Morphine Clearance and Glomerular Filtration in Sickle Cell Patients in Crisis in Intensive Care
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 10
- 主要终点
- Therapeutic failure
研究概览
简要总结
Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. These crisis (acute vaso-occlusive crisis) require strong treatment based on morphine, and often require intensive care.However, treatment is often insufficiently effective. Patient can also experiment acute chest syndrome, a complication of vaso-occlusive crisis, which can be responsible for respiratory failure. In addition, patients with sickle cell disease frequently have kidney damage called sickle cell nephropathy, which in the early stages of the disease is responsible for renal hyperfiltration, meaning that the kidneys filter the blood more than necessary, with faster elimination of drugs. For example, it is known that higher doses of antibiotics must be used in these patients than in the general population for the same effectiveness. The hypothesis of the study is that morphine, a drug eliminated by kidneys, is underdosed in patients with sickle cell disease, which is responsible for the difficulties in achieving sufficient analgesia.
Objective: To determine the glomerular filtration rate threshold for which it is necessary to prescribe higher doses of morphine in sickle cell patients with vaso-occlusive crisis.
Methods: inclusion of 100 patients admitted to intensive care for an acute vaso-occlusive crisis or acute chest syndrome and receiving morphine. Within 24 hours of study inclusion, four morphine dosages will be performed, in parallel with a precise determination of the glomerular filtration rate by measuring the elimination rate of a tracer, 100% eliminated by the kidneys and injected at the start of the study. This tracer is iohexol, a contrast agent commonly used in radiology. Morphine underdosage will be interpretated regarding glomerular filtration rate. The effectiveness of analgesia and the amount of analgesics required will be also be analyzed.
Outlook: At the end of this study, the investigators will be able to offer adapted doses of morphine for sickle cell patients in crisis, adapted to glomerular filtration rate, in the aim of personalizing analgesia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥ 18 years old
- •Known homozygous sickle cell disease SS, SC, S-beta+, or S-beta0
- •Admitted in an intensive care unit
- •Clinical diagnosis of vaso-occlusive crisis and/or acute chest syndrome
- •Receiving PCA treatment with morphine
- •Patient's consent for study participation and/or from a relative if case of patient's incapacity
- •Affiliation to social protection
排除标准
- •Patient previously included in the study during a previous stay
- •Injection of iodinated contrast medium outside the scope of the study within 24 hours prior to inclusion, or scheduled within 9 hours following the scheduled time of iohexol injection
- •Contraindication to iohexol: known or suspected immediate or delayed hypersensitivity, thyrotoxicosis.
- •Patient undergoing morphine treatment or substitution treatment such as methadone or buprenorphine prior to hospitalization (having received morphine or a derivative regardless of the route of administration in the week prior to hospitalization).
- •Chronic liver disease likely to interfere with morphine metabolism (cirrhosis )
- •Any condition that contraindicates the use of morphine according to the summary of product characteristics
- •Patients under legal protection
- •Pregnant or breastfeeding women
- •Exclusion criteria :
- •Need for extrarenal epuration within 24 hours of inclusion
研究组 & 干预措施
Determination of glomerular filtration rate by Iohexol
Four morphine dosages, and a precise determination of the glomerular filtration rate by the measure of the elimination rate of iohexol will be carried out. The investigators will analyse in which patients and for which glomerular filtration rate there is morphine underdosage and simultaneously evaluate the effectiveness of analgesia and the amount of analgesics required.
干预措施: Injection of iohexol for glomerular filtration rate (GFR) measurement (Drug)
结局指标
主要结局
Therapeutic failure
时间窗: 24 hours
Prediction of therapeutic failure based on glomerular filtration rate according to the CKD-EPI formula (area under roc curve). Therapeutic failure is defined as a percentage of relief assessed by the verbal numerical scale not reaching 30% within 24 hours.
Glomerular filtration rate according to the CKD-EPI formula
时间窗: 5 minutes
Glomerular filtration rate according to the CKD-EPI formula
次要结局
- Clearance of morphine and its metabolites M3G and M6G(24 hours)
- Morphine dose administered(24 hours)
- Morphine dose administred(Day 7)
- Pain progression using the Visual Analog Scale(Every 4 hours for the first 7 days)
- Pain progression using a Numeric Rating Scale(Every 4 hours for the first 7 days)
- Patient Global Impression of Change (PGIC) Over the First 7 Days(Daily, every 24 hours, from Day 1 to Day 7)
- Number of patients receiving paracetamol, nefopam, ketamine, NSAIDs, or nitrous oxide (MEOPA) within 24 hours(24 hours)
- Adverse effects of morphine(Day 7)
- Glomerular filtration rate according to the CKD-EPI formula(5 minutes)
- Plasma clearance of iohexol(5 minutes, 1 hour et 9 hours)