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Low Dose Ketamine (LDK) Versus Morphine for Acute Pain Control in the Emergency Department

Low Dose Ketamine (LDK) Versus Morphine for Acute Pain Control in the Emergency Department

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01538745
Enrollment
45
Registered
2012-02-24
Start date
2012-02-29
Completion date
2013-06-30
Last updated
2021-02-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Abdomen, Acute, Back Pain, Flank Pain, Musculoskeletal Pain, Other Acute Pain

Keywords

Pain, Emergency Department, Morphine, Ketamine

Brief summary

The purpose of this study is to compare the safety and effectiveness of intravenous low dose ketamine (LDK) to the industry standard of morphine (MOR) in regards to controlling acute pain in the emergency department. Both LDK and morphine have side effects. The amount and character of these side effects will be compared. Additionally, the degree of sedation or agitation will be specifically measured. The aim of this current study is to make this comparison and shift the evidence for LDK use from the anecdotal to the scientific.

Detailed description

Phase 1 is a randomized, controlled, double-blinded study comparing the use of low-dose ketamine (LDK) to morphine for acute pain control in emergency department patients. A convenience sample of subjects will be enrolled from a population of patients aged 18-50 who present to the Brooke Army Medical Center Emergency Department with acute abdominal pain, flank/lumbar back pain and/or pain to the extremities. To take part in the study, a need for opioid analgesia must be indicated by the treating physician in addition to the patient meeting all other study criteria. The patient will then be randomized into one of the two treatment arms. Prior to receiving either the study medication (ketamine) or the active control (morphine) the patient will be asked to rate their pain on a numeric rating scale (NRS) with 0 being no pain and 10 being the worst pain possible. Their baseline vital signs (blood pressure, heart rate, respiratory rate and oxygen saturation) will also be documented. These vital signs and the NRS will be reassessed at 5, 10 and 20 minutes post medication dosage. At 20 minutes they will also document a Richmond Agitation Sedation Scale (RASS) score and will ask the patient if they require additional pain medication. If the patient denies the need for a second dose of medication they will continue to be re-assessed every 20 minutes (vital signs, NRS, and RASS) until either inpatient admission, discharge home, transfer to the operating room or until a total of 120 minutes after initial dosing. If at any time during the study the patient requires a second dose of pain medication, following the administration of the med, they will be assessed for vital signs at 5,10 and 20 minutes after the dose. At 20 minutes, a RASS score and NRS score will also be documented. They will then be re-assessed every 20 minutes (vital signs, NRS, and RASS) until either inpatient admission, discharge home, transfer to the operating room or until a total of 120 minutes after initial dosing. If they require a third dose of pain medication at any time during the study, this is considered a treatment failure and the treating physician will be contacted to provide any further pain control. The second phase of the study will be observational. An anonymous satisfaction survey will be provided to the treating nurse, physician or physicians assistant (PA) of the patients recruited from part one of the study. The purpose of conducting the survey is so that an observation point of view can be added to the data to provide a measure of how well the patient's pain was controlled.

Interventions

DRUGKetamine

0.3 mg/kg ketamine Intravenous push (IVP) over 5 minutes. Total of two possible doses.

DRUGMorphine

0.1 mg/kg Morphine IVP over 5 minutes. Total of two possible doses.

Sponsors

U.S. Air Force Office of the Surgeon General
CollaboratorFED
Brooke Army Medical Center
Lead SponsorFED

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
No

Inclusion criteria

* Patients age 18-59 who present to the Brooke Army Medical Center Emergency Department with acute (less than 10 days) abdominal pain, flank/lumbar back pain and or/pain to the extremities, and of sufficient severity in the judgement of the ED treating physician or PA to warrant use of intravenous opioids

Exclusion criteria

* Poor vital sign stability hypoxia: Sats\<95% hypotension: SBP\<90 hypertension: SBP\>180 heart rate: \<50 or \>120 respiratory rate: \<10 or \>30 * Altered mental status or intoxication * Patient is unwilling to participate or provide informed consent * History of chronic pain or pain syndrome with concurrent opioid medication use * fibromyalgia * Patient has received opioids and/or tramadol in the past 4 hours * Prescription pain medication use (to exclude muscle relaxants, acetaminophen or NSAIDs including toradol) in the past 4 hours * Allergy to morphine or ketamine * Sole provider status * Adverse reaction to morphine or ketamine in the past * Patients, who in the opinion of the triage nurse, require immediate analgesic relief * Patient is female of child-bearing age and unable to provide urine or serum for HCG analysis in triage * Pregnancy or breast feeding * Presence of oxygen dependent pulmonary disease, liver cirrhosis or Renal disease requiring dialysis. (as assessed by electronic chart review) * Presence of Ischemic heart disease, heart failure or unstable dysrhythmias (as assessed by electronic chart review) * Presence of intracranial mass or vascular lesion. * Presence of psychosis or hallucinations * Weight greater than 115kg or less than 45 kg * History of acute ocular/head trauma * History of increased intracranial pressure/hypertensive hydrocephalus * Non-English speaking patients

Design outcomes

Primary

MeasureTime frameDescription
Maximal Change in Numerical Rating Scale (NRS) Pain Score From Baseline NRS Pain Score5,10,20,40,60,80,100,120 minutes post doseNumerical Rating Scale (NRS) pain score is an 11-point rating scale for pain. With 0 being no pain and 10 being the worst pain imaginable.

Secondary

MeasureTime frameDescription
Time to Change in NRS Pain Score5,10, 20,40,60,80,100,120 minutesFollowing dosage with study medication, the amount of time taken to demonstrate a change in the patient's NRS pain score. Time to Change in NRS Pain Score for the Reporting Group as a whole will be made
Time to Maximal Change in NRS Pain Score5, 10, 20 minutes and then every 20 minutes to a total of 120 minutesFollowing dosage with study medication, the interval time taken to demonstrate the maximal change in the patient's NRS pain score will be reported for each group.
Incidence of Treatment Failure120 minutesRequiring more than two doses of the study medication provided for adequate pain control
Incidence of Side Effects, Including Outlying Vital Signs5,10,20,40,60,80,100,120 minutesThe patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), and all side effects at 5,10,20 minutes following medication administration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. All side effects and outlying vital signs will be documented.
Maximum Deviation From 0 on the Richmond Agitation Sedation Scale (RASS)5,10,20,40,60,80,100,120 minutesUsing 0 as the normal/baseline on the RASS, maximal deviation in either direction will be used to demonstrate the effect of the study medications on levels of sedation or agitation. Results will be reported as Richmond Agitation Sedation Scale (RASS) scores range from: * 4 Combative: Overtly combative, violent, immediate danger to staff * 3 Very agitated: Pulls or removes tube(s) or catheter(s); aggressive * 2 Agitated: Frequent non-purposeful movement * 1 Restless: Anxious but movements not aggressive. vigorous 0 Alert and calm * 1 Drowsy: Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (\>10 seconds) * 2 Light sedation: Briefly awakens with eye contact to voice (\<10 seconds) * 3 Moderate sedation: Movement or eye opening to voice (but no eye contact) * 4 Deep sedation: No response to voice, but movement or eye opening to physical stimulation * 5 Unarousable: No response to voice or physical stimulation

Countries

United States

Participant flow

Recruitment details

The study took place at a Level 1 trauma center. The patient population at SAMMC consists of active duty military personnel and their family members, retirees, as well as civilians. There are approximately 75,000 visits to the SAMMC ED annually. Enrollment occurred from February 2012 to March 2013.

Pre-assignment details

Patients were excluded if: O2 saturation \<95%, SBP \< 90mmHg or \> 180mmHg, HR\< 50 or \> 120 beats per minute, RR \< 10 or \> 30 per minute, altered mental status, intoxication, history fibromyalgia, ischemic heart disease, heart failure or unstable dysrhythmias, required pain medication immediately and cannot wait to consent

Participants by arm

ArmCount
Ketamine
0.3 MG/KG IV KETAMINE ADMINISTERED OVER 5 MINUTES. MAX DOSE OF 25MG. Ketamine : 0.3 mg/kg ketamine IVP over 5 minutes. Total of two possible doses.
24
Morphine
0.1 MG/KG IV MORPHINE ADMINSITERED OVER 5 MINUTES. MAX DOSE 8MG. Morphine : 0.1 mg/kg Morphine IVP over 5 minutes. Total of two possible doses.
21
Total45

Baseline characteristics

CharacteristicMorphineKetamineTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
21 Participants24 Participants45 Participants
Age, Continuous29.29 years
STANDARD_DEVIATION 9.78
30.75 years
STANDARD_DEVIATION 11.87
30.07 years
STANDARD_DEVIATION 10.84
Region of Enrollment
United States
21 participants24 participants45 participants
Sex: Female, Male
Female
12 Participants10 Participants22 Participants
Sex: Female, Male
Male
9 Participants14 Participants23 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 240 / 21
serious
Total, serious adverse events
0 / 240 / 21

Outcome results

Primary

Maximal Change in Numerical Rating Scale (NRS) Pain Score From Baseline NRS Pain Score

Numerical Rating Scale (NRS) pain score is an 11-point rating scale for pain. With 0 being no pain and 10 being the worst pain imaginable.

Time frame: 5,10,20,40,60,80,100,120 minutes post dose

ArmMeasureValue (MEAN)
KetamineMaximal Change in Numerical Rating Scale (NRS) Pain Score From Baseline NRS Pain Score-4.9 NRS pain scale score
MorphineMaximal Change in Numerical Rating Scale (NRS) Pain Score From Baseline NRS Pain Score-5 NRS pain scale score
Secondary

Incidence of Side Effects, Including Outlying Vital Signs

The patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), and all side effects at 5,10,20 minutes following medication administration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. All side effects and outlying vital signs will be documented.

Time frame: 5,10,20,40,60,80,100,120 minutes

ArmMeasureValue (NUMBER)
KetamineIncidence of Side Effects, Including Outlying Vital Signs58 Percentage of patients
MorphineIncidence of Side Effects, Including Outlying Vital Signs57 Percentage of patients
Secondary

Incidence of Treatment Failure

Requiring more than two doses of the study medication provided for adequate pain control

Time frame: 120 minutes

ArmMeasureValue (NUMBER)
KetamineIncidence of Treatment Failure25 Percentage of patients
MorphineIncidence of Treatment Failure14 Percentage of patients
Secondary

Maximum Deviation From 0 on the Richmond Agitation Sedation Scale (RASS)

Using 0 as the normal/baseline on the RASS, maximal deviation in either direction will be used to demonstrate the effect of the study medications on levels of sedation or agitation. Results will be reported as Richmond Agitation Sedation Scale (RASS) scores range from: * 4 Combative: Overtly combative, violent, immediate danger to staff * 3 Very agitated: Pulls or removes tube(s) or catheter(s); aggressive * 2 Agitated: Frequent non-purposeful movement * 1 Restless: Anxious but movements not aggressive. vigorous 0 Alert and calm * 1 Drowsy: Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (\>10 seconds) * 2 Light sedation: Briefly awakens with eye contact to voice (\<10 seconds) * 3 Moderate sedation: Movement or eye opening to voice (but no eye contact) * 4 Deep sedation: No response to voice, but movement or eye opening to physical stimulation * 5 Unarousable: No response to voice or physical stimulation

Time frame: 5,10,20,40,60,80,100,120 minutes

ArmMeasureValue (MEAN)
KetamineMaximum Deviation From 0 on the Richmond Agitation Sedation Scale (RASS)0 units on a scale
MorphineMaximum Deviation From 0 on the Richmond Agitation Sedation Scale (RASS)0 units on a scale
Secondary

Time to Change in NRS Pain Score

Following dosage with study medication, the amount of time taken to demonstrate a change in the patient's NRS pain score. Time to Change in NRS Pain Score for the Reporting Group as a whole will be made

Time frame: 5,10, 20,40,60,80,100,120 minutes

ArmMeasureValue (MEAN)Dispersion
KetamineTime to Change in NRS Pain Score5 minutesStandard Deviation 2.63
MorphineTime to Change in NRS Pain Score5 minutesStandard Deviation 2.48
Secondary

Time to Maximal Change in NRS Pain Score

Following dosage with study medication, the interval time taken to demonstrate the maximal change in the patient's NRS pain score will be reported for each group.

Time frame: 5, 10, 20 minutes and then every 20 minutes to a total of 120 minutes

ArmMeasureValue (MEDIAN)Dispersion
KetamineTime to Maximal Change in NRS Pain Score5 minutesStandard Deviation 1.7
MorphineTime to Maximal Change in NRS Pain Score120 minutesStandard Deviation 22.2

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026