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Never IRB approved, no intention to proceed with the study
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine | Experimental | Continuous infusion of Ketamine 0.3 to 0.5 mg/kg per hour PCA Dilaudid 2.0-2.5 mg |
|
| Opioid Only | No Intervention | Patient-controlled analgesia Dilaudid 2.0-2.5 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | Low dose continuous infusion of ketamine 0.3 to 0.5 mg/kg per hour |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Enrico Camporesi, MD | University of South Florida | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28853040 | Background | Puri L, Nottage KA, Hankins JS, Anghelescu DL. State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease. Paediatr Drugs. 2018 Feb;20(1):29-42. doi: 10.1007/s40272-017-0263-z. | |
| 23565738 | Background | 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. |
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| ID | Term |
|---|---|
| D006450 | Hemoglobin SC Disease |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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Randomized Controlled Prospective Clinical Trial
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| Nausea and vomiting scores Visual Analog Scale 0 - 10 | Nausea and vomiting scores Visual Analog Scale 0 - 10 | 1-3 hours |
| 16854557 | Background | Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006 Aug;60(7):341-8. doi: 10.1016/j.biopha.2006.06.021. Epub 2006 Jul 5. |
| 21778336 | Background | Aguado D, Abreu M, Benito J, Garcia-Fernandez J, Gomez de Segura IA. Ketamine and remifentanil interactions on the sevoflurane minimum alveolar concentration and acute opioid tolerance in the rat. Anesth Analg. 2011 Sep;113(3):505-12. doi: 10.1213/ANE.0b013e318227517a. Epub 2011 Jul 21. |
| 27599837 | Background | Sun J, Lin H, Feng X, Dong J, Ansong E, Xu X. A comparison of intrathecal magnesium and ketamine in attenuating remifentanil-induced hyperalgesia in rats. BMC Anesthesiol. 2016 Sep 6;16(1):74. doi: 10.1186/s12871-016-0235-9. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |