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Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.
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When administered at the end of surgery, 12.5 mg of dolasetron IV is as effective as 25 mg of dolasetron IV, 4 mg of ondansetron IV, and 8 mg of ondansetron IV in preventing emetic symptoms after otolaryngologic surgery and was associated with similar patient satisfaction at a reduced cost. There were no differences in the antiemetic efficacy of the 4 and 8 mg doses of ondansetron.
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Dexamethasone alone and in combination with selective 5-hydroxytryptamine receptor antagonists is of benefit in the prophylaxis of post-operative nausea and vomiting. In this study, the effectiveness of such a combination in comparison to either drug alone is investigated in day case gynaecological surgery. A total of 177 patients were randomized to three treatment groups: dexamethasone 8 mg, ondansetron 4 mg, and dexamethasone 8 mg plus ondansetron 4 mg. The only significant difference between groups was seen in the first 3 h when failure of prophylaxis was more frequent in patients who had received dexamethasone alone (P=0.0085; Fisher's exact probability test). Confidence interval analysis indicates a modest treatment effect for the combination and the decision whether to perform a larger study depends upon whether such an effect is clinically relevant.
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1. Tritiated derivatives of the potent and selective 5-HT3 receptor antagonists GR65630 and LY278584 were used to identify 5-HT3 recognition sites in the rat gastrointestinal tract. 2. Binding studies were carried out in homogenates of the rat oesophagus, the cardia, fundus, body and antrum of the stomach, regions of the small intestine, caecum and large intestine. The specific binding of a single concentration of GR65630 (0.5 nM) defined by granisetron (10 microM) in these areas indicated that the density of 5-HT3 recognition sites varied from 2.4 +/- 1.0 to 10.1 +/- 1.0 fmol mg-1 protein. 3. Saturable binding of [3H]-GR65630 could only be demonstrated in the terminal regions of the small intestine (Bmax in the range of 13.83 +/- 4.54-21.19 +/- 0.89 fmol mg-1 protein; mean +/- s.e. mean) and of high affinity (Kd in the range of 0.42 +/- 0.18-0.79 +/- 0.24 nM). Use of [3H]-LY278584 revealed a similar binding density (Bmax 19.54 +/- 0.26 fmol mg-1 protein) and affinity (Kd 1.04 +/- 0.07 nM) in the terminal small intestine. 4. Binding of [3H]-GR65630 and [3H]-LY278584 to the terminal region of the small intestine was inhibited by 5-HT3 receptor ligands ondansetron and S-zacopride (and 5-hydroxytryptamine), but not by 5-HT1, 5-HT2, catecholamine, gamma-aminobutyric acid and opioid receptor ligands. 5. These data demonstrate that there are regional variations in the density of 5-HT3 recognition sites within the rat gastrointestinal tract. Such data are relevant to the potential use of 5-HT3 receptor ligands to modify secretory and contraction responses in the gastrointestinal system.
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Delirium is highly prevalent among elderly post-operative patients with no pharmacological intervention approved by the Food and Drug Administration for prevention or treatment. We conducted a systematic evidence review to critically appraise literature related to the pharmacotherapy of post-operative delirium. Ten studies fulfilled our inclusion criteria with two interventions for delirium treatment and eight interventions for delirium prevention in post-operative patients. The quality of evidence of delirium treatment studies was poor, whereas the quality of evidence in delirium prevention studies ranges from moderate to high. Delirium treatment studies find similar delirium duration and length-of-stay outcomes between haloperidol and either morphine or ondansetron. Risperidone was found to reduce the conversion of sub-syndromal delirium to delirium in one study compared to placebo. Haloperidol, olanzapine, and ketamine were each found to reduce delirium incidence, whereas rivastigmine had no impact on delirium incidence or duration. Lighter anesthesia as monitored by bi-spectral index led to a decreased delirium incidence. Considering results from studies conducted prior to the dates of this review, the current evidence suggests that certain pharmacologic classes and lighter sedation using BIS monitoring may prevent post-operative delirium, although a conclusive recommendation for clinical practice must await further research.
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We report a case of a teenage boy with cyclical vomiting syndrome (CVS) who was referred to the anesthesia-run postoperative pain service for symptom management. His symptoms were uncontrolled by oral pizotifen prophylaxis and acute therapy with intravenous (IV) hydration and ondansetron. A continuous low dose IV midazolam infusion was added to his treatment regimen (as is instituted for recalcitrant postoperative nausea and vomiting) with benefit, but not total symptom resolution. Recent literature review suggested links between migraine, CVS and adrenergic autonomic dysfunction. Consequently, IV clonidine was administered, in addition, with recovery. This combination was reinstituted successfully on subsequent admissions and emergency department presentations with shortened episode durations from 4-5 days to 16-48 h. It is uncertain if clonidine's sympatholytic effects were significantly beneficial or if associated sedation or natural resolution were contributors. Many agents have been used in CVS therapy but no trials have been done. Neither midazolam nor clonidine has been reported previously as used in the treatment of CVS. The apparent success of this combination raises possibilities both for future trials and research into the pathogenesis of CVS.
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Of 115 questionnaires, 66 respondents (57%) returned the questionnaires. Most of the respondents (74%) worked in a university hospital. Forty-two percent practiced exclusively in obstetric-gynaecology department. Fifty-six percent were anaesthetists for more than 20 years. Eighty-five percent of the physicians were well-informed about the SFAR's PONV prevention guidelines. Thirty seven percent of respondents assessed Apfel score systematically for all their patients. The percentages, which didn't calculate the probability of PONV with Apfel score or calculated only in cases of PONV history or travel sickness were 18% and 45% respectively. In cases of two or more risk factors, 63% used droperidol, dexamethasone and ondansetron in double or triple combinations.
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Seventy-six patients with congenital LQTS were identified who had a total of 114 anesthetic encounters. Of the 114 anesthetic encounters, there were 3 AEs, 2 definite and 1 probable AE, for an incidence of 2.6%. The events occurred in boys (aged 11, 13, and 15 years) while undergoing noncardiac surgery under volatile general anesthesia. All were receiving β-blocker therapy preoperatively. The AEs occurred in close proximity to the administration of reversal drugs (anticholinesterase/anticholinergic combinations) and the antiemetic ondansetron. The events occurred during emergence from anesthesia, and exclusively in the group of patients who received both reversal drugs and ondansetron. All were treated successfully with short-term antiarrhythmic drug therapy and discharged the next morning.
Overall, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients.
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DA-9701, a new prokinetic agent for the treatment of functional dyspepsia, is formulated with Pharbitis semen and Corydalis tuber. This study wasconducted to determine the pharmacological action of DA-9701 and to identify the receptors involved in DA-9701 -induced contractile responsesin the feline gastric corporal, fundic and antral circular smooth muscle. Concentration-response curve to DA-9701 was established. The tissue trips were exposed to methylsergide, ketanserin, ondansetron, GR 113808, atropine and dopamine before administration of DA-9701. The contractile force was determined before and after administration of drugs by a polygraph.DA-9701 enhanced the spontaneous contractile amplitude of antrum, corpus and fundus. However, it did not change the spontaneous contractile frequency of antrum and corpus, but concentration-dependently reduced that of fundus. In the fundus, DA-9701 -induced tonic contractions were inhibited by dopamine, methylsergide, ketanserine, ondansetron or GR 113808 respectively, but not by atropine, indicating that the contractile responses are mediated by multiple receptors: 5-HT2, 5-HT3, 5-HT4, and dopamine receptors. In the corpus, DA-9701-induced contractions were blocked by atropine, dopamine or GR 113808, but not by methysergide, ketanserin or ondansetron, indicating that they are involved in receptors on both, smooth muscles and neurons: 5-HT4 and dopamine receptors. However, contractile responses to DA-9701 are mainly mediated by dopamine receptors in the antrum. These results suggest that DA-9701 has important roles in gastric accommodation by enhancing tonic activity of fundus, and in gastric emptying and gastrointestinal transit by phasic contractions of corpus and antrum mediated by multiple receptors.