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Serum levels of dimenhydrinate. Determination by HPLC with UV detection after intake of dimenhydrinate in a coated chewing gum dragee.

HPLC with UV detection allowed to separate dimenhydrinate and three major metabolites (diphenyl-methoxy-ethylamine, diphenyl-methoxy-acetic acid, diphenyl-methoxy-N-methyl-amine) in human serum without extraction procedure. Detection limit was 25 ng per 500 microliter injected sample, the recovery ranged from 70 to 95%. Serum levels of dimenhydrinate were measured in healthy volunteers 15, 30, 60 and 120 min after intake of two commercially available preparations, one of them a dimenhydrinate tablet, the other one a dimenhydrinate containing coated chewing gum dragee (Travel-Gum dragee). The rise of the serum concentration of dimenhydrinate up to 30 min was smaller after intake of the coated chewing gum preparation than after swallowing the tablet. The serum concentrations at 1 or 2 h after the intake of either a tablet or the chewing gum were comparable. The variability of the serum concentrations was considerable with both preparations and seemed to be influenced more by individual factors than by previous food intake.

Administration, Oral↗

[Prophylaxis of postoperative nausea and vomiting (PONV) in children undergoing strabismus surgery. Sevoflurane/N2O plus dimenhydrinate vs.propofol/remifentanil plus dimenhydrinate].

UNLABELLED: BACKGROUND AND STUDY GOALS: Strabismus surgery in children is frequently associated with a very high incidence of postoperative nausea and vomiting (PONV). In this study we investigated, whether TIVA is superior to inhalation anaesthesia concerning PONV when a prophylaxis using dimenhydrinate (diphenhydramine chlorotheophyllate) is administered in both groups. METHODS: 110 patients (3-10 years) were prospectively and randomly allocated to one of the following groups: Group TD (TIVA/dimenhydrinate; n= 55): anaesthesia was induced and maintained using remifentanil and propofol in common clinical dosages. Patients were ventilated with 30% O(2) in air. Group VD (Volatile/ dimenhydrinate; n= 55): anaesthesia was induced and maintained with sevoflurane in common clinical concentrations together with N(2)O in 30% O(2). All patients received dimenhydrinate 1 mg.kg(-1) i.v. after induction. PONV was recorded within the first 24 h postoperatively. The chi-square test and a multivariate analysis were used for statistical analysis. RESULTS: 52 patients of group TD and 54 of group VD were analysed. There was a trend in the incidence of postoperative nausea (PN): group TD 17%, 95% CI: 8-30%) compared to group VD 31%, 95% CI: 20-46%), p = 0.09. No difference was seen for PV and PONV: 21% (95% CI: 11-35%) in group TD vs. 35% (95% CI: 23-49%) in group VD, p = 0.109. These non-significant results can be easily attributed to the lack of power about 30%) of this study. According to the results of the multivariate analysis volatile anaesthesia was identified as an independent risk factor for PONV (OR: 2.92, 95% CI: 1.02-8.36). Other variables that were found to be an independent risk factor included history of PONV (OR: 8.19, 95% CI: 1.84-36.43), surgery lasting longer than 30 min (OR: 5.89, 95% CI: 1.82-19.82) and "Faden-operations" (retroequatorial myopexy) (OR: 5.48, 95% CI: 1.74-17.21). CONCLUSIONS: TD only showed a trend to lower PN incidences and no differences as for PV and PONV incidences, most likely due to a lack of power of this study. However, according to the results of the multivariate analysis, inhalation anaesthesia was shown to be an independent risk factor for PONV, as were history of PONV, surgery >30 min and "Faden-operations".

Anesthesia, Inhalation↗

Diphenhydramine and dimenhydrinate poisoning: an evidence-based consensus guideline for out-of-hospital management.

In 2003, there were 28,092 human exposures to diphenhydramine reported to poison centers in the US. A related drug, dimenhydrinate, is a less frequent cause of poisonings. Between January 2000 and June 2004, there were 2,534 reported dimenhydrinate ingestions in children less than 6 years of age. An evidence-based expert consensus process was used to create this guideline. Relevant articles were abstracted by a trained physician researcher. The first draft was created by the primary author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with a suspected ingestion of diphenhydramine or dimenhydrinate, or a dermal exposure to diphenhydramine. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. The panel's recommendations for dermal or oral exposures to diphenhydramine or oral exposures to dimenhydrinate follow. The grade of recommendation is in parentheses: 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) In patients without evidence of self-harm, abuse, or malicious intent, poison center personnel should elicit additional information including the time of the ingestion or dermal exposure, determination of the precise dose ingested, and the presence of co-ingestants (Grade D). 3) Patients experiencing any changes in behavior other than mild drowsiness or mild stimulation should be referred to an emergency department. Examples of moderate to severe symptoms that warrant referral include agitation, staring spells, inconsolable crying, hallucinations, abnormal muscle movements, loss of consciousness, seizures, or respiratory depression (Grade D). 4) For patients referred to the emergency department, transportation via ambulance should be considered based on several factors including the condition of the patient and the length of time it will take the patient to arrive at the emergency department (Grade D). 5) If the patient has no symptoms, and more than 4 hours have elapsed between the time of diphenhydramine ingestion and the call to the poison center, referral to an emergency department is not recommended. For dermal exposures to diphenhydramine, if the patient has no symptoms and it has been more than 8 hours since the diphenhydramine was thoroughly removed from the skin, referral to an emergency department is not recommended (Grade D). 6) Patients with acute ingestions of less than a toxic dose of diphenhydramine, or chronic exposures to diphenhydramine and no or mild symptoms, can be observed at home with instructions to call the poison center back if symptoms develop or worsen. The poison center should consider making a follow-up call at approximately 4 hours after ingestion (Grade D). 7) Children less than 6 years of age who ingest at least 7.5 mg/kg of diphenhydramine should be referred to an emergency department (Grade D). 8) Patients 6 years of age and older who ingest at least 7.5 mg/kg or 300 mg of diphenhydramine (whichever is less), should be referred to an emergency department (Grade D). 9) If the patient has no symptoms, and more than 6 hours have elapsed between the time of dimenhydrinate ingestion and the call to the poison center, referral to an emergency department is not recommended (Grade D). 10) Patients with acute ingestions of less than a toxic dose of dimenhydrinate, or chronic exposures to dimenhydrinate and no or mild symptoms, can be observed at home with instructions to call the poison center back if symptoms develop or worsen. The poison center should consider making a follow-up call at approximately 6 hours after ingestion (Grade D). 11) Children less than 6 years of age ingesting at least 7.5 mg/kg of dimenhydrinate should be referred to an emergency department (Grade D). 12) Patients 6 years of age and older ingesting at least 7.5 mg/kg or 300 mg of dimenhydrinate (whichever is less), should be referred to an emergency department for evaluation (Grade D). 13) Following oral exposures of diphenhydramine or dimenhydrinate, do not induce emesis. Because of the potential for diphenhydramine or dimenhydrinate to cause loss of consciousness or seizures, activated charcoal should not be administered en route to an emergency department (Grade D). 14) For chronic dermal exposures of diphenhydramine, skin decontamination (with water or soap and water) should be attempted prior to transporting a patient to an emergency department unless moderate to severe symptoms are already present. In this circumstance, transportation should not be delayed, and EMS personnel should attempt skin decontamination en route to the emergency department (Grade D). 15) Intravenous sodium bicarbonate may be administered by EMS personnel if QRS widening (QRS >0.10 msec) is present and if authorized by EMS medical direction (Grade D). 16) Physostigmine should be reserved for administration in a hospital (Grade D). 17) Benzodiazepines may be administered by EMS personnel if agitation or seizures are present, and if authorized by EMS medical direction (Grade D).

Age Factors↗

Treatment of vertigo due to acute unilateral vestibular loss with a fixed combination of cinnarizine and dimenhydrinate: a double-blind, randomized, parallel-group clinical study.

BACKGROUND: Acute unilateral vestibular loss is a balance disorder that is accompanied by vertigo symptoms and concomitant vegetative symptoms, including nausea and vomiting. Patients are frequently confined to bed rest but may continue to experience vertigo symptoms. A well-established antivertiginous therapy consisting of cinnarizine and dimenhydrinate at low doses may offer rapid relief of acute vertigo symptoms due to acute vestibular loss, without inhibiting physiological compensation processes. OBJECTIVE: The purpose of this study was to compare the clinical efficacy and tolerability of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg versus monotherapy with its respective components in the treatment of acute vertigo symptoms due to acute unilateral vestibular loss. METHODS: In this prospective, single-center, randomized, double-blind, parallel-group clinical study, 50 patients with acute vestibular vertigo were randomly assigned to receive 4 weeks of treatment (1 tablet 3 times daily) with a fixed combination of 20 mg cinnarizine and 40 mg dimenhydrinate, 20 mg cinnarizine alone, or 40 mg dimenhydrinate alone. All patients received a 15% mannitol infusion as standard therapy during the first 6 days of treatment. Efficacy was determined by the patients' assessments of vertigo symptoms after 1 and 4 weeks of treatment using a verbal rating scale (vertigo score) and by vestibulo-ocular and vestibulospinal tests. The primary efficacy criterion was defined as the relief of vertigo symptoms after 1 week of treatment. RESULTS: After 1 week of treatment, the fixed combination was significantly more effective than 20 mg cinnarizine (P < 0.001) and 40 mg dimenhydrinate (P < 0.01). After 4 weeks, the fixed combination was still significantly more effective than cinnarizine in reducing vertigo symptoms (P < 0.01) and significantly more effective than dimenhydrinate in improving the patients' balance while standing (P < 0.05). The tolerability of the fixed combination was rated good or very good by 100% of the patients (cinnarizine alone, 82.4%; dimenhydrinate alone, 94.4%). No serious adverse events occurred. Four patients in the fixed combination and the cinnarizine groups, and 6 patients in the dimenhydrinate group reported nonserious adverse events. CONCLUSIONS: The results of this study suggest a distinct benefit in using a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg versus the respective monotherapies in this population of patients with acute vestibular vertigo.

Acute Disease↗

Reduction of postoperative nausea and vomiting by dimenhydrinate suppositories after strabismus surgery in children.

UNLABELLED: Although dimenhydrinate has been used for treatment and prevention of postoperative nausea and vomiting (PONV) since the fifties, there have been few controlled studies about its efficacy. We performed a double-blinded study of 301 children aged 4 to 10 yr who underwent strabismus surgery. Preanesthetic medication with midazolam (0.5 mg/kg) as well as application of either dimenhydrinate suppositories or a placebo preparation was performed 30 min before the induction of anesthesia. Anesthesia was induced with thiopentone (5-10 mg/kg) and vecuronium (0.1 mg/kg) and maintained with halothane (1%-2%) in N(2)O/O(2) (65%/35%). The incidence of PONV, requirements for rescue dimenhydrinate, and time to recovery were recorded. The overall incidence of PONV was 60.1% in the placebo group and 30.7% in the dimenhydrinate group. In the dimenhydrinate group, children had to be observed in the recovery room significantly longer than those in the placebo group. Children having received dimenhydrinate were discharged from the recovery room with lower arousal scores. We conclude that the rectal administration of dimenhydrinate is effective for the prevention of PONV, although the sedative effect may require longer postoperative monitoring. IMPLICATIONS: We performed a double-blinded, randomized study to investigate the effects of prophylactic rectal dimenhydrinate application on postoperative nausea and vomiting in children undergoing strabismus surgery. In comparison with placebo, dimenhydrinate reduced the incidence of postoperative vomiting from 60.1% to 30.7%.

Anesthesia, Inhalation↗

Dimenhydrinate for prevention of post-operative nausea and vomiting in female in-patients.

Dimenhydrinate is an inexpensive antihistaminic drug, that is frequently used as an anti-emetic during anaesthesia. The popularity of the drug is contrasted by the lack of modern studies concerning its efficacy in reducing the incidence of post-operative nausea and vomiting. Thus, dimenhydrinate was compared with placebo in this prospective, randomized, double-blind study. One hundred and thirty-three female in-patients were studied. They were stratified according to the type of surgery (laparoscopic cholecystectomy, thyroid resection or knee arthroscopy) to ensure an homogeneous distribution in both groups. General anaesthesia was induced with etomidate, fentanyl, vecuronium and maintained with enflurane in N2O/O2. Neuromuscular block was reversed with pyridostigmine/atropine. Patients in the dimenhydrinate group (n = 67) received 62 mg dimenhydrinate intravenously after induction of anaesthesia. Placebo patients (n = 66) received saline. Administration of dimenhydrinate (and placebo) was repeated three times during the 48-h study to mitigate the short half-life of the drug. Post-operative analgesia and anti-emetic rescue medication was standardized. Episodes of vomiting, retching and the need for additional anti-emetics were recorded. Nausea was assessed using a 10-cm visual analogue scale. Post-operative nausea and vomiting was rated as 'none', 'mild', 'moderate' and 'severe' using a fixed scoring algorithm. There were no differences between the two groups with regard to biometric data, type of surgery and distribution of risk factors for developing post-operative nausea and vomiting. In the dimenhydrinate group, more patients remained completely free from post-operative nausea and vomiting compared with placebo (dimenhydrinate: 38.8%; placebo: 15.1%; P = 0.004). The incidence of severe post-operative nausea and vomiting was also reduced from 39.4% to 14.9%. No relevant side effects were observed. Intra-operative dimenhydrinate, followed by three further administrations after surgery, reduces the incidence and the severity of post-operative nausea and vomiting without side effects. However, there still remained an unacceptable high number of patients who were not prevented completely from experiencing post-operative nausea and vomiting.

Adult↗

Intravenous Lorazepam versus dimenhydrinate for treatment of vertigo in the emergency department: a randomized clinical trial.

STUDY OBJECTIVE: To determine whether lorazepam is more effective than dimenhydrinate in relieving the symptom of vertigo in the emergency department setting. METHODS: A prospective, randomized, double-blind trial of intravenous lorazepam versus dimenhydrinate therapy was conducted in the ED of a county-owned, university-affiliated hospital. All adult patients who presented between January 24, 1998, and May 23, 1999, with the symptom of vertigo were eligible for inclusion. The intervention was varying the intravenous treatment between lorazepam, 2 mg, and dimenhydrinate, 50 mg. All patients received intravenous infusion of Ringer's lactate solution at a rate of 100 mL/h. Adequacy of randomization to the 2 treatment groups was assessed by comparing the patients' relevant baseline history, physical examination, and symptoms. The predetermined primary outcome measurement was the patient's sensation of "vertigo with ambulation" 1 and 2 hours after treatment. Secondary outcome measurements included vertigo while lying, sitting, and turning the head, ability to ambulate as judged by the enrolling physician, and sensation of nausea and drowsiness 1 and 2 hours after treatment, and whether the patient was "ready to go home" per patient report or physician assessment 2 hours after treatment. All patient symptoms were reported on 10-point scales. Outcome measurements were compared between the 2 treatment groups with a 2-way repeated-measures analysis of variance, Student's t test, Mann-Whitney U, and chi(2) test as appropriate. RESULTS: Ten patients refused entry into the study, 16 were excluded, and 74 were enrolled, treated, and included in the analysis. One enrolled patient had evidence of vertigo of central origin. The pretreatment values of vertigo with ambulation were strongly correlated with the patient's ability to ambulate (P <.001), suggesting good internal validity. The patients randomly assigned to the lorazepam group were sicker based on their pretreatment symptoms and ability to ambulate, and this may have biased the study results. The patients' symptom of "vertigo with ambulation" decreased 1.5 units more (95% confidence interval [CI] 0 to 3.0) on average on a 10-point scale 2 hours after treatment in the dimenhydrinate group. All other measures of vertigo also decreased more in the dimenhydrinate group, although the differences were not statistically significant. At 2 hours after treatment, the patients' ability to ambulate was better in the dimenhydrinate group (P <.001), and 17% (95% CI -2 to 36) more patients in this group were "ready to go home." Patients in the lorazepam group experienced a 1.8-unit (95% CI 0.2 to 3.4) greater increase in drowsiness 2 hours after treatment. CONCLUSION: Our results suggest that dimenhydrinate was more effective in relieving vertigo and less sedating than lorazepam at the intravenous doses administered in this study. Dimenhydrinate appears to be the preferred medicine for patients who present to the ED with vertigo likely to be of peripheral origin.

Adult↗

The search for cost-effective prevention of postoperative nausea and vomiting in the child undergoing reconstructive burn surgery: ondansetron versus dimenhydrinate.

Postoperative nausea and vomiting (PONV) is a common and unpleasant problem for children with burns who are undergoing reconstructive burn surgery. Ondansetron and dimenhydrinate have been found to be effective for the prevention of PONV in other patient populations, but they have not been directly compared in the pediatric population. A prospective, randomized, double-blind, placebo-controlled comparison of ondansetron and dimenhydrinate was performed. One hundred patients with a mean age of 11.8 years who were undergoing reconstructive burn surgery with general anesthesia were randomly assigned to receive either a placebo, 0.1 mg/kg of ondansetron, or 0.5 mg/kg of dimenhydrinate. The 3 groups were well matched for all demographic and procedural variables. The study drugs were given twice, first at the end of surgery and again 4 hours later, to ensure adequate blood levels during the 8-hour study period. Postoperatively, on the basis of the presence and amount of PONV experienced, all patients were assigned a PONV score by a blinded investigator. Statistically significant reductions in the incidence of PONV in the patients who received ondansetron or dimenhydrinate were found, as compared with the results of patients who received placebo. Postoperative vomiting was reduced from 61% in the placebo group to 29% and 40% in the ondansetron and dimenhydrinate groups, respectively, and PONV was similarly reduced from 69% to 47% and 40%, respectively. The differences between ondansetron and dimenhydrinate were not significant. The average cost to our pharmacy for the prescribed dose of ondansetron was $19.34; the cost for dimenhydrinate was $0.90. In this patient population, dimenhydrinate was as effective as ondansetron for the prevention of PONV and postoperative vomiting, and it was much less expensive.

Adolescent↗

Prophylaxis of postoperative nausea and vomiting with oral, long-acting dimenhydrinate in gynecologic outpatient laparoscopy.

UNLABELLED: Dimenhydrinate is an inexpensive antiemetic with few side effects available as an oral, long-acting (LA) formulation (Gravol L/A) containing 25 mg of immediate and 50 mg of sustained release drug. We designed this double-blind comparison trial to assess the efficacy of dimenhydrinate LA versus droperidol alone and the combination for prophylaxis of nausea, vomiting, and retching in outpatient gynecologic laparoscopy. One-hundred-forty-one women were randomized into 3 groups: 1) droperidol (placebo capsule preoperatively and IV droperidol 0.625 mg before induction), 2) dimenhydrinate LA preoperatively and IV placebo before induction, or 3) combination. Information regarding nausea, vomiting, retching, pain, and sedation was recorded in the postanesthesia care unit (PACU) and collected by telephone for the presence of symptoms: on arrival home; at bedtime; upon arising, and at lunchtime the following day. The overall incidence of complete treatment failure (rescue medication in PACU or nausea, vomiting, or retching at any time point) was 28 of 46 (61%), 28 of 48 (58%), and 22 of 47 (47%); and for treatment failure vomiting (rescue medication in PACU or vomiting or retching at any time point) was 16 of 46 (35%), 11 of 48 (23%), and 5 of 47 (11%), for the droperidol, dimenhydrinate, and combination groups, respectively (P = 0.007 for droperidol versus combination). There were no differences in sedation or pain. Preoperative administration of an oral dose of LA dimenhydrinate in combination with droperidol when compared with droperidol alone effectively reduced the incidence of vomiting but not nausea in women undergoing elective outpatient gynecologic laparoscopy. IMPLICATIONS: Dimenhydrinate is an inexpensive antiemetic with few side effects available as a long-acting oral formulation. Women undergoing outpatient gynecologic laparoscopy were given droperidol, an effective antiemetic, dimenhydrinate alone, or the combination of the two drugs. Dimenhydrinate plus droperidol significantly reduced the overall incidence of vomiting, but not nausea, when compared with droperidol alone.

Administration, Oral↗

Effects of dimenhydrinate on gastric tachyarrhythmia and symptoms of vection-induced motion sickness.

BACKGROUND: Previous research in our laboratory has shown that symptoms of motion sickness are accompanied by the loss of normal 3 cpm activity and the development of tachyarrhythmia in the electrogastrogram (EGG). HYPOTHESIS: We hypothesized that dimenhydrinate would prevent the development of gastric tachyarrhythmia and reduce symptoms of motion sickness. METHODS: Twenty health volunteers were tested in a counter-balanced, within-subject, double-blind design. Subjects were exposed to a rotating optokinetic drum to induce vection after receiving either dimenhydrinate (100 mg) or a placebo on two separate occasions. EGG's were recorded immediately before ingestion of capsules, 1 h after ingestion, and during rotation. Motion sickness symptom reports (SSMS) were obtained prior to and during rotation. RESULTS: The average SSMS score was 5.9 points higher after placebo administration than after dimenhydrinate administration (t[19] = 4.87, P < 0.001). Significantly more subjects requested early termination of the rotating drum due to severe symptoms after placebo administration than after dimenhydrinate administration (McNemar's chi 2[1] = 6.00, p < 0.05). Drowsiness reports were significantly higher after dimenhydrinate administration than after placebo administration (t[19] = 2.65, p < 0.05). Analysis of EGG's showed a significant decrease in normal 3 cpm and tachyarrhythmic activity after dimenhydrinate, but no change after placebo (SR[19] = 53, p < 0.02 and SR[19] = 68, p < 0.01 respectively). During drum rotation gastric tachyarrhythmias increased significantly in the placebo condition (SR[18] = -0.61.5, p < 0.01), but not in the dimenhydrinate condition. EGG's were not significantly different between conditions. CONCLUSIONS: We conclude that dimenhydrinate reduced motion sickness symptoms at least in part by depressing central nervous system activity and possibly by suppressing abnormal gastric myoelectric activity.

Adolescent↗

Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate.

Adolescent↗

Droperidol and dimenhydrinate alone or in combination for the prevention of post-operative nausea and vomiting after nasal surgery in male patients.

Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively, but there are no studies on the combination of both drugs for prevention of post-operative nausea and vomiting. One hundred and forty male hospitalized patients undergoing nasal surgery were randomized to receive one of four anti-emetic regimes: placebo, dimenhydrinate (1 mg kg-1), droperidol (15 micrograms kg-1), or the combination of both drugs (droperidol 15 micrograms kg-1 + dimenhydrinate 1 mg kg-1) administered after induction of anaesthesia. Patients in the dimenhydrinate-group and the combination-group received a second dose of dimenhydrinate 6 h after the first administration to mitigate the short half-life of the drug. For general anaesthesia a standardized technique, including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil, was used. Post-operative analgesia and anti-emetic rescue medication were standardized. Episodes of vomiting, retching, nausea, and the need for additional anti-emetics were recorded for 24 h. The main endpoint of this study was the number of patients who were completely free of post-operative nausea and vomiting (Fisher's Exact Test). Furthermore, the severity of post-operative nausea and vomiting was analysed using a standardized scoring algorithm. The incidence of patients completely free of post-operative nausea and vomiting was 62.9% in the placebo-group, 77.1% in the dimenhydrinate-group (P = 0.21), and 82.9% in the droperidol-group (P = 0.07). This increased to 94.3% in the combination-group (P = 0.0015). In all three treatment groups the severity of post-operative nausea and vomiting was reduced significantly compared with placebo treatment (P = 0.0003). The incidence of side effects was similar in the four groups. Dimenhydrinate was ineffective in reducing the incidence of post-operative nausea and vomiting and droperidol only reduced the severity of post-operative nausea and vomiting. However, the combination of both drugs significantly reduces the incidence of post-operative nausea and vomiting when compared with placebo treatment.

Adult↗

The effects of dimenhydrinate, cinnarizine and transdermal scopolamine on performance.

We assessed the influence of dimenhydrinate, cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks. The effect of single doses of dimenhydrinate, 100 mg, cinnarizine, 50 mg, and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind, placebo-controlled, randomized, crossover design in three separate studies. A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment. Dimenhydrinate significantly impaired decision reaction time and auditory digit span. Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities. Cinnarizine and transdermal scopolamine did not affect performance abilities. Cinnarizine was free of significant side-effects. Dry mouth was the only significant side-effect of transdermal scopolamine. These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function. Our results suggest that dimenhydrinate, 100 mg, adversely affects psychomotor function, whereas single doses of cinnarizine, 50 mg, and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew.

Administration, Cutaneous↗

Antiemetic efficacy of prophylactic dimenhydrinate (Dramamine) vs ondansetron (Zofran): a randomized, prospective trial inpatients undergoing laparoscopic cholecystectomy.

BACKGROUND: The prophylactic administration of dimenhydrinate (Dramamine) is as effective as the use of ondansetron (Zofran) in preventing postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic cholecystectomy. A prospective double-blind randomized study was performed in a tertiary care referral center. METHODS: For this study, 128 American Society of Anesthesiology (ASA) physical statuses I, II, and III patients were randomly assigned to receive either ondansetron 4 mg intravenously (IV) at $17 per dose (group 1) or dimenhydrinate 50 mg IV at $2.50 per dose (group 2) before induction of anesthesia. The end points evaluated were frequency of PONV, need for rescue antiemetics, need for overnight hospitalization secondary to persistent nausea and vomiting, and frequency PONV 24 h after discharge. RESULTS: Chi-square tests and student's t-test were used to determine the significance of differences among groups. Of the 128 patients enrolled in this study, 20 were excluded: 15 patients received an additional antiemetic preoperative; 4 were converted to open cholecystectomies; and 1 procedure was aborted due to carcinomatosis. Of the 108 remaining participants, 50 received ondansetron (group 1) and 58 received dimenhydrinate (group 2). Both groups were well matched for demographics including gender, ASA class, and history of motion sickness. The need for rescue antiemetics occurred in 34% of group 1 and 29% of Group 2 (p = 0.376), postoperative vomiting in 6% of group 1 and 12% of group 2 (p = 0.228), and postoperative nausea in 42% of group 1 and 34% of group 2 (p = 0.422). One group 1 patient and two group 2 patients required overnight hospitalization for persistent nausea, a difference that was not significant. Rates of PONV 24 h after discharge were similar between groups 1 and 2 (10% vs 14%, p = 0.397 and 2% vs 5%, p = 0.375, respectively). CONCLUSIONS: Prophylactic administration of dimenhydrinate is as effective as the use of ondansetron in preventing PONV in patients undergoing elective laparoscopic cholecystectomy. Dimenhydrinate is the preferred drug because it is less expensive. With more than 500, 000 laparoscopic cholecystectomies performed in the United States each year, the potential drug cost savings from the prophylactic administration of dimenhydrinate instead of ondansetron exceed $7.25 million per year.

Antiemetics↗

Vomiting after adenotonsillectomy in children: a comparison of ondansetron, dimenhydrinate, and placebo.

UNLABELLED: We compared the effectiveness of ondansetron, dimenhydrinate, and placebo for the prevention of postoperative vomiting in children after adenotonsillectomy. In a randomized, placebo-controlled, double-blind study, 74 children, 2-10 yr of age scheduled for adenotonsillectomy as outpatients were given a single i.v. dose of ondansetron (0.1 mg/kg, n = 26), dimenhydrinate (0.5 mg/kg, n = 25), or placebo (saline, n = 23) at induction of anesthesia. The incidence of retching and vomiting (POV) and side effects observed 24 h after surgery were recorded. Demographic data were similar among the three groups. The 24-h incidence of POV was 42%, 79%, and 82% in the ondansetron, dimenhydrinate, and placebo groups, respectively (ondansetron compared with dimenhydrinate [P < 0.02] or placebo [P < 0.01]). The study was stopped after two children vomited large volumes of bloody fluid 9 and 22 h after surgery without previous signs of occult bleeding. Both children had received ondansetron. We conclude that ondansetron is superior to dimenhydrinate or placebo for the prevention of POV after adenotonsillectomy in children. Antiemetics may mask the signs of bleeding after adenotonsillectomy. IMPLICATIONS: I.v. ondansetron (0.1 mg/kg) is more effective than both dimenhydrinate and placebo in preventing vomiting after adenotonsillectomy in healthy children. However, antiemetics may also mask the presence of blood in the stomach by preventing vomiting, and this should be appreciated when adenotonsillectomy is performed on an outpatient basis.

Antiemetics↗

Intramuscular droperidol versus intramuscular dimenhydrinate for the treatment of acute peripheral vertigo in the emergency department: a randomized clinical trial.

OBJECTIVE: The emergency department (ED) treatment of acute peripheral vertigo (APV) has not been well studied. The purpose of this study was to determine the efficacy of intramuscular (IM) droperidol vs IM dimenhydrinate, in the treatment of ED patients with APV. METHODS: The study was a randomized, double-blinded clinical trial, performed at a suburban, teaching ED. A convenience sample of adult patients with symptoms and signs consistent with rigid diagnostic criteria for APV were randomized to one of two treatment groups. Patients more than 65 years of age were excluded to reduce the likelihood of diagnostic misclassification. Demographic and historical features were recorded on a standardized data form. Patients recorded their initial level (t0) of discomfort on a 10-centimeter (cm) visual analog scale (VAS). Treatment group 1 received 2.5 mg droperidol IM, while treatment group 2 received 50 mg dimenhydrinate IM. After 30 minutes (t30), patients again recorded the severity of their symptoms on the VAS. Chi-square, t-tests, and Mann-Whitney were used for statistical comparison as appropriate. All tests were two-tailed, with alpha set at 0.05. Primary outcome parameters were the mean change in VAS score from t0 to t30, and the percentage of patients in each treatment group who felt well enough to go home after t30 without further ED intervention. RESULTS: There were 20 patients in the droperidol group and 20 in the dimenhydrinate group. The two groups were similar with respect to mean age (40 +/- 13 years droperidol vs. 42 +/- 13 years dimenhydrinate; p = 0.6), female sex (60% vs. 50%; p = 0.7), and mean median duration of symptoms [3 (interquartile range 2-12) vs 9 (interquartile range 2-30) hours; p = 0.2]. Mean initial t0 VAS scores were 7.2 +/- 2.3 and 7.8 +/- 1.9 (p = 0.47). Both treatment groups had mean reductions in VAS scores at t30 of 3.3 [95% confidence interval (95% CI) = 2.3 to 4.3]. At t30, 42% of patients in the droperidol group and 45% of patients in the dimenhydrinate group felt well enough to go home without further ED intervention. CONCLUSIONS: The authors found no difference between the therapeutic efficacies of IM droperidol and dimenhydrinate for the treatment of acute peripheral vertigo.

Adult↗

The psychometric and cardiac effects of dimenhydrinate in the hyperbaric environment.

STUDY OBJECTIVES: To examine the psychometric and cardiac effects of dimenhydrinate at 1 and 3 atmospheres (atm) of pressure (0 and 66 feet of sea water, respectively), and to make recommendations about the drug's safety in the diving environment. DESIGN: Double-blind, placebo-controlled, crossover study SETTING: Monoplace hyperbaric chamber of a university hospital. SUBJECTS: Thirty active divers (mean age 38 yrs). INTERVENTIONS: A bank of seven tests was used to assess cognitive function during four different dive combinations: placebo-1 atm, placebo-3 atm, dimenhydrinate-1 atm, and dimenhydrinate-3 atm. MEASUREMENTS AND MAIN RESULTS: Heart rate and cardiac rhythm were recorded during all dives. Repeated-measures multivariate analysis of variance was used to analyze the effects of dimenhydrinate, depth, and drug-depth interaction. Dimenhydrinate resulted in a significant decrease in scores of mental flexibility (trail-making, part B, p<0.05) but had no effect on scores in the six other psychometric tests (p>0.05). It had no effect on mean heart rate (p>0.05), although frequent unifocal ventricular ectopic beats occurred in two subjects after ingestion of the drug. Depth resulted in a significant decrease in verbal memory test scores (p=0.001) and mean heart rate (p<0.001). CONCLUSION: Dimenhydrinate adversely affects mental flexibility. This effect, when added to the adverse effect of depth on memory, may contribute to the dangers of diving.

Aged↗

Diagnostic delay after dimenhydrinate use in vomiting children.

OBJECTIVE: To determine whether the use of dimenhydrinate was associated with delay in the diagnosis and management of treatable illnesses or with direct adverse effects in children with vomiting presenting to an emergency department. DESIGN: Questionnaire survey and review of drug reaction and telephone inquiry records. SETTING: The emergency department of a tertiary care children's hospital and a provincial poison information centre. PATIENTS: The parents of 148 children who presented with vomiting completed the questionnaire. The database at the poison information centre included 474 reports of adverse drug reactions over an 8-year period and 105 reports of telephone inquiries over a 4-year period. MAIN RESULTS: Twenty-one (14%) of 148 children had received dimenhydrinate before arrival at the emergency department. The patients who had received dimenhydrinate were more likely than the others to present more than 12 hours after the onset of vomiting (14 [67%] of 21 v. 43 [34%] of 127, p less than 0.01). The discharge diagnoses for those who had received dimenhydrinate included asthma, pelvic inflammatory disease and urinary tract infection. No clinically important direct adverse reactions to dimenhydrinate were documented. CONCLUSIONS: The use of dimenhydrinate in children with vomiting is associated with a risk of delay in the diagnosis of treatable medical conditions.

Adolescent↗