Haemodynamic Effects of Paracetamol (Acetaminophen) as Extended Intravenous Infusion Versus Intravenous Bolus in Septic Shock Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- The incidence of hypotension .
研究概览
简要总结
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as sepsis that has circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone. Clinically, this includes patients who fulfill the criteria for sepsis who, despite adequate fluid resuscitation, require vasopressors to maintain a mean arterial pressure ≥65 mmHg and have a lactate >2 mmol/L (>18 mg/dL). Feve is a common sign of infection in septic shock critically ill patients. Many critically ill patients experience pain. Paracetamol is considered safe and currently one of the most common antipyretics and used as part of multimodal analgesia for acute pain in the intensive care unit. According to the company's product information leaflet, the rate of hypotension complicating intravenous paracetamol treatment ranges from 0.01 to 0.1%. However, recent studies reported a much higher incidence and may be harmful in critically ill adults. The hemodynamic effects of intravenous (IV) paracetamol are unknown in septic shock patients, that the most vulnerable population and hemodynamically unstable.
The aim of this study is to assess the incidence of hypotension of the extended intravenous paracetamol (acetaminophen) infusion over three hours in comparing with intravenous paracetamol bolus over 15 minutes in hemodynamically unstable patients (septic shock).
详细描述
Sepsis, inflammatory response to infection, contributes directly or indirectly to mortality in the majority of critically ill patients. An elevated cardiac index and a decreased systemic vascular resistance leading to hypotension and hypoperfusion of vital organs characterize the early stage of septic shock. The hypotensive state is often not amenable to fluid resuscitation alone and requires institution of vasoactive agents to counter the profound fall in systemic vascular resistance, which is an integral feature of septic shock .
Acetaminophen is the antipyretic and analgesic that is most often given to hospitalized patients, including those in critical care units. The mechanism of action of acetaminophen remains incompletely understood, but the antipyretic response appears to be due to blocking cyclooxygenase-II and inhibiting prostaglandin-II synthesis in the central nervous system.
Intravenous (IV) acetaminophen has gained popularity for inpatient management of acute pain for its practical and clinical advantages. IV administration is associated with more predictable pharmacokinetic performance compared with rectal (30%-40% bioavailability) and oral dosage forms of acetaminophen (60%-70% bioavailability).
Predictable kinetics as well as ease of IV administration has made it an especially attractive option in the critically ill patients who have altered gut absorption secondary to numerous pathophysiological and therapeutic influences .
IV acetaminophen has shown promise in improving patient satisfaction, managing fever, and decreasing postoperative opioid requirements. These features have made it one of the most widely ordered medications within critical care and surgical services.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age adult ≥ 18 years old.
- •The patient fulfills the criteria of septic shock definition:
- •Sepsis needs vasopressor therapy.
- •Serum lactate level greater than 2 mmol/l (SSC 2016).
- •Patient with contractility greater than 40%
排除标准
- •paracetamol hypersensitivity or allergy.
- •Acute liver injury or failure
- •Childs-Pugh C liver disease
- •Heat stroke.
- •Malignant hyperthermia.
- •Neuroleptic Malignant Syndrome.
- •Continous renal replacement therapy.
- •Ventricular assist device.
- •Around-the-clock scheduled of acetaminophen-containing medications administration or non-steroidal anti-inflammatory drugs.
- •Pregnancy/lactation.
研究组 & 干预措施
Placebo group
placebo group (100 ml normal saline over 15 minutes)
干预措施: Normal saline (Drug)
bolus group
bolus group (1000mg/100 ml paracetamol over 15 minutes)
干预措施: Paracetamol (Drug)
Extended infusion group
Extended infusion (1000mg/100 ml paracetamol over 3 hours)
干预措施: Paracetamol (Drug)
结局指标
主要结局
The incidence of hypotension .
时间窗: pre intervention and six hours after the intervantion
defined as a decrease in SBP ≥ 20٪ from baseline, by extended infusion of intravenous paracetamol
次要结局
- The changes in hemodynamic parameters(pre intervention and six hours after the intervantion)
- The changes in temperature(pre intervention and six hours after the intervantion)
- The changes in vassopresors and fluid bolus(pre intervention and six hours after the intervantion)
研究者
Ayah Mohammed Khalil
Principal Investigator, Senior clinical pharmacist in Department of Clinical Pharmacy, Cairo University Hospitals (Kasr alainy), Cairo, Egypt.
Al-Azhar University
