosis (anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified) and had data available for the frequency of purging behaviors (n = 1,048). Axis I disorders, personality disorders, trait anxiety, perfectionism, and temperament and character dimensions were included as possible correlates. RESULTS: The presence of vomiting was associated with less regular laxative use, lower self-directedness, organization, personal standards, and higher novelty seeking. CONCLUSION: Vomiting remains a prevalent and potentially destructive symptom of eating disorders, with significant dental and medical morbidity. Our findings suggest that certain clinical and personality variables distinguish individuals with purging-type eating disorders who vomit from those who do not, although there were no marked differences in Axis I or II comorbidity. Specifically targeting treatment to decrease duration of exposure to this dangerous symptom continues to be an important clinical objective.

Adolescent↗

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting--the Nordic experience.

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical analysis of post-traumatic vomiting.

Post-traumatic vomiting was clinically analyzed. One hundred and forty seven patients with head injury came to our hospital consecutively from April 1991 to August 1991. Of 147 patients, 26 exhibited vomiting post-traumatically. The incidence of loss of consciousness, that of fractures on plain X-ray films, and that of traumatic intracranial lesions demonstrated on CT were compared between two patient groups, i.e., a group of patients with post-traumatic vomiting and another one without it. None of them were revealed to be significantly different between the two groups, respectively. It was concluded from the results that the existence of post-traumatic vomiting implied neither severe traumatic impact nor serious intracranial damage. The plausible mechanisms of post-traumatic vomiting are discussed, taking account of the statistical data on the patients' age, sites of impact, and past histories.

Adolescent↗

Extrinsic nervous control of retrograde giant contraction during vomiting in conscious dogs.

Neural mechanisms controlling retrograde giant contraction during vomiting were studied in six conscious dogs with implanted strain gauge force transducers. The small intestine was divided into proximal (P), middle (M), and distal (D) segments. These segments were transplanted on intact mesenteric neurovascular pedicles. In three dogs, M and D segments were interchanged (group A). In three dogs, P and M segments were interchanged (group B). Before transplantation, apomorphine-induced vomiting caused retrograde giant contractions, starting from the M segment and rapidly migrating to the stomach. However, in group A, even after recovery of interdigestive migrating contractions migration, retrograde giant contractions during vomiting always originated in the distally interchanged M segment and jumped to the P segment without migration to the D segment. In group B, the retrograde giant contraction always originated in the proximally interchanged M segment and successively occurred in the distally interchanged P segment. We conclude that origination and migration of retrograde giant contractions are extrinsically controlled. These motor events during vomiting are thought to be a specific motor function that does not exist in the lower small intestine, and retrograde giant contraction during vomiting may originate in the mid-small intestine.

Animals↗

Perioperative gastric aspiration increases postoperative nausea and vomiting in outpatients.

The efficacy of aspiration of gastric contents to reduce postoperative nausea and vomiting was investigated in a controlled randomized, double-blind study of 265 outpatients. Patients in the treated group had their stomachs aspirated with an orogastric tube. In the control group no tube was inserted. Data on the incidence of nausea and vomiting were collected in the recovery room, the day surgery unit and the day after surgery. The overall incidence of postoperative nausea and vomiting was comparable in the two groups. It was also comparable in the recovery room and the day surgery unit. However, treated patients had a higher incidence of both nausea (26.5% vs 12.0%, P < 0.005) and vomiting (16.7% vs 6.8%, P < 0.02) after their discharge from the day surgery unit. We conclude that aspiration of gastric contents with an orogastric tube does not decrease postoperative nausea and vomiting in outpatients and may increase it after discharge of the patient.

Adult↗

Subhypnotic propofol does not treat postoperative vomiting in children after adenotonsillectomy.

PURPOSE: To investigate the efficacy of a subhypnotic dose of propofol to treat vomiting in children after adenotonsillectomy. METHODS: Two hundred and fifty-two children, aged 2-12 yr, underwent a standardized anaesthetic opioid administration, and postoperative care after adenotonsillectomy, adenoidectomy or tonsillectomy. A prospective, double-blinded, placebo-controlled study was performed in 70 of the patients who retched or vomited after surgery and who had intravenous access. Patients were assigned randomly to receive either 0.2 mg.kg-1) propofol (n = 35), or placebo (intralipid 10%, n = 35). RESULTS: The overall incidence of vomiting during the first 18-24 hr was 50%. Of those who had received propofol after the first episode of vomiting, 63% relapsed requiring a rescue antiemetic compared with 57% of those who had received intralipid (P = NS). Of the children who received propofol, 54% experienced pain on injection and 46% were mildly sedated compared with 3% and 11%, respectively, in the placebo group (P < 0.003). CONCLUSION: We conclude that an intravenous bolus of 0.2 mg.kg-1 propofolis not effective in the treatment of postoperative vomiting in children after adenotonsillectomy when a standardized anaesthetic with thiopentone, halothane, nitrous oxide, and 1.5 mg.kg-1 codeine phosphate is used, but it does cause sedation and pain on injection.

Adenoidectomy↗

Prophylactic Diclectin reduces the incidence of postoperative vomiting.

BACKGROUND: Diclectin(R) (DCL) is an effective antiemetic used for relief of nausea and vomiting in pregnancy. It is unknown whether DCL is effective in the prevention of postoperative nausea and vomiting (PONV). METHODS: We conducted a randomized, stratified, double-blind placebo-controlled trial to examine the incidence of PONV in women undergoing elective laparoscopic tubal ligation in the day surgery setting. DCL (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) was administered orally the night before surgery, the morning of surgery, and upon hospital discharge. RESULTS: We enrolled 146 women in the trial, 127 of whom were included in the effectiveness analysis and 102 of whom were included in the efficacy analysis. We did not detect a difference in the incidence of nausea and vomiting in the first six hours postoperatively after adjusting for additional antiemetics administered. Patients receiving DCL as compared with placebo were significantly less likely to experience vomiting six to 24 hr postoperatively [5/59 (8.5%) vs 14/55 (25.4%), P < 0.017]. Treated patients tended to return to work earlier than those who received placebo (1.74 vs 3.7 days P = NS). CONCLUSION: Perioperative oral DCL reduces the incidence of postoperative vomiting in women undergoing elective laparoscopic tubal ligation, and may accelerate return to work.

Adult↗

Dexamethasone prophylaxis of nausea and vomiting after epidural morphine for post-Cesarean analgesia.

PURPOSE: To determine the minimum effective dose of dexamethasone in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia. METHOD: One hundred and eighty parturients (n=45 in each of four groups) requiring epidural morphine for post-Cesarean analgesia were enrolled in this randomized, double-blinded, placebo-controlled study. At the end of surgery, parturients received either dexamethasone, at doses of 10 mg, 5 mg, 2.5 mg, or saline i.v.. Three milligrams epidural morphine were given to all parturients for postoperative analgesia. The incidence of PONV and side effects were estimated for 24 hr after delivery by blinded, trained nurse anesthetists. RESULTS: Parturients who received dexamethasone, either 10 mg or 5 mg were different from those who received saline alone in the following parameters: the total incidence of nausea and vomiting, incidence of > 4 vomiting episodes, number the of parturients requiring rescue antiemetics, and the total number of parturients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences between dexamethasone 10 mg and 5 mg were not significant. Dexamethasone 2.5 mg was partially effective. CONCLUSION: Dexamethasone, 5 mg i.v., is suggested as the minimum effective dose in preventing nausea and vomiting associated with epidural morphine for post-Cesarean analgesia.

Adult↗

5-HT3 receptor antagonists vs traditional agents for the prophylaxis of postoperative nausea and vomiting.

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.

Antiemetics↗

Effect of drainage on postoperative nausea, vomiting, and pain after laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is associated with a high incidence of postoperative pain, nausea, and vomiting. Pneumoperitoneum created during the operation and residual gas after the operation are two of the factors in postoperative pain and nausea. We studied the effects of a subdiaphragmatic gas drain, which is intended to decrease the residual gas, on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy. PATIENTS AND METHODS: Seventy patients were randomized into two demographically and clinically comparable groups: drainage and control. Postoperative pain, nausea, and vomiting were measured by verbal grading and visual analog scale 2-72 h postoperatively. Analgesic and antiemetic use and incidence of retching, vomiting and other complaints were also recorded. RESULTS: Subdiaphragmatic drain effectively reduced the incidence and amount of subdiaphragmatic gas bubble. The incidence and severity of nausea was lower in the drainage group at 72 h. Although severity of pain was lower at 8 and 12 h in the drainage group, the difference was not significant. There was also no difference between the groups in regard to analgesic and antiemetic use. CONCLUSIONS: Subdiaphragmatic drain offers only minor, if any, benefit on postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy, and this effect is probably clinically irrelevant.

Adult↗

Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines.

As many as 40-80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting, depending on the site of irradiation. Fractionated RT may involve up to 40 fractions over a 6-8 weeks period, and prolonged symptoms of nausea and vomiting could affect quality of life. Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiotherapy. Nausea and vomiting are often underestimated by radiation oncologists. Incidence and severity of nausea and vomiting depend on RT-related factors (single and total dose, fractionation, irradiated volume, radiotherapy techniques) and patient-related factors (gender, general health of the patient, age, concurrent or recent chemotherapy, psychological state, tumor stage). Current antiemetic guidelines prescribe the emetogenicity of radiotherapy regimens and recommend the use of 5-HT(3) antagonists with or without a steroid for prophylaxis in moderately and highly emetogenic treatment (MASCC, ASCO, ASHP, NCCN). The new proposed guidelines summarise the updated data from the literature and take into consideration the existing guidelines. According to the irradiated area (the most frequently studied risk factor), the proposed guidelines are divided into four levels of emetogenic risk: high, moderate, low and minimal. They offer guidance to prescribing physicians for effective antiemetic therapies in RINV.

Antiemetics↗

Treatment of nausea and vomiting in advanced cancer.

Nausea and vomiting unrelated to chemotherapy is common in advanced cancer patients. The etiology of nausea and vomiting may from evident by the pattern of vomiting, associated symptoms, review of medications and physical examination. Radiographic studies are particularly helpful if bowel obstruction is suspected or central nervous system metastases are a possibility. Laboratory studies are helpful in a minority of cases. Multiple classes of medications are available to palliate nausea and vomiting. Classes of agents are discussed, pharmacology and cost being among the aspects covered. A four-step approach to the medical management of nausea and vomiting is presented.

Antiemetics↗