Investigation of the Anti-inflammatory Effect of Ketamine in Cardiac Surgery : Randomızed Controlled Trıal
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 177
- 试验地点
- 1
- 主要终点
- Change in Neutrophil-to-Lymphocyte Ratio (NLR)
研究概览
简要总结
Background:
The inflammatory response following cardiac surgery is known to contribute significantly to morbidity and mortality. Neutrophils and inflammatory mediators play a critical role in the pathogenesis of postoperative complications. The aim of this study was to evaluate the effect of intraoperative ketamine administration on the inflammatory response in patients undergoing cardiac surgery using routinely employed immuno-inflammatory parameters in clinical practice.
Methods:
After randomization, patients were divided into two groups: the ketamine group and the control group. Following admission to the operating room, standard monitoring and anesthesia induction were performed. In addition to the control group, patients in the ketamine group received 1 mg/kg ketamine during induction and a continuous intravenous infusion of 2.4 mg/kg/h ketamine for maintenance.
Immuno-inflammatory parameters were assessed using routine blood tests obtained preoperatively and on postoperative day 1. These parameters included leukocyte, neutrophil, lymphocyte, and platelet counts; neutrophil-to-lymphocyte ratio (NLR); platelet-to-lymphocyte ratio (PLR); NLR index; delta NLR; ΔPLR; PLR index; systemic inflammatory response index (SIRI); systemic immune-inflammation index (SII); and C-reactive protein (CRP), ΔCRP, and CRP index. In addition, patients' pain scores within the first 24 hours following postoperative extubation, as well as hospital mortality and morbidity rates, were evaluated.
详细描述
Participants and Study Design We conducted a single-center, randomized, controlled, single-blind clinical study including patients scheduled for cardiac surgery. Patients aged 18-80 years who were able to provide informed consent and reliably communicate their symptoms to the research team, and who were scheduled for elective cardiac surgery, were included in the study.
Patients were excluded if they had contraindications to anesthesia; cognitive impairment or communication barriers; end-stage renal failure (receiving routine hemodialysis); pregnancy or lactation; a known history of ketamine allergy; ejection fraction (EF) <35%; planned emergency or reoperation; arrhythmia; morbid obesity; psychiatric disorders; hepatic failure; use of anti-inflammatory medications; preoperative white blood cell count (leukocyte) ≥15 × 10³/µL; C-reactive protein (CRP) ≥30 mg/L; or refusal to participate in the study.
A total of 177 patients scheduled for cardiac surgery at Necmettin Erbakan University Meram Faculty of Medicine Hospital were enrolled between October 30, 2022, and March 30, 2023. Eleven patients were excluded due to surgical cancellation and data loss. Six patients who died intraoperatively or within the first 24 hours postoperatively were excluded from biomarker analyses due to unavailable postoperative measurements; however, these patients were included in the mortality analysis. A total of 160 patients with complete postoperative data were included in the primary biomarker analysis. Patients were randomly assigned to either the ketamine group or the control group, with 80 patients in each group.
Randomization Patients were randomized using the closed opaque envelope method by a researcher who was not involved in study coordination or data collection.
Anesthesia Protocol In the operating room, patients received intravenous (IV) premedication with 1 mg midazolam and 50 µg fentanyl. Standard noninvasive monitoring (electrocardiogram and peripheral oxygen saturation) was applied to all patients. Under local anesthesia, the radial artery was cannulated with a 20 G catheter, and invasive arterial blood pressure monitoring was initiated. Hemodynamic data were recorded using invasive measurements. Drug doses were calculated based on adjusted body weight.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-80 years.
- •Scheduled to undergo elective cardiac surgery.
- •Able to provide informed consent.
- •Able to reliably communicate symptoms to the research team.
排除标准
- •Contraindications to anesthesia.
- •Cognitive impairment or communication barriers.
- •End-stage renal failure (receiving routine hemodialysis).
- •Pregnancy or breastfeeding.
- •Known allergy to ketamine.
- •Ejection fraction (EF) <35%.
- •Emergency or repeat surgery.
- •Arrhythmia.
- •Morbid obesity.
- •Psychiatric disorders.
- •Hepatic failure.
- •Use of anti-inflammatory medications.
- •Preoperative white blood cell count (leukocyte) ≥15 × 10³/µL.
- •C-reactive protein (CRP) ≥30 mg/L.
- •Declined to participate in the study
研究组 & 干预措施
ketamine group
In addition to standard treatment, ketamine was administered at a dose of 1 mg/kg during induction and as a continuous infusion at 2.4 mg/kg/h
干预措施: ketamine (Drug)
control group
Standard treatment was administered to all patients.
结局指标
主要结局
Change in Neutrophil-to-Lymphocyte Ratio (NLR)
时间窗: Preoperative to postoperative day 1 (within 24 hours)
Neutrophil-to-lymphocyte ratio (NLR), expressed as a dimensionless ratio, calculated as neutrophil count divided by lymphocyte count, evaluated as postoperative minus preoperative values.
Systemic Immune-Inflammation Index (SII)
时间窗: Preoperative and postoperative day 1
Systemic Immune-Inflammation Index (SII), expressed as an index value, calculated as platelet count × neutrophil count divided by lymphocyte count.
Systemic Inflammatory Response Index (SIRI)
时间窗: Preoperative and postoperative day 1
Systemic Inflammatory Response Index (SIRI), expressed as an index value, calculated as neutrophil count × monocyte count divided by lymphocyte count.
Change in Platelet-to-Lymphocyte Ratio (PLR)
时间窗: Preoperative to postoperative day 1
Platelet-to-lymphocyte ratio (PLR), expressed as a dimensionless ratio, calculated as platelet count divided by lymphocyte count, evaluated as postoperative minus preoperative values.
Change in C-Reactive Protein (CRP)
时间窗: Preoperative to postoperative day 1 (within 24 hours)
Serum C-reactive protein (CRP) levels measured in mg/L, assessed preoperatively and on postoperative day 1, expressed as postoperative minus preoperative values.
Change in Neutrophil Count
时间窗: Preoperative to postoperative day 1 (within 24 hours)
Neutrophil count measured in 10³/µL, assessed preoperatively and on postoperative day 1, expressed as the change between measurements.
Change in Lymphocyte Count
时间窗: Preoperative to postoperative day 1 (within 24 hours)
Lymphocyte count measured in 10³/µL, assessed preoperatively and on postoperative day 1.
Change in Platelet Count
时间窗: Preoperative to postoperative day 1 (within 24 hours)
Platelet count measured in 10³/µL, assessed preoperatively and on postoperative day 1.
NLR Index
时间窗: Postoperative day 1
NLR index calculated as postoperative NLR divided by preoperative NLR, expressed as a ratio.
PLR Index
时间窗: Postoperative day 1
PLR index calculated as postoperative PLR divided by preoperative PLR, expressed as a ratio.
CRP Index
时间窗: Postoperative day 1
CRP index calculated as postoperative CRP divided by preoperative CRP.
Delta NLR
时间窗: Postoperative day 1
Delta NLR calculated as postoperative NLR minus preoperative NLR.
Delta PLR
时间窗: Postoperative day 1
Delta PLR calculated as postoperative PLR minus preoperative PLR.
Delta CRP
时间窗: Postoperative day 1
Delta CRP calculated as postoperative CRP minus preoperative CRP.
次要结局
- Extubation Time(From the end of surgery to tracheal extubation, within 48 hours postoperatively)
- Length of ICU Stay(From ICU admission to ICU discharge (up to 28 days))
- Length of Hospital Stay(From the date of surgery to hospital discharge (up to 28 days))
- Postoperative Pain Score (NRS)(First 24 hours after extubation)
- 28-day Mortality(28 days postoperative)
- Analgesic Consumption(First 24 hours after extubation)
- Vasoactive Inotropic Score (VIS)(Intraoperative period (from induction to end of surgery))
- Patient Satisfaction and Pain Assessment (Prince Henry Hospital Pain Score, PHHPS)(Within the first 24 hours after extubation)
研究者
turgay atay
Principal Investigator-medical doctor
Konya City Hospital