Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (AKTSS)
Overview
- Phase
- Phase 2
- Intervention
- Ketamine
- Conditions
- Sickle Cell Disease
- Sponsor
- UCSF Benioff Children's Hospital Oakland
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
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.
Intervention: Ketamine
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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))
- 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)
- 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)