Acute Pain, Pain
Conditions
Brief summary
This study investigates the use of low doses of ketamine, along with opiate pain medication, is more effective at controlling the acute pain of patients in the emergency department than opiate pain medication alone. In addition, this study examines whether patients treated with low doses of ketamine, along with opiate pain medication, will require less opiate pain medication to control their pain, and whether these patients are equally happy with their pain control as patients who receive only opiate pain medication.
Detailed description
This randomized, double blinded, placebo controlled study investigates the use of low-dose ketamine, in conjunction to standard opiate treatment, as compared to placebo plus standard opiate treatment, for acute painful conditions in the ED setting. The investigators hypothesize that patients treated with ketamine will require less opiate for similar levels of pain relief up to 2 hours from initiation of treatment, with similar levels of patient satisfaction and an acceptable side effect profile. Once seen by a physician, potential patients will receive provider-determined opiate treatment for their painful condition, prior to the informed consent process to ensure that treatment is not delayed. Once identified for inclusion, patients will receive informed consent and, upon consent, will subsequently be randomized through block randomization into one of two study groups. Each study group will contain at least 50 subjects. Randomization will be determined using a table of random numbers, using a restricted randomization scheme to ensure roughly equal numbers in each group. Group assignments will be sealed in opaque envelopes to be opened sequentially by the investigators. Group assignments will not indicate whether it is the treatment or the control group. At this time (T0), an initial NRS-11 score will be obtained. The NRS-11 is an 11-point scale on which patients rate their level of pain from 0 (no pain) to 10 (worst pain imaginable). If, after initial analgesic, pain level is \<6, patients will be asked again in 15 min. If at this time it is still \<6, they will not proceed in the study. The intervention group will receive 0.1 mg/kg of ketamine given over 1 minute, and the control group will receive an equivalent volume of normal saline; both groups will have received a provider-determined dose of opiate analgesia prior to enrollment. At thirty-minute intervals, subjects will be asked their level of pain, if they need more pain control and will be evaluated for the presence of side effects (hallucinations, dysphoria, weakness, diplopia, nausea, vomiting, dizziness, itching and bradypnea) as well as sedation as defined by Ramsay score of greater than 2. Repeat doses of pain medication will be given as 0.05 mg/kg morphine or equivalent dose of opioid analgesic. Total opiate dosage and number of repeat doses given at the end of 120 minutes will be recorded. At each time interval, as well as at the end of 120 minutes (T120), patient satisfaction with pain control will be recoded on the 4-point Likert scale, with 0 being completely unsatisfied and 3 being very satisfied.
Interventions
DRUGKetamine
0.1mg/kg ketamine IV
DRUGNormal Saline
1ml/kg normal saline placebo
DRUGopiate analgesic
0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request
Sponsors
Virginia Polytechnic Institute and State University
University of Memphis
Carilion Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Greater than 18 years but less than 70 years old. * Exhibiting pain defined on a numerical rating scale (NRS-11 \[Farrar et al. 2001\]) score of equal to or greater than 6 out of 10 * Deemed by the treating EM physician to require opioid analgesia.
Exclusion criteria
* Respiratory, hemodynamic or neurologic compromise, as determined by observation of signs of respiratory distress, systolic blood pressure less than 90 mmHg or systolic/diastolic blood pressure greater than 160/90, or a Glasgow -Coma Score less than 15. * A history of chronic ventilation, dialysis or with previously diagnosed cirrhosis or hepatitis by istory. * Active psychosis. * Clinical intoxication. * Known sensitivity to any study drug. * An inability to understand the NRS-11 pain measurement scale. * Presentation with headache or chest pain. * Pregnancy. * A lack of decision-making capacity. * A pain score less than 6 on the NRS-11 scale. * A concern by the treating physician or study personnel of current or prior history of narcotic abuse, or other secondary gain. * Previously participated in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Level of Pain Control as Reported on the NRS-11 | 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration | Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). Initial group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration). |
| Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | 0 min, 30 min, 60 min, 90 min, 120 min post medication administration | Patient-reported score regarding satisfaction with pain control, reported on a 4-point Likert scale (1-4, where 1 is the lowest satisfaction score possible and 4 is the highest satisfaction score possible). No data is reported for T = 0 min, as that assessment was conducted concurrently with initial medication dosing (since patients were at that point receiving their first pain control efforts, they could not yet assess their satisfaction with those efforts). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Opiate Dosage Between Study Arms in Morphine Equivalents | 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration | Average difference in opiate dosage between study arms, calculated in morphine equivalents. Initial indicates at first dose of opioid administration, up to 20 mins prior to study drug administration, and from 0 min to 120 min after study drug administration. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine 0.1 mg/kg ketamine + opiate analgesic
Ketamine: 0.1mg/kg ketamine IV
opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request | 53 |
| Placebo 0.1 mL/kg normal saline + opiate analgesic
Normal Saline: 1ml/kg normal saline placebo
opiate analgesic: 0.1mg/kg dose of morphine (or morphine equivalent) at 30 min time intervals based on patient pain score or more frequently upon request | 63 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Oversedation | 1 | 1 |
| Overall Study | Time to med. admin. > protocol limit | 1 | 1 |
Baseline characteristics
| Characteristic | Ketamine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.77 years | 41.43 years | 42.46 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 63 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 53 participants | 63 participants | 116 participants |
| Sex: Female, Male Female | 22 Participants | 29 Participants | 51 Participants |
| Sex: Female, Male Male | 31 Participants | 34 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 53 | 0 / 63 |
| serious Total, serious adverse events | 0 / 53 | 0 / 63 |
Outcome results
Primary
Change in Level of Pain Control as Reported on the NRS-11
Patient-reported pain scores on numerical rating scale (NRS) -11 pain scale (where 0 indicates no pain at all, 10 indicates the most severe pain). Initial group were patients enrolled and randomized in to the study, assessments were taken at the time of enrollment/randomization in to the study (up to 20 min prior to T=0). T = 0 min assessments were conducted at the time of medication administration (study allowed for an up to 20-minute delay in receiving study drug in order to retrieve study drug from secure storage, nursing documentation and patient verification prior to administration).
Time frame: 20 min pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Population: Total number of study subjects; received intervention or placebo.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | Initial | 9.38 Units on a scale (1-10) | Standard Deviation 0.97 |
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | T = 0 min | 7.51 Units on a scale (1-10) | Standard Deviation 1.53 |
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | T = 30 min | 5.25 Units on a scale (1-10) | Standard Deviation 2.58 |
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | T = 60 min | 5.31 Units on a scale (1-10) | Standard Deviation 2.79 |
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | T = 90 min | 4.51 Units on a scale (1-10) | Standard Deviation 2.63 |
| Ketamine | Change in Level of Pain Control as Reported on the NRS-11 | T = 120 min | 4.24 Units on a scale (1-10) | Standard Deviation 2.95 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | T = 90 min | 6.21 Units on a scale (1-10) | Standard Deviation 2.63 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | Initial | 9.44 Units on a scale (1-10) | Standard Deviation 1.43 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | T = 60 min | 6.18 Units on a scale (1-10) | Standard Deviation 2.68 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | T = 0 min | 8.10 Units on a scale (1-10) | Standard Deviation 1.3 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | T = 120 min | 5.68 Units on a scale (1-10) | Standard Deviation 2.3 |
| Placebo | Change in Level of Pain Control as Reported on the NRS-11 | T = 30 min | 2.27 Units on a scale (1-10) | Standard Deviation 0.84 |
Primary
Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale
Patient-reported score regarding satisfaction with pain control, reported on a 4-point Likert scale (1-4, where 1 is the lowest satisfaction score possible and 4 is the highest satisfaction score possible). No data is reported for T = 0 min, as that assessment was conducted concurrently with initial medication dosing (since patients were at that point receiving their first pain control efforts, they could not yet assess their satisfaction with those efforts).
Time frame: 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Population: Study subject-reported satisfaction with their pain control beginning at T = 30 minutes post-medication administration. Some study subjects were discharged, admitted or went to the operating room prior to this time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 30 min | 2.09 Units on a scale (1-4) | Standard Deviation 0.88 |
| Ketamine | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 90 min | 2.54 Units on a scale (1-4) | Standard Deviation 0.65 |
| Ketamine | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 60 min | 2.38 Units on a scale (1-4) | Standard Deviation 0.76 |
| Ketamine | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 120 min | 2.66 Units on a scale (1-4) | Standard Deviation 0.67 |
| Placebo | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 120 min | 2.52 Units on a scale (1-4) | Standard Deviation 0.5 |
| Placebo | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 30 min | 2.27 Units on a scale (1-4) | Standard Deviation 1.43 |
| Placebo | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 60 min | 2.33 Units on a scale (1-4) | Standard Deviation 0.88 |
| Placebo | Change in Patient Satisfaction With Pain Control on a 1-4 Likert Scale | T = 90 min | 2.38 Units on a scale (1-4) | Standard Deviation 0.64 |
Secondary
Difference in Opiate Dosage Between Study Arms in Morphine Equivalents
Average difference in opiate dosage between study arms, calculated in morphine equivalents. Initial indicates at first dose of opioid administration, up to 20 mins prior to study drug administration, and from 0 min to 120 min after study drug administration.
Time frame: 20 mins pre-medication administration, 0 min, 30 min, 60 min, 90 min, 120 min post medication administration
Population: Total number of patients receiving study intervention or placebo (less the two patients who were enrolled but did not receive medication within the protocol-defined time limit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine | Difference in Opiate Dosage Between Study Arms in Morphine Equivalents | Initial Narcotic Dosage | 5.41 Milligrams of Morphine Equivalent | Standard Deviation 2.77 |
| Ketamine | Difference in Opiate Dosage Between Study Arms in Morphine Equivalents | Total Narcotic Dosage | 9.95 Milligrams of Morphine Equivalent | Standard Deviation 5.83 |
| Placebo | Difference in Opiate Dosage Between Study Arms in Morphine Equivalents | Initial Narcotic Dosage | 5.83 Milligrams of Morphine Equivalent | Standard Deviation 2.27 |
| Placebo | Difference in Opiate Dosage Between Study Arms in Morphine Equivalents | Total Narcotic Dosage | 12.81 Milligrams of Morphine Equivalent | Standard Deviation 6.81 |