Extrapyramidal Symptoms, Nausea
Conditions
Keywords
Metoclopramide, Nausea, Akathisia, Emergency department
Brief summary
Metoclopramide is a dopamine antagonist frequently used for the treatment of nausea, vomiting, and migraine headaches in Emergency Departments. However, little research has focused on the optimal dose of metoclopramide for treatment of nausea in the emergency department. We propose a randomized, double-blind, placebo controlled trial to investigate the optimal dose of metoclopramide for treatment of nausea.
Detailed description
The most effective dose of metoclopramide for treatment of nausea in the emergency department setting has not been thoroughly investigated. One pilot study among emergency department patients in Australia found no statistical difference between 10 mg and 0.4 milligrams/kilogram; another investigation suggests that the anti-emetic effect of 10 milligrams of metoclopramide is no more effective than placebo. In contrast, investigations focusing on chemotherapy patients and post-operative patients suggest that higher dosage metoclopramide is more effective in treating nausea and vomiting. This emergency department study will compare the anti-emetic efficacy of 10 milligrams and 20 milligrams of metoclopramide by using the visual analog scale. In addition to evaluation of dose, we will evaluate one of the most common side affects of metoclopramide, akathisia. Akathisia is characterized by a subjective component of restlessness and an objective component in the form of the inability to remain motionless. Anti-cholinergic medications are known to reduce extrapyramidal symptoms such as akathisia when dopamine function is impaired in the basal ganglia. In fact, the use of diphenhydramine has been shown to reduce the incidence of akathisia in patients receiving a different anti-emetic, prochlorperazine. However, no research has focused on the use of anti-cholinergic medications to reduce metoclopramide induced akathisia. This investigation will assess the use of 25 mg of diphenhydramine in preventing metoclopramide induced akathisia in ED patients being treated for nausea/vomiting.
Interventions
an anti-emetic medication
used for prophylaxis against akathisia
DRUGPlacebo
placebo
DRUGMetoclopramide 20 mg
Metoclopramide 20 mg
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* primary or secondary complaints of nausea/vomiting * age 21-65
Exclusion criteria
* pregnancy * use of anti-histamine or dopamine antagonist as outpatient and/or within last 24 hours of presentation * previous adverse reaction to study medications * use of opioid medications prior to study start time within that ED visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nausea Scale | 60 minutes | Patients were asked to report their level of nausea on a scale for 0 to 10, with 0 representing no nausea and 10 the worst nausea imaginable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Akathisia | 60 minutes | The akathisia outcome was reported as follows: Either development of akathisia as measured using the Short Akathisia Instrument (Vinson DR. Journal of Emergency Medicine. 2006; 31:139-145)or use of rescue medication for treatment of akathisia.The short akathisia instrument briefly measures subjective and objective restlessness. |
Countries
United States
Participant flow
Recruitment details
Patients who presented to one ED with nausea were eligible for participation
Participants by arm
| Arm | Count |
|---|---|
| Metoclopramide 20mg+Diphenhydramine Metoclopramide 20 mg co-administered with diphenhydramine 25mg, intravenously | 72 |
| Metoclopramide 20+Placebo Metoclopramide 20 mg co-administered with placebo, intravenously | 71 |
| Metoclopramide 10 + Placebo Metoclopramide 10 mg co-administered with placebo, intravenously | 72 |
| Metoclopramide 10+Diphenhydramine Metoclopramide 10mg co-administered with diphenhydramine 25mg, intravenously | 71 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Metoclopramide 20mg+Diphenhydramine | Metoclopramide 20+Placebo | Metoclopramide 10 + Placebo | Metoclopramide 10+Diphenhydramine | Total |
|---|---|---|---|---|---|
| Age Continuous | 39 Years STANDARD_DEVIATION 12 | 42 Years STANDARD_DEVIATION 14 | 40 Years STANDARD_DEVIATION 13 | 39 Years STANDARD_DEVIATION 13 | 40 Years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 52 Participants | 52 Participants | 55 Participants | 51 Participants | 210 Participants |
| Sex: Female, Male Male | 20 Participants | 19 Participants | 17 Participants | 20 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 72 | 0 / 71 | 0 / 72 | 0 / 71 |
| serious Total, serious adverse events | 0 / 72 | 0 / 71 | 0 / 72 | 0 / 71 |
Outcome results
Primary
Nausea Scale
Patients were asked to report their level of nausea on a scale for 0 to 10, with 0 representing no nausea and 10 the worst nausea imaginable
Time frame: 60 minutes
Population: Only patients who received the investigational medication are included in this analysis. Please see the participant flow section for more details.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metoclopramide 20mg+Diphenhydramine | Nausea Scale | 0 units on a scale |
| Metoclopramide 20+Placebo | Nausea Scale | 0 units on a scale |
| Metoclopramide 10 + Placebo | Nausea Scale | 0 units on a scale |
| Metoclopramide 10+Diphenhydramine | Nausea Scale | 0 units on a scale |
Secondary
Number of Participants With Akathisia
The akathisia outcome was reported as follows: Either development of akathisia as measured using the Short Akathisia Instrument (Vinson DR. Journal of Emergency Medicine. 2006; 31:139-145)or use of rescue medication for treatment of akathisia.The short akathisia instrument briefly measures subjective and objective restlessness.
Time frame: 60 minutes
Population: Only patients who received the investigational medication are included in this analysis. Please see participant flow for details
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metoclopramide 20mg+Diphenhydramine | Number of Participants With Akathisia | 9 participants |
| Metoclopramide 20+Placebo | Number of Participants With Akathisia | 12 participants |
| Metoclopramide 10 + Placebo | Number of Participants With Akathisia | 5 participants |
| Metoclopramide 10+Diphenhydramine | Number of Participants With Akathisia | 8 participants |