Low-Dose Ketamine Infusion for Children With Sickle Cell Disease-Related Pain
| Status: | Terminated |
|---|---|
| Conditions: | Anemia |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 7 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2008 |
| End Date: | June 2011 |
Use of Low-Dose Ketamine Infusion in Acute Painful Episodes of Sickle Cell Disease: A Pilot Study
Acute pain episodes associated with sickle cell disease (SCD) are very difficult to manage
effectively. Opioid tolerance and side effects have been major roadblocks in our ability to
provide these patients with adequate pain relief. This pilot study is designed to examine
the safety and feasibility of using ketamine, an N-methyl-D-aspartate (NMDA) receptor
antagonist, in the inpatient seeing with children and adolescents who have sickle cell
vasoocclusive pain. Previous research suggests that in subanesthetic doses, ketamine may be
able to prevent the development of opiate tolerance and facilitate better pain relief with
lower opiate doses, allowing for less respiratory depression, less sedation, easier
ambulation, less deconditioning, shorter hospital stays, and better quality of life. The
goal of this pilot study is to evaluate the safety and feasibility of using a continuous
infusion of ketamine, in conjunction with opiates, in the inpatient setting for sickle cell
vasoocclusive pain. It is hypothesized that using a low dose ketamine infusion in
conjunction with opiates will be a safe and feasible practice for the treatment of sickle
cell pain.
effectively. Opioid tolerance and side effects have been major roadblocks in our ability to
provide these patients with adequate pain relief. This pilot study is designed to examine
the safety and feasibility of using ketamine, an N-methyl-D-aspartate (NMDA) receptor
antagonist, in the inpatient seeing with children and adolescents who have sickle cell
vasoocclusive pain. Previous research suggests that in subanesthetic doses, ketamine may be
able to prevent the development of opiate tolerance and facilitate better pain relief with
lower opiate doses, allowing for less respiratory depression, less sedation, easier
ambulation, less deconditioning, shorter hospital stays, and better quality of life. The
goal of this pilot study is to evaluate the safety and feasibility of using a continuous
infusion of ketamine, in conjunction with opiates, in the inpatient setting for sickle cell
vasoocclusive pain. It is hypothesized that using a low dose ketamine infusion in
conjunction with opiates will be a safe and feasible practice for the treatment of sickle
cell pain.
3.2 Study Design/Type
1. Patient meeting inclusion/exclusion criteria is enrolled up to 24 hours after admission
for a vasoocclusive episode.
2. Prior to onset of ketamine infusion, the following information is collected:
1. Demographic information (age, gender, SCD genotype, past history of SCD-related
complications) [Obtained from the patient's medical chart]
2. Opiate utilization/hour since admission [Obtained from the patient's medical
chart]
3. Numerical Rating Scale (NRS) scores since admission [Obtained from the patient's
medical chart]
4. Sedation score (University of Michigan Sedation Scale) is obtained [By the nursing
staff]
5. Body outline figure of the Adolescent Pediatric Pain Tool (validated down to age
7) is administered [By the research staff]
6. Ketamine Effects Scale (KES) is administered to the patient [By the research
staff]
3. Ketamine infusion is begun at 0.05 mg/kg/hour.
4. After infusion is initiated:
1. Vital signs are taken every hour for two hours after infusion begins, then after
two hours, then every four hours for the remainder of the hospitalization
[Completed by the nursing staff]
2. Pain scores are recorded with vital signs if the patient is awake [Completed by
nursing staff]
3. Patient is also asked if pain is a lot better, a little better, no change, a
little worse, or a lot worse than previous assessment [Completed by nursing staff]
4. Sedation score (University of Michigan Sedation Scale) assessed with pain score
[Completed by the nursing staff]
5. Adolescent Pediatric Pain Tool (APPT) body outline figure is completed by the
patient once per day between 3 pm and 5 pm. [Administered by the research staff]
6. Ketamine Effects Scale (KES) is administered to the patient once per day between
3pm and 5pm [By the research staff]
7. Patient is monitored for side effects including dreams, disorientation, dysphoria,
agitation, CNS depression, respiratory depression, increasing hypoxia, nausea, or
vomiting [Completed by the nursing or research staff]
8. Need for supplemental oxygen is recorded (oxygen saturation <95%) [Completed by
nursing staff]
9. Opiate use and NSAID use/6 hours is recorded [Completed by the nursing or research
staff]
5. The infusion may be discontinued or decreased at any time due to unacceptable side
effects as determined by the clinician, patient, parent, or principal investigator.
6. Agents designed to reduce ketamine side effects [midazolam (Versed), clonidine,
lorazepam (Ativan), or diazepam (Valium)] may be administered at the discretion of the
attending physician or the principal investigator.
7. 4 hours or more after infusion begins, the infusion rate may be increased to 0.1
mg/kg/hour if the following parameters are met:
1. patient's pain has not improved to an acceptable range (pain score is still ≥5)
2. side effects remain acceptable
8. 4 hours or more after the previous increase the ketamine infusion may be increased to
0.15 mg/kg/hour per parameters.
9. 4 hours of more after the previous increase the ketamine infusion may be increased to
0.2 mg/kg/hour per parameters.
10. The ketamine infusion will be discontinued at the time of transition to oral pain
medication, or no more than 72 hours after initiation, or at the request of the
clinician, patient, parent, or principal investigator.
11. Pain scores, vital signs, sedation score, opiate use, APPT body outline figure, and KES
score will be recorded as above for the remainder of the hospitalization.
12. Total length of hospitalization will be recorded.
13. Patient will be contacted on a weekly basis for 4 weeks following hospitalization for
review of potential side effects, pain episodes, or events leading to re-admission.
14. The patient's medical record will be reviewed to determine duration of previous
hospitalizations for SCD pain in the previous 24 months and opiate utilization, pain
scores, and transition to oral opiates during those hospitalizations.
3.3 Randomization
This will be conducted as a pilot study; patients will not be randomized.
3.4 Duration
The length of the patient's participation in this study is the duration of their
hospitalization, as well as 4 weeks worth of follow-up phone calls.
3.5 Discontinuation
Individual patients will stop receiving ketamine if they develop acute chest syndrome (ACS),
have a stroke, are transferred to the Intensive Care Unit (ICU), if their hemoglobin falls
below 5 mg/dl, if they experience unacceptable side effects, or at the request of the PI,
attending, patient, or parent. However, they will continue to be in the study and all data
will be collected throughout the duration of their hospitalization.
The entire trial will be terminated when 20 patients have completed the protocol, or if
there is an unexpected rate of acute chest syndrome or admissions to the pediatric intensive
care unit (PICU).
1. Patient meeting inclusion/exclusion criteria is enrolled up to 24 hours after admission
for a vasoocclusive episode.
2. Prior to onset of ketamine infusion, the following information is collected:
1. Demographic information (age, gender, SCD genotype, past history of SCD-related
complications) [Obtained from the patient's medical chart]
2. Opiate utilization/hour since admission [Obtained from the patient's medical
chart]
3. Numerical Rating Scale (NRS) scores since admission [Obtained from the patient's
medical chart]
4. Sedation score (University of Michigan Sedation Scale) is obtained [By the nursing
staff]
5. Body outline figure of the Adolescent Pediatric Pain Tool (validated down to age
7) is administered [By the research staff]
6. Ketamine Effects Scale (KES) is administered to the patient [By the research
staff]
3. Ketamine infusion is begun at 0.05 mg/kg/hour.
4. After infusion is initiated:
1. Vital signs are taken every hour for two hours after infusion begins, then after
two hours, then every four hours for the remainder of the hospitalization
[Completed by the nursing staff]
2. Pain scores are recorded with vital signs if the patient is awake [Completed by
nursing staff]
3. Patient is also asked if pain is a lot better, a little better, no change, a
little worse, or a lot worse than previous assessment [Completed by nursing staff]
4. Sedation score (University of Michigan Sedation Scale) assessed with pain score
[Completed by the nursing staff]
5. Adolescent Pediatric Pain Tool (APPT) body outline figure is completed by the
patient once per day between 3 pm and 5 pm. [Administered by the research staff]
6. Ketamine Effects Scale (KES) is administered to the patient once per day between
3pm and 5pm [By the research staff]
7. Patient is monitored for side effects including dreams, disorientation, dysphoria,
agitation, CNS depression, respiratory depression, increasing hypoxia, nausea, or
vomiting [Completed by the nursing or research staff]
8. Need for supplemental oxygen is recorded (oxygen saturation <95%) [Completed by
nursing staff]
9. Opiate use and NSAID use/6 hours is recorded [Completed by the nursing or research
staff]
5. The infusion may be discontinued or decreased at any time due to unacceptable side
effects as determined by the clinician, patient, parent, or principal investigator.
6. Agents designed to reduce ketamine side effects [midazolam (Versed), clonidine,
lorazepam (Ativan), or diazepam (Valium)] may be administered at the discretion of the
attending physician or the principal investigator.
7. 4 hours or more after infusion begins, the infusion rate may be increased to 0.1
mg/kg/hour if the following parameters are met:
1. patient's pain has not improved to an acceptable range (pain score is still ≥5)
2. side effects remain acceptable
8. 4 hours or more after the previous increase the ketamine infusion may be increased to
0.15 mg/kg/hour per parameters.
9. 4 hours of more after the previous increase the ketamine infusion may be increased to
0.2 mg/kg/hour per parameters.
10. The ketamine infusion will be discontinued at the time of transition to oral pain
medication, or no more than 72 hours after initiation, or at the request of the
clinician, patient, parent, or principal investigator.
11. Pain scores, vital signs, sedation score, opiate use, APPT body outline figure, and KES
score will be recorded as above for the remainder of the hospitalization.
12. Total length of hospitalization will be recorded.
13. Patient will be contacted on a weekly basis for 4 weeks following hospitalization for
review of potential side effects, pain episodes, or events leading to re-admission.
14. The patient's medical record will be reviewed to determine duration of previous
hospitalizations for SCD pain in the previous 24 months and opiate utilization, pain
scores, and transition to oral opiates during those hospitalizations.
3.3 Randomization
This will be conducted as a pilot study; patients will not be randomized.
3.4 Duration
The length of the patient's participation in this study is the duration of their
hospitalization, as well as 4 weeks worth of follow-up phone calls.
3.5 Discontinuation
Individual patients will stop receiving ketamine if they develop acute chest syndrome (ACS),
have a stroke, are transferred to the Intensive Care Unit (ICU), if their hemoglobin falls
below 5 mg/dl, if they experience unacceptable side effects, or at the request of the PI,
attending, patient, or parent. However, they will continue to be in the study and all data
will be collected throughout the duration of their hospitalization.
The entire trial will be terminated when 20 patients have completed the protocol, or if
there is an unexpected rate of acute chest syndrome or admissions to the pediatric intensive
care unit (PICU).
Inclusion Criteria:
- CCMC: Children ages 7-22 years (inclusive) with documented sickle cell disease
- UCHC: Adults 18 years (inclusive) and above with documented sickle cell disease
- Sudden onset of acute pain consistent with a vasoocclusive episode -Pain requiring
hospitalization, placement on pain protocol, and patient- controlled opiates
- Pain score of greater than or equal to 5 out of 10 when ketamine infusion is started
- Cognitive ability to report pain on a 0 to 10 Numerical Rating Scale (NRS)
- At least one prior hospitalization for vasoocclusive pain at CCMC in the previous 24
months
- Parental consent and child assent
Exclusion Criteria:
- Children hospitalized for a primary diagnosis other than vasoocclusive episode
- Concurrent Acute Chest Syndrome (ACS)
- Hemoglobin < 5 mg/dL
- Concurrent history of glaucoma or raised intracranial pressure
- Signs or symptoms consistent with stroke
- History of liver or renal dysfunction
- Pregnancy (females age 12 and above must have pregnancy test)
- Simultaneous participation in investigational drug study
- Primary language spoken other than English
- No hospitalizations to CCMC for vasoocclusive pain in the previous 24 months
We found this trial at
2
sites
263 Farmington Ave
Farmington, Connecticut 06030
Farmington, Connecticut 06030
(860) 679-2000
University of Connecticut Health Center UConn Health is a vibrant, integrated academic medical center that...
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Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
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