AKTSS: Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis

• Sponsor: UCSF Benioff Children's Hospital Oakland (Other)
• Overall Status: Completed
• CT.gov ID: NCT03296345
• Collaborator: (none)
• Enrollment: 62
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

Acute vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) are primarily managed with opioids. Tolerance and hyperalgesia to opioids develops due to N-methyl-D-aspartate (NMDA)-receptor mediated activation of the nociceptive system, and as a receptor antagonist, ketamine mitigates this. Intravenous (IV) ketamine has demonstrated efficacy in reducing post-operative, chronic, and cancer-related pain in pediatrics, as well as in reducing time to pain control in the emergency department (ED) in adults. Limited studies suggest efficacy in adult opioid-refractory SCD patients. This study is investigating the safety and tolerability of adjuvant low-dose IV ketamine bolus for pediatric SCD VOE in the ED, as well as its efficacy in improving pain control and reducing hospitalization.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease; Vaso-Occlusive Crisis	Drug: Ketamine	Phase 2

Detailed Description

In this cohort study, all consenting pediatric sickle-cell patients between 10 and 25 years old who were cared for at UCSF Benioff Children's Hospital Oakland (UCSFBCHO) presenting to the emergency department for VOC were enrolled in the study. Patients were compared to themselves in a time series, pre and post exposure to the study intervention (low-dose ketamine bolus at 0.2 mg/kg x 1 prior to second dose of IV opiate). The pediatric FACES pain scale was used to measure pain scales at pre-designated time points in the ED per standard nursing protocol (FACES for younger kids, visual analog scale in adolescents/young adults). Opiate usage was summed in the ED, converted to mg/kg/hour of morphine equivalents (since different opioids agents were given to different patients based on individual historical efficacy, and since length of stay in the emergency room could affect total morphine equivalents received), and compared between the pre and post-intervention groups. In addition, length of stay, time to 50% pain control, presentation and discharge pain scores, and likelihood of discharge from the ED were compared. Data was be collected via chart review in the UCSFBCHO system by study investigators. Pre-intervention data from the past three patient encounters (e.g., the mean of the mg/kg/hour of morphine equivalents used in the last three patient encounters prior to receipt of ketamine) was compared to the post intervention data. In addition, a survey, which is attached, was given to patients/families at the time of the drug administration to attempt to discern if patients subjectively experienced improvement in their pain and if they experienced any negative side effects due to the drug administration. Monitoring for adverse events was recorded for each patient encounter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (AKTSS)
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Pain scores were collected using the FACES scale currently in place. In consenting patients, chart review was performed with the following data collected: mg/kg/hour of morphine equivalents, pain scores on admission, during the encounter, and at discharge, the time to 50% pain reduction, and whether or not the patient was discharged. In addition, a survey, which is attached, was given to patients/families at the time of drug administration to determine if they experienced a subjective improvement in their pain and if they suffered any undue side effects due to drug administration.	Drug: Ketamine; The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).; Other Names: Ketalar
No Intervention: Historical Control Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] [18 months]

   The number of serious and minor adverse events was measured via patient-completed survey as well as by nurse and medical providers on presentation to the emergency department (ED). Serious adverse events are defined as cardiorespiratory events requiring intervention. Minor adverse events are defined as nausea/vomiting, emergence reaction (dysphoria; hallucinations; frightening dreams), and a sense of de-realization or "dreamy" sensation. Both study providers and patients themselves, via a survey that the parent and/or patient (based on age) fills out post receipt of ketamine, reported serious and minor adverse events.

Secondary Outcome Measures

1. Effect of Low-dose Ketamine (LDK) on Opioid Usage in the ED [Up to one year prior and after LDK administration on day 1 of the study in the ED]

   Opioid usage for at least one but up to three prior patient visits in the last one year for each patient enrolled in the study was summarized, expressed as morphine equivalents in mg/kg/h, to account for different types of opioids used per patient preference, and then this was compared to the intervention group that received LDK. Percent change in opioid usage (expressed as morphine equivalents in mg/kg/h) is reported).

2. Effect of Low-dose Ketamine on Pain Scores on Presentation to the ED [Up to one year prior and on presentation to the ED after LDK administration]

   Patient pain scores at presentation for the enrolled encounters and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

3. Effect of Low-dose Ketamine on Discharge Rates From the ED [Up to one year prior to receipt of ketamine for the historical control arm/group and up to 18 months for the intervention arm/group]

   Percent discharge from the ED for intervention group and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. Participants were assigned a "0" if discharged or "1" if not discharged.

4. Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey [after LDK administration on day 1 of the study in the ED]

   After receipt of LDK, patients and/or their parents, based on age, filled out a survey based on a Likert scale regarding their agreement (Strongly Disagree to Strongly Agree) with the following statements: Achieved faster pain relief with LDK, Achieved more complete pain relief with LDK, and Desire to receive LDK in a future vaso-occlusive crisis. There is also an area where patients could provide general comments regarding their experience in receiving LDK. Count of Participants who agree or strongly agree for each question are reported.

5. Effect of Low-dose Ketamine on Patient Pain Scores on Discharge From the ED/Admission to the Hospital [At time of discharge from the ED/admission to the hospital (up to one year prior and after LDK administration)]

   Patient pain scores at time of discharge from the ED/admission to the hospital for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain scores post receipt of ketamine are presented for the intervention group. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

6. Effect of Low-dose Ketamine on Percent Difference of Length of Stay (LOS) in the ED [Up to one year prior to and after LDK administration on day 1 of the study in the ED]

   Length of stay (LOS) in minutes in the ED for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed.

7. Effect of Low-dose Ketamine on Time to 50% Pain Reduction [Up to one year prior to and after LDK administration on day 1 of the study in the ED]

   Time to 50% pain reduction (pain reported 50% less than baseline) in minutes for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed as historical controls. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 25 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• All English-speaking, sickle cell patients who receive their care at UCSFBCHO in the Department of Hematology who are 8-to-25-years-old presenting to the emergency department for VOC were asked to enroll.

Exclusion Criteria:

• Prior adverse reaction to ketamine

• Patients were asked during the consent process if they have ever received ketamine, and if so, if they had any serious adverse reaction, such as difficulty breathing, dysphoria, hallucinations, or allergic reaction. If they have, ketamine was not given to these patients.

• Patients who have received ketamine and experienced nausea or vomiting will be asked if they wish to receive the medication. If they do not, they did not receive ketamine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Benioff Children's Hospital and Research Center Oakland	Oakland	California	United States	94609

Sponsors and Collaborators

• UCSF Benioff Children's Hospital Oakland

Investigators

• Principal Investigator: Jonathan B Cooper-Sood, MD, Children's Hospital and Research Center of Oakland

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 28, 2017

More Information

Publications

• Ahern TL, Herring AA, Anderson ES, Madia VA, Fahimi J, Frazee BW. The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED. Am J Emerg Med. 2015 Feb;33(2):197-201. doi: 10.1016/j.ajem.2014.11.010. Epub 2014 Nov 15.
• Beaudoin FL, Lin C, Guan W, Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial. Acad Emerg Med. 2014 Nov;21(11):1193-202. doi: 10.1111/acem.12510.
• Drake AB, Milne WK, Carpenter CR. Hot Off the Press: Subdissociative-dose Ketamine for Acute Pain in the Emergency Department. Acad Emerg Med. 2015 Jul;22(7):887-9. doi: 10.1111/acem.12705. Epub 2015 Jun 30.
• Jennings CA, Bobb BT, Noreika DM, Coyne PJ. Oral ketamine for sickle cell crisis pain refractory to opioids. J Pain Palliat Care Pharmacother. 2013 Jun;27(2):150-4. doi: 10.3109/15360288.2013.788599. Epub 2013 May 21.
• Miller JP, Schauer SG, Ganem VJ, Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015 Mar;33(3):402-8. doi: 10.1016/j.ajem.2014.12.058. Epub 2015 Jan 7.
• Neri CM, Pestieau SR, Darbari DS. Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth. 2013 Aug;23(8):684-9. doi: 10.1111/pan.12172. Epub 2013 Apr 9. Review.
• Riha H, Aaronson P, Schmidt A. Evaluation of analgesic effects of ketamine through sub-dissociative dosing in the ED. Am J Emerg Med. 2015 Jun;33(6):847-9. doi: 10.1016/j.ajem.2015.03.045. Epub 2015 Mar 25. Review.
• Tawfic QA, Faris AS, Eipe N. Sickle cell pain management: are we missing the role of pronociception and neuropathic pain? Paediatr Anaesth. 2013 Nov;23(11):1104-5. doi: 10.1111/pan.12269.
• Tawfic QA, Faris AS, Kausalya R. The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease. J Pain Symptom Manage. 2014 Feb;47(2):334-40. doi: 10.1016/j.jpainsymman.2013.03.012. Epub 2013 Jul 12.
• Uprety D, Baber A, Foy M. Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature. Ann Hematol. 2014 May;93(5):769-71. doi: 10.1007/s00277-013-1954-3. Epub 2013 Nov 15. Review.
• Zempsky WT, Loiselle KA, Corsi JM, Hagstrom JN. Use of low-dose ketamine infusion for pediatric patients with sickle cell disease-related pain: a case series. Clin J Pain. 2010 Feb;26(2):163-7. doi: 10.1097/AJP.0b013e3181b511ab.

• Responsible Party: UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT03296345
• Other Study ID Numbers: 2010-010
• First Posted: Sep 28, 2017
• Last Update Posted: Apr 20, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by UCSF Benioff Children's Hospital Oakland: Ketamine; Sickle Cell Disease; Vaso-Occlusive Episode
• Additional relevant MeSH terms: Anemia, Sickle Cell; Ketamine

Study Results

Participant Flow

Arm/Group Title	Study Participants
Arm/Group Description	Intervention: Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study. Historical Control: Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Period Title: Overall Study
STARTED	62
COMPLETED	62
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Study Participants
Arm/Group Description	Intervention: Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).
Overall Participants	62
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	18.1
Sex: Female, Male (Count of Participants)
Female	45 72.6%
Male	17 27.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	61 98.4%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	1 1.6%
Site of pain on presentation (participants) [Number]
Back	22 35.5%
Extremity	16 25.8%
Chest	12 19.4%
Whole body	5 8.1%
Abdomen	4 6.5%
Other	3 4.8%
Unknown	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Description	The number of serious and minor adverse events was measured via patient-completed survey as well as by nurse and medical providers on presentation to the emergency department (ED). Serious adverse events are defined as cardiorespiratory events requiring intervention. Minor adverse events are defined as nausea/vomiting, emergence reaction (dysphoria; hallucinations; frightening dreams), and a sense of de-realization or "dreamy" sensation. Both study providers and patients themselves, via a survey that the parent and/or patient (based on age) fills out post receipt of ketamine, reported serious and minor adverse events.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.
Measure Participants	62
Serious adverse events	0 0%
Nausea/vomiting	4 6.5%
Emergence of emergence-like symptoms	4 6.5%
Dream-like/de-realized sensation	26 41.9%
Blurry vision	3 4.8%
Dizziness	2 3.2%
Floating sensation	1 1.6%
Heavy sensation	1 1.6%
Dry mouth	1 1.6%
No adverse event	20 32.3%

2. Secondary Outcome

Title	Effect of Low-dose Ketamine (LDK) on Opioid Usage in the ED
Description	Opioid usage for at least one but up to three prior patient visits in the last one year for each patient enrolled in the study was summarized, expressed as morphine equivalents in mg/kg/h, to account for different types of opioids used per patient preference, and then this was compared to the intervention group that received LDK. Percent change in opioid usage (expressed as morphine equivalents in mg/kg/h) is reported).
Time Frame	Up to one year prior and after LDK administration on day 1 of the study in the ED

Outcome Measure Data

Analysis Population Description

62 enrolled patient-encounters were compared to their prior visits individually. At least one but up to three prior visits were averaged and compared to the intervention visit.

Arm/Group Title	Intervention
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.
Measure Participants	62
Mean (95% Confidence Interval) [percent change]	-15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intervention
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15
	Confidence Interval	(2-Sided) 95%; -28 to -2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Effect of Low-dose Ketamine on Pain Scores on Presentation to the ED
Description	Patient pain scores at presentation for the enrolled encounters and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
Time Frame	Up to one year prior and on presentation to the ED after LDK administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Historical Control
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Measure Participants	62	62
Mean (95% Confidence Interval) [Score on a scale]	9.23	9.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intervention, Historical Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Effect of Low-dose Ketamine on Discharge Rates From the ED
Description	Percent discharge from the ED for intervention group and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. Participants were assigned a "0" if discharged or "1" if not discharged.
Time Frame	Up to one year prior to receipt of ketamine for the historical control arm/group and up to 18 months for the intervention arm/group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Historical Control
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Measure Participants	62	62
Number [percentage of participants]	33 53.2%	17 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intervention, Historical Control
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey
Description	After receipt of LDK, patients and/or their parents, based on age, filled out a survey based on a Likert scale regarding their agreement (Strongly Disagree to Strongly Agree) with the following statements: Achieved faster pain relief with LDK, Achieved more complete pain relief with LDK, and Desire to receive LDK in a future vaso-occlusive crisis. There is also an area where patients could provide general comments regarding their experience in receiving LDK. Count of Participants who agree or strongly agree for each question are reported.
Time Frame	after LDK administration on day 1 of the study in the ED

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.
Measure Participants	62
Achieved faster pain relief?	43 69.4%
Achieved more complete pain relief?	30 48.4%
Desire to receive LDK in the future?	49 79%

6. Secondary Outcome

Title	Effect of Low-dose Ketamine on Patient Pain Scores on Discharge From the ED/Admission to the Hospital
Description	Patient pain scores at time of discharge from the ED/admission to the hospital for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain scores post receipt of ketamine are presented for the intervention group. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
Time Frame	At time of discharge from the ED/admission to the hospital (up to one year prior and after LDK administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Historical Control
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Measure Participants	62	62
Mean (95% Confidence Interval) [Score on a scale]	7.15	7.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intervention, Historical Control
	Comments
	Type of Statistical Test	Other
	Comments	A Wilcoxon sign-rank, given non parametric data, was used to compare the intervention and historical control groups for statistical significance, while a student's t-test was used to estimate effect size
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Effect of Low-dose Ketamine on Percent Difference of Length of Stay (LOS) in the ED
Description	Length of stay (LOS) in minutes in the ED for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed.
Time Frame	Up to one year prior to and after LDK administration on day 1 of the study in the ED

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Historical Control
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Measure Participants	62	62
Mean (95% Confidence Interval) [LOS in minutes]	273.5	217.3

8. Secondary Outcome

Title	Effect of Low-dose Ketamine on Time to 50% Pain Reduction
Description	Time to 50% pain reduction (pain reported 50% less than baseline) in minutes for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed as historical controls. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).
Time Frame	Up to one year prior to and after LDK administration on day 1 of the study in the ED

Outcome Measure Data

Analysis Population Description

16 participants reported a 50% pain reduction, and those 16 participants were included in the analysis of time to 50% pain reduction.

Arm/Group Title	Intervention	Historical Control
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner.
Measure Participants	16	16
Mean (95% Confidence Interval) [time to 50% pain reduction in minutes]	116.1	167.3

Adverse Events

Time Frame	18 months
Adverse Event Reporting Description	Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
Arm/Group Title	Intervention
Arm/Group Description	Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.
All Cause Mortality
	Intervention
	Affected / at Risk (%)	# Events
Total	0/62 (0%)
Serious Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	0/62 (0%)
Other (Not Including Serious) Adverse Events
	Intervention
	Affected / at Risk (%)	# Events
Total	42/62 (67.7%)
Eye disorders
Blurry vision	3/62 (4.8%)
Gastrointestinal disorders
Nausea/vomiting	4/62 (6.5%)
General disorders
Emergence of emergence-like symptoms	4/62 (6.5%)
Dream-like/de-realized sensation	26/62 (41.9%)
Floating sensation	1/62 (1.6%)
Heavy sensation	1/62 (1.6%)
Dry mouth	1/62 (1.6%)
Vascular disorders
Dizziness	2/62 (3.2%)

Limitations/Caveats

Given the study design (non-blinded, non-randomized), the effect of LDK on opioid usage and other secondary outcomes cannot be definitively associated with LDK itself given the possibility of a placebo effect.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.