Ketamine Sickle Cell Disease

Study Overview
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Brief Summary
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Sickle cell disease (SCD) often results in acute vaso-occlusive crisis (VOC), an obstruction of blood vessels resulting in ischemic injury and pain. The pain experienced during these episodes is due to a wide range of pathophysiological processes. Though recent studies have begun to unravel the underlying mechanisms of these processes, literature focused on pain management for sickle cell disease is scarce. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the predominate treatment for VOC. However, the efficacy of these treatments has come into question. A large sub-set of patients with SCD report continued pain despite treatment with opioids. Tolerance and opioid-induced hyperalgesia (OIH) may be responsible for unresponsiveness to opioid-centric treatment modalities. New classes of drugs are being tested to prevent and treat acute pain associated with SCD, but in the meantime physicians are looking to existing therapies to bridge the gap. The N-methyl-d-aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal models and clinical settings. Ketamine utilized as a low dose continuous infusion could benefit patients with SCD related pain that are unresponsive to opioid analgesics. Based on limited studies of adjuvant ketamine use for pain management, low-dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low-dose ketamine infusion in patients with SCD-related pain.

Official Title
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A Randomized Controlled Trial to Determine the Efficacy of Ketamine as an Adjunct for Pain Management in Patients With Sickle Cell Crisis

Conditions
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SC Disease, Pain, Chronic

Intervention / Treatment
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* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with sickle cell anemia Adults aged 18 and older Subjects who have given written consent Exclusion Criteria: Subjects who are pregnant Subjects younger than 18 years Subjects known or suspected to have an allergy to opiates/opioids, muscle relaxants or other similar medications Subjects who have a contraindication to ketamine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Prospective Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>Continuous infusion of Ketamine 0.3 to 0.5 mg/kg per hour PCA Dilaudid 2.0-2.5 mg | Drug: Ketamine<br>* Low dose continuous infusion of ketamine 0.3 to 0.5 mg/kg per hour<br>|
| No Intervention: Opioid Only<br>Patient-controlled analgesia Dilaudid 2.0-2.5 mg | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioid Use in milligrams morphine equivalents | Total opioid Use in milligrams morphine equivalents | 1-3 hours | 
| Pain scores measured on the Visual Analog Scale 0 - 10 | Pain scores measured on the Visual Analog Scale 0 - 10 | 1-3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost of pharmacotherapy | monetary cost of intervention used | 1 day | 
| Length of hospital stay | Length of stay in the hospital | 1-7 days | 
| Nausea and vomiting scores Visual Analog Scale 0 - 10 | Nausea and vomiting scores Visual Analog Scale 0 - 10 | 1-3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine