Acute Pain
Conditions
Keywords
moderate to severe pain, emergency department patient, ketamine
Brief summary
This study will prospectively compare the mean Numerical Rating Scale (NRS) pain score reduction amongst three recommended dosing strategies of intravenous ketamine (0.1 mg/kg, 0.2 mg/kg, and 0.3mg/kg) for acute pain in the emergency department (ED).This study will also examine the frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Subgroups for exploratory analysis based on the need for rescue analgesia within two hours of ketamine administration, adequate pain relief, previous opioid tolerance, and age (adults \< 65 years old and \> 65 years old).
Detailed description
A literature review was performed that searched for randomized clinical trials involving ketamine IV boluses for acute pain in the Emergency Department. Studies involving continuous infusions or intranasal routes of ketamine administration were not included. Thirteen randomized clinical trials were identified meeting this criteria. None of these trials directly compared ketamine doses within the 0.1-0.3 mg/kg range for pain score reduction and adverse events. Many of these trials concluded with the recommendation that further studies were needed to evaluate the optimal dosing of ketamine for acute pain and determine which populations are most ideal for its use. This study will be the first to evaluate ketamine for acute pain in the emergency department at standard of care doses (0.1 mg/kg, 0.2 mg/kg, and 0.3 mg/kg IV) to determine which dose correlates with the most efficacy and safety. This study will include the following procedures: * Patient consent, screening, and enrollment will be performed by the treating resident or attending who will remain blinded * Patient will be assigned a subject number * Treating resident or attending will notify the ED pharmacist that a patient has been enrolled in the trial * ED pharmacist will notify the IV room and place the study drug order * Either the ED pharmacist or a pharmacy supervisor will randomize the subject based on the predetermined randomization list * Study drug will be prepared as 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg IV dose in a 100 mL solution of dextrose 5% or sodium chloride 0.9% * ED pharmacist will promptly deliver the study drug to the ED * Baseline vital signs will be assessed prior to starting the study drug infusion * Study drug will be administered via IV infusion over 20 minutes * Treating resident or attending will reassess the patient at 15 minutes from the end of infusion, at 30 minutes from the end of infusion, and then every 30 minutes for up to 120 minutes or until discharge, whichever is sooner
Interventions
Three different doses of ketamine will be administered.
Sponsors
Hackensack Meridian Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinded study (only the pharmacist supervisor that has no other involvement with the study will know the dose)
Intervention model description
3 arms each arm getting a different dose of ketamine
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute pain (including acute on chronic pain) * Pain score of moderate to severe (\> 4/10) on the Numerical Rating Scale * Provider determines the patient requires intravenous ketamine for analgesia
Exclusion criteria
* History of hypersensitivity to ketamine * Altered mental status * Psychiatric illness * Known history of renal or hepatic insufficiency * Acute head or eye injury * Suspected intracranial hypertension or mass * Headache as the chief complaint * Alcohol or drug abuse * Received an analgesic within the last four hours * History of congestive heart failure * History of aortic or brain aneurysm * Active Chest Pain * Porphyria * Active methadone treatment * Pregnant or breastfeeding * Signs of respiratory, hemodynamic, or neurologic compromise * Systolic blood pressure \< 90 mmHg or \> 180 mmHg * Heart rate \< 50 beats per minute or \> 150 beats per minute * Respiratory rate \< 10 breaths per minute or \> 30 breaths per minute * Glasgow Coma Score \< 15 * Previously received ketamine \< 0.3 mg/kg IV for acute pain in the emergency department
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Score | Within 2 hours post infusion completion | Pain score using Numerical Rating Scale (NRS) post ketamine infusion. The Numerical Rating Scale (NRS) ranges from 0-to-10 with 0 being no pain and lower numbers representing less pain, so in this case lower numbers will represent better outcomes. Pain scores were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Within 2 hours post infusion completion | Frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Adverse events were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: 0.1 mg/kg Ketamine 0.1 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.
Ketamine Injectable Product: Three different doses of ketamine will be administered. | 5 |
| Arm 1: 0.2 mg/kg Ketamine 0.2 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.
Ketamine Injectable Product: Three different doses of ketamine will be administered. | 4 |
| Arm 1: 0.3 mg/kg Ketamine 0.3 mg/kg in a 100 mL solution of dextrose 5% or sodium chloride 0.9% will be give after patient consent and enrollment in the study, vitals are followed (heart rate, systolic blood pressure and respiratory rate) for 2 hours following completion of ketamine infusion. Evaluated for side effects for 2 hours following completion of ketamine infusion.
Ketamine Injectable Product: Three different doses of ketamine will be administered. | 2 |
| Total | 11 |
Baseline characteristics
| Characteristic | Arm 1: 0.2 mg/kg Ketamine | Arm 1: 0.3 mg/kg Ketamine | Arm 1: 0.1 mg/kg Ketamine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 1 Participants | 4 Participants | 9 Participants |
| Age, Continuous | 50.5 years | 68 years | 47.4 years | 52.3 years |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United States | 4 Participants | 2 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 2 / 5 | 3 / 4 | 2 / 2 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 0 / 2 |
Outcome results
Primary
Pain Score
Pain score using Numerical Rating Scale (NRS) post ketamine infusion. The Numerical Rating Scale (NRS) ranges from 0-to-10 with 0 being no pain and lower numbers representing less pain, so in this case lower numbers will represent better outcomes. Pain scores were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion.
Time frame: Within 2 hours post infusion completion
Population: A different number of patients was available for the pain score measurement at the different timepoints. Two patients did not complete infusion, one in the 0.1 mg/kg ketamine group and one in the 0.3 mg/kg ketamine group.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Pain score at 90 min | 4.5 score on a scale |
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Pain score at 30 min | 5.25 score on a scale |
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Pain score at 120 min | 4 score on a scale |
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Pain score at 60 min | 5.25 score on a scale |
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Pain score at 15 min | 5.25 score on a scale |
| Arm 1: 0.1 mg/kg Ketamine | Pain Score | Baseline pain score | 9.4 score on a scale |
| Arm 1: 0.2 mg/kg Ketamine | Pain Score | Pain score at 30 min | 5.75 score on a scale |
| Arm 1: 0.2 mg/kg Ketamine | Pain Score | Baseline pain score | 8.5 score on a scale |
| Arm 1: 0.2 mg/kg Ketamine | Pain Score | Pain score at 15 min | 6 score on a scale |
| Arm 1: 0.2 mg/kg Ketamine | Pain Score | Pain score at 90 min | 7 score on a scale |
| Arm 1: 0.2 mg/kg Ketamine | Pain Score | Pain score at 60 min | 7 score on a scale |
| Arm 1: 0.3 mg/kg Ketamine | Pain Score | Baseline pain score | 7.5 score on a scale |
| Arm 1: 0.3 mg/kg Ketamine | Pain Score | Pain score at 60 min | 5 score on a scale |
| Arm 1: 0.3 mg/kg Ketamine | Pain Score | Pain score at 15 min | 2 score on a scale |
| Arm 1: 0.3 mg/kg Ketamine | Pain Score | Pain score at 90 min | 2 score on a scale |
| Arm 1: 0.3 mg/kg Ketamine | Pain Score | Pain score at 30 min | 6 score on a scale |
Secondary
Adverse Events
Frequency of adverse events secondary to ketamine including fatigue, dizziness, nausea, headache, feeling of unreality, changes in hearing or vision, mood changes, generalized discomfort, and hallucinations, changes in vital signs. Adverse events were reported at baseline and then at 15 min/30 min/60 min/90 min and 120 minutes post-infusion.
Time frame: Within 2 hours post infusion completion
Population: Number of patients reporting adverse events in the two hours post infusion. Two patients did not complete infusion, one in the 0.1 mg/kg ketamine group and one in the 0.3 mg/kg ketamine group and they are not included in the AE reporting.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: 0.1 mg/kg Ketamine | Adverse Events | at 60 min post infusion | 1 participants |
| Arm 1: 0.1 mg/kg Ketamine | Adverse Events | at 15 min post infusion | 2 participants |
| Arm 1: 0.1 mg/kg Ketamine | Adverse Events | at 30 min post infusion | 1 participants |
| Arm 1: 0.1 mg/kg Ketamine | Adverse Events | at 90 min post infusion | 1 participants |
| Arm 1: 0.1 mg/kg Ketamine | Adverse Events | at 120 min post infusion | 1 participants |
| Arm 1: 0.2 mg/kg Ketamine | Adverse Events | at 120 min post infusion | 0 participants |
| Arm 1: 0.2 mg/kg Ketamine | Adverse Events | at 15 min post infusion | 3 participants |
| Arm 1: 0.2 mg/kg Ketamine | Adverse Events | at 30 min post infusion | 2 participants |
| Arm 1: 0.2 mg/kg Ketamine | Adverse Events | at 60 min post infusion | 2 participants |
| Arm 1: 0.2 mg/kg Ketamine | Adverse Events | at 90 min post infusion | 2 participants |
| Arm 1: 0.3 mg/kg Ketamine | Adverse Events | at 120 min post infusion | 0 participants |
| Arm 1: 0.3 mg/kg Ketamine | Adverse Events | at 30 min post infusion | 1 participants |
| Arm 1: 0.3 mg/kg Ketamine | Adverse Events | at 90 min post infusion | 0 participants |
| Arm 1: 0.3 mg/kg Ketamine | Adverse Events | at 15 min post infusion | 2 participants |
| Arm 1: 0.3 mg/kg Ketamine | Adverse Events | at 60 min post infusion | 0 participants |