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Effect of topical local anesthetic application to skin harvest sites for pain management in burn patients undergoing skin-grafting procedures.

OBJECTIVE: To determine if topical administration of local anesthesia, applied to fresh skin-harvest sites, reduces pain and analgesic requirements after surgery. SUMMARY BACKGROUND DATA: Nonopioid treatments for pain after therapeutic procedures on patients with burns have become popular because of the side effects associated with narcotics. The topical administration of local anesthesia originally offered little advantage because of poor epidermal penetration. METHODS: This study compares 2% lidocaine with 0.5% bupivacaine or saline, topically applied after skin harvest, to determine what effect this may have on pain and narcotic use. Sixty patients with partial- or full-thickness burns to approximately 10% to 15% of their body were randomly divided into three groups: group 1 received normal saline, group 2 had 0.5% bupivacaine, and group 3 had 2% lidocaine sprayed onto areas immediately after skin harvest. Blood samples were subsequently obtained to measure concentrations of the local anesthetic. Hemodynamic variables after surgery, wake-up times, emetic symptoms, pain, and narcotic use were compared. RESULTS: Higher heart rates were noted in the placebo group than in those receiving lidocaine or bupivacaine. No differences were noted in recovery from anesthesia or emetic symptoms. Pain scores were lower and 24-hour narcotic use was less in patients who received lidocaine. Plasma lidocaine levels were greater than bupivacaine at all time points measured. CONCLUSIONS: Topical lidocaine applied to skin-harvest sites produced an analgesic effect that reduced narcotic requirements compared with patients who received bupivacaine or placebo. Local anesthetic solutions aerosolized onto skin-harvest sites did not affect healing or produce toxic blood concentrations.

Adolescent↗

Tetrahydrocannabinol (THC) interferes with conditioned retching in Suncus murinus: an animal model of anticipatory nausea and vomiting (ANV).

Little is understood about effective countermeasures to the expression of anticipatory nausea and vomiting (ANV) in chemotherapy patients. We present a model of ANV based on the emetic reactions of the Suncus murinus (musk shrew). Following two pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with THC at a dose that did not suppress general activity. This provides the first experimental evidence in support of anecdotal reports that THC suppresses ANV.

Animals↗

Emerging differences between 5-HT3 receptor antagonists.

A brief review is presented of some recently described 5-HT3 receptor antagonists. These antagonists are primarily targeted for use as anti-emetics. However, evidence is emerging that there are differences in their basic pharmacology. This evidence is reviewed in terms of the selectivity of the antagonists in binding studies and also of their efficacy in emesis and gastric emptying. The possibility that these differences may translate into meaningful clinical differences between the available 5-HT3 receptor antagonists in their use as anti-emetics is also discussed.

Animals↗

Ondansetron in the control of chemotherapy-induced and radiotherapy-induced emesis in children with malignancies.

The management of chemotherapy-induced nausea and emesis presents a major problem in children with cancer. The anti-emetic properties of the 5-HT3 receptor antagonist ondansetron are well documented in adults receiving cytotoxic chemotherapy. Experience in the treatment of children is still limited. Here we present a review of the literature on the anti-emetic treatment with ondansetron in children. Moreover, we provide recommendations on the use of ondansetron during anti-neoplastic chemotherapy and radiotherapy in pediatric oncology.

Adolescent↗

Clinical studies to assess the economic impact of new therapies: pragmatic approaches to measuring costs.

Pragmatic clinical trials using unselected patients in normal clinical situations are more appropriate for the economic assessment of new drugs. However, standard clinical studies that do not reflect current practice are useful and at present the only source of information. Anti-emetic drug studies using granisetron and ondansetron have demonstrated that the overall economic impact of these drugs is equivalent to standard therapies such as metoclopramide. Thus, an efficient anti-emetic drug with less frequent dosing, using a simplified dosage regimen and producing a reduction in anticipatory nausea and vomiting and in nursing time, may result in an overall reduction in cost. Decisions made purely on the basis of drug costs may be misleading and promote inefficient use of health resources.

Antiemetics↗

Cost effectiveness of 5-hydroxytryptamine3 receptor antagonists: a retrospective comparison of ondansetron and granisetron.

As clinical and economic analyses to date have shown clear benefits of using the new 5-hydroxytryptamine3 receptor antagonists (5-HT3RAs) over traditional antiemetics, the choice between them may necessitate the assessment of comparative cost-effectiveness. This paper presents the results of an assessment of the relative cost-effectiveness of two current 5-HT3RAs: ondansetron and granisetron. The analysis was based on a retrospective assessment of the cost and effectiveness (defined as no vomiting and no worse than mild nausea) of these new antiemetics. Efficacy data were based on the results of two recently published directly comparative clinical studies of ondansetron versus granisetron in the treatment of chemotherapy-induced emesis following both single-dose and fractionated chemotherapy. The cost of treatment was derived by combining clinical data from these studies with manufacturers' drug prices, and published costs of drug administration and emetic episodes. Costs for inpatient stay and side-effects were assumed to be equal across both treatment alternatives. The results were expressed in terms of the total cost per patient of emetic treatment and the cost per well-controlled patient. On this basis, granisetron was found to be more than 50% more cost-effective than ondansetron. This result was robust to variation in key assumptions concerning efficacy and cost, although ondansetron would become the more cost-effective if the dose was reduced to one 8 mg i.v., with no concomitant loss of efficacy.

Antineoplastic Agents↗

Antiemetic treatment with two different doses of methylprednisolone in breast cancer patients: a double-blind randomized cross-over study with evaluation of efficacy parameters.

This randomized double-blind cross-over study followed a previous one which showed an antiemetic efficacy from methylprednisolone (MP) 250 mg superior to placebo. The present study compared MP 40 mg with 250 mg in breast cancer patients treated with non-cisplatin chemotherapy. Preference after course II was the determining parameter. Participation in two courses was compulsory for evaluation, participation in four courses was optional. Interim analyses were performed after each 12 patients to a maximum of 60 patients. As there was no significant difference in preference in 60 patients the study was closed. Patients treated with the CEF regimen, patients who requested rescue antiemetics and patients completing four study courses had a better effect from high-dose MP reflected in preference and other parameters. Global assessments, measurement of emetic volumes and the visual analog scale for nausea gave a fair coherence with patients' preference. The numbers of emetic episodes and observer registered nausea were of no value. The stability of preference and other parameters after course II and IV, respectively, was low. The present study did not prove superiority from high-dose MP. This hypothesis must be tested in patients more severely bothered by emesis after chemotherapy. These results show the complexity of evaluation of antiemetic effect and demonstrate the dependency of a given result on the parameter used.

Adult↗

Prospective study of the clinical symptoms of therapeutic whole body irradiation.

Thirty-one selected patients with various haematological malignancies who received a 10 Gy-4 h total body irradiation (TBI) at the Institut Gustave Roussy 24 h before high dose cyclophosphamide for bone marrow transplantation, were prospectively evaluated for gastrointestinal symptoms, body temperature, consciousness, headache, xerostomia, parotiditis, ocular symptoms, blood pressure, and respiratory and cutaneous signs for 24 h. In spite of prophylactic administration of various anti-emetic agents, 90% of the patients experienced nausea and 80% experienced vomiting. An almost constant body temperature peak--up to 40.8 degrees C--was registered 6 h after the start of irradiation. No drowsiness was reported since the introduction of the new anti-emetic agent Ondansetron. Nearly half the patients (42%) complained of headache. The proportion of patients experiencing early (during TBI) xerostomia was 61%. 74% of patients complained of parotiditis in the first 24 h. Although this low dose rate whole body irradiation is not likely to be exactly replicated in many accidental human exposures, the incidence rate and the time-course of the observed prodromal phase symptoms may prove helpful for early triage in the case of accidental irradiation.

Adolescent↗

Serotonergic mediation of vomiting.

In the latter part of the 20th century, significant advances have been made in the understanding of the emetic reflex. As a result, there have been major improvements in the treatment of vomiting, particularly that associated with chemo- and radiotherapeutic treatments for neoplastic disease. The 5-HT3 receptor antagonists (ondansetron and granisetron) have been demonstrated to be of benefit in treating the profound emesis observed during cancer treatment. This observation, together with results from pharmacologic and physiologic investigations in both animals and humans, have identified 5-hydroxy-tryptamine (5-HT or serotonin) to be of fundamental importance in the pathogenesis of emesis. 5-HT appears to be released by radiation and chemotherapeutic agents from enterochromaffin cells within the wall of the intestine, and possibly from neurons within the brainstem. Stimulation of 5-HT3 receptors, located centrally in the dorsal medulla of the brainstem and peripherally on vagal afferent terminals in the gastrointestinal tract, appears to play a pivotal role in eliciting emesis. The interaction of 5-HT with non-5-HT3 receptors, particularly 5-HT1A and 5-HT4 receptors, may be important in the emetic reflex. The development of agents that interact with these receptors may offer alternative approaches to the treatment of nausea and vomiting.

Animals↗

Nausea and vomiting in pregnancy: a review.

Throughout pregnancy, women with nausea and vomiting in early pregnancy showed a different metabolic pattern compared to asymptomatic pregnancies. Women suffering from nausea and vomiting seem to have a low "functional reserve" of their liver capacity and could tentatively be described as hypersensitive to estrogens or their metabolites, e.g., catecholestrogens. These steroids have "emetic" properties, which might be explained by their direct stimulation of area postrema. It is known that estrogens increase the brain's excitability. Another possible mechanism could be by interacting with liver metabolism, resulting in the production of irregular metabolites, which in turn possess "emetic" qualities.

Contraceptives, Oral↗

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Adolescent↗

Customized anesthetic preservation of ictal threshold in electroconvulsive therapy: role of adjunctive remifentanil with etomidate.

We present a case of anesthesia for electroconvulsive (ECT) therapy that was complicated by emetic sensitivity to etomidate, fragile ictal threshold, and mild pseudocholinesterase deficiency. The anesthetic was designed in this patient taking all his issues in consideration. The mild pseudocholinesterase deficiency necessitated a (50-75%) reduction in succinylcholine dosage, careful monitoring of the train of four, and postictal amnestic coverage to prevent paralysis upon waking. The significant emetic response to etomidate prompted substitution to propofol and preemptive ondansetron. Propofol significantly raised the ictal threshold but significantly reduced the postprocedural emesis. Eventually, this clinical challenge was resolved with adjunctive use of low-dose etomidate and remifentanil. This combination preserved the ictal parameters, providing patient comfort, good clinical response, and therapeutic efficacy. Although seizure duration and quality often are restored with hyperventilation and caffeine, this case necessitated a return to etomidate for the restoration of satisfactory ictal parameters. Although this effect of remifentanil has been described with methohexital, and etomidate with alfentanil, to the best of our knowledge, this is the first reported case of adjunctive remifentanil with etomidate for preserving ictal threshold. The outpatient course of ECT was thus completed with all psychiatric and anesthetic goals satisfied: adequate seizure quality and duration, no paralysis upon waking, no post-ECT nausea and vomiting, and patient satisfaction. Anesthesiologists should be aware of factors influencing the seizure duration and, keeping in mind the coexisting medical conditions of the patient, adjustments should be made to get the best possible outcome.

Adult↗

Prevention of nausea and vomiting after day case gynaecological laparoscopy. A comparison of ondansetron, droperidol, metoclopramide and placebo.

We have compared the efficacy of ondansetron, metoclopramide, droperidol and placebo in the prevention of postoperative nausea and vomiting in 118 day stay patients undergoing laparoscopic gynaecological procedures. All received a standardised general anaesthetic of fentanyl, propofol, nitrous oxide in oxygen and isoflurane. Three to five min before induction of anaesthesia, patients were allocated to receive ondansetron 4 mg, metoclopramide 10 mg, droperidol 1 mg or placebo in a randomised, double-blind manner. Visual analogue scores for nausea, the incidence of emetic episodes, and analgesic and antiemetic consumption were recorded for 48 h postoperatively. The scores for nausea were significantly lower in the ondansetron group (p < 0.01) compared with the other three groups at 1, 2 and 4 h after operation; thereafter there was no difference. The incidence of emesis was lower (p = 0.063) and time to first oral fluids was shorter (p < 0.05) in the ondansetron group. Oral analgesic requirements were significantly greater in the ondansetron group over the 48 h study period. Two patients, one each in the placebo and metoclopramide groups, had to remain in hospital overnight because of persistent emetic symptoms.

Adult↗

Antiemetic efficacy of prophylactic ondansetron in laparoscopic cholecystectomy. A randomised, double-blind, placebo-controlled trial.

The antiemetic efficacy of ondansetron given prophylactically was investigated in a randomised, double-blind, placebo-controlled trial of 63 patients undergoing laparoscopic cholecystectomy. The patients received intravenously prior to anaesthesia either ondansetron 4 mg or placebo. The same standardised general anaesthetic technique was used. Nausea, emetic episodes and the need for rescue medication were recorded for 24 h postoperatively. Nausea was experienced by 64% of the patients in the ondansetron group and 56% in the placebo group, and emetic episodes occurred in 45% and 50% of the patients in the two groups, respectively. The proportions of patients given rescue antiemetic medication were 45% and 44%, respectively. No clinically important adverse events were observed. In conclusion, ondansetron given prior to anaesthesia in a dosage of 4 mg did not prevent postoperative nausea and vomiting after laparoscopic cholecystectomy.

Adult↗

Comparison of surgical site and patient's history with a simplified risk score for the prediction of postoperative nausea and vomiting.

Although site of surgery and previous occurrence of postoperative nausea and vomiting are often used to decide whether prophylactic anti-emetic drugs are indicated, the value of these predictors is unclear. We compared these two risk factors against a simplified four-factor risk score. We analysed data from 1566 adult inpatients who received balanced anaesthesia without prophylactic anti-emetics. Sensitivity, specificity, predictive value and area under the receiver operating characteristic curve were used to quantify predictive properties. Nausea and vomiting occurred in 600 (38.3%) patients within 24 h. Sensitivity and specificity were, respectively, 47% and 59% for surgical site; 47% and 70% for history of postoperative nausea and vomiting; and 58% and 70% for risk score with three or more factors. The area under the curve for surgical site was 0.53 (95% CI 0.50-0.56); that for patient's history was 0.58 (95% CI 0.56-0.61) while for risk score it was 0.68 (95% CI 0.66-0.71; P < 0.001). Prediction using surgical site or patient's history alone was poor while the simplified risk score provided clinically useful sensitivity and specificity.

Adult↗

A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting.

We conducted a randomised double-blinded study of 960 women undergoing day-case surgery to determine whether combination anti-emetic therapy of granisetron and cyclizine was more effective at decreasing the incidence of postoperative nausea and vomiting than these agents used alone. The women were randomly allocated to three groups to receive intravenous granisetron 1 mg, cyclizine 50 mg or both before induction of general anaesthesia. The incidence of postoperative nausea and vomiting was 77/322 (24%) in the granisetron group, 73/316 (23%) in the cyclizine group and 53/322 (17%) in those women given both drugs (p = 0.04). There was no difference in the requirement for rescue anti-emetic drugs. There were no differences in the anaesthetic techniques used in the three groups. We conclude that the risk of postoperative nausea and vomiting is less with cyclizine and granisetron given together than with either given alone.

Adult↗

Midazolam vs ondansetron for preventing postoperative nausea and vomiting: a randomised controlled trial.

We compared the prophylactic anti-emetic efficacy of midazolam and ondansetron in 90 patients scheduled for minor gynaecological (hysteroscopy) or urological (ureteroscopy) procedures planned to last 1-2 h under sevoflurane anaesthesia with spontaneous ventilation of the lungs via a laryngeal mask airway. Midazolam 2 mg or ondansetron 4 mg were administered intravenously 30 min before the end of surgery. The proportions of patients who experienced postoperative nausea and vomiting in the first 24 h (30% and 27% for the midazolam and ondansetron groups, respectively) were similar in the two groups. The incidence of postoperative nausea and vomiting was significantly smaller in both groups than predicted according to the patients' underlying risks (midazolam group: p = 0.018; ondansetron group: p = 0.017). There were no significant differences in average sedation scores or pain scores. Treatment using ondansetron for anti-emetic prophylaxis did not provide a superior benefit compared to midazolam in the present study.

Adjuvants, Anesthesia↗

Responses of plasma oxytocin and arginine vasopressin to nausea induced by apomorphine and ipecacuanha.

Apomorphine, a centrally-acting emetic, was administered subcutaneously (50 micrograms/kg) to nine normal subjects (four male, five female; aged 22-36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24-49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9.5 +/- 0.9 min which was followed by a large increase in plasma arginine vasopressin (AVP) concentration (from 0.9 +/- 0.2 pmol/l to 249 +/- 104 pmol/l at 15 min after the onset of symptoms; mean +/- SEM, P less than 0.01). There was a small but significant increase in plasma oxytocin (OXT) concentration (from 1.6 +/- 0.4 pmol/l to 6.2 +/- 3.4 pmol/l; P less than 0.05). Mean arterial pressure (MAP) fell slightly (from 87 +/- 1.9 mm Hg to 71 +/- 4.4 mm Hg; P less than 0.05) 15 min after the onset of nausea; there was no change in blood haematocrit or plasma osmolality and sodium concentration. In the DI patients apomorphine produced nausea (with vomiting in three of four) with a latency of 10.0 +/- 1.4 min but failed to cause an increase in either plasma AVP or OXT. In the DI patients the fall in MAP did not reach statistical significance (83 +/- 4 mm Hg to 71 +/- 11 mm Hg); there was also no change in haematocrit, osmolality or sodium concentration. Ipecacuanha, an emetic with both peripheral and central actions, was administered orally to seven normal subjects (three male, four female; aged 22-36 years) six of whom also underwent apomorphine tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗