The Effects of Hyperoxia on Organ Dysfunction and Outcome in Critically Ill Patients With SIRS
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Daily Delta Sequential Organ Failure Assessment Score
研究概览
简要总结
Objectives:
- To study the short- and long-term effect of two different PaO2 targets on circulatory status, organ dysfunction and outcome in patient admitted to the ICU with Systemic Inflammatory Response Syndrome (SIRS) criteria.
- To study underlying mechanisms of hyperoxia by determining differences in oxidative stress response between the hyperoxic and the normoxic patients.
Study design:
Randomized, prospective multicentre clinical trial
Study population:
Patients admitted to the Intensive Care unit with ≥ 2 positive SIRS-criteria and an expected ICU stay of more than 48 hours
Intervention:
Group 1: target PaO2 120 (105 - 135) mmHg (high-normal)
Group 2: target PaO2 75 (60 - 90) mmHg (low-normal)
Primary endpoints:
The primary endpoint will be cumulative daily delta SOFA score (CDDS) from day 1 to day 14.
详细描述
Rationale:
Contrary to hypoxia, many physicians do not consider hyperoxia harmful for their patients. To prevent hypoxia, superfluous administration of oxygen is common practice, and hyperoxia is seen in many patients, especially on Intensive Care units. However, an increasing number of studies not only confirm the known negative pulmonary effects of chronic oxygen oversupply, but also important and more acute circulatory effects, characterised by decreased cardiac output (CO), increased systemic vascular resistance (SVR), and impaired microvascular perfusion. These phenomena can impair perfusion of organs, which may outweigh higher arterial oxygen content, resulting in a net loss of oxygen delivery and perturbed organ function. This may for example be responsible for hyperoxia-associated increased infarct size and increased mortality after myocardial infarction and cardiac arrest. The underlying mechanisms are not clarified yet, but probably involve increased oxidative stress with systemic vasoconstriction.
On the other hand, hyperoxia can also induce several favourable effects. The majority of ICU-patients have a systemic inflammatory response syndrome (SIRS) with concomitant vasoplegia due to trauma, sepsis or ischemia/reperfusion injury. Vasoconstriction could benefit these patients with severe SIRS, reducing the need for intravenous volume resuscitation and vasopressor requirements. Furthermore, hyperoxia may exert a preconditioning effect in patients with ischemia/reperfusion injury and prevent new infections due to its antibacterial properties.
Hypothesis:
Hyperoxia during SIRS ultimately has unfavourable effects on organ function, especially on a longer term.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 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
- •≥2 positive SIRS-criteria:
- •Temperature >38 deg.C or hypothermia <36 deg.C
- •Heart rate >90 bpm
- •Respiratory rate >20 /min or pCO2 <32 mmHg (4.3 kPa)
- •Number of leucocytes >12 x 10^9/l of <4 x 10^9/l of >10% bands
- •Within 12 hours of admittance to the ICU
- •Expected stay of more than 48 hours as estimated by the attending physician
排除标准
- •Elective surgery
- •Carbon monoxide poisoning
- •Cyanide intoxication
- •Methemoglobinemia
- •Sickle cell anemia
- •Severe pulmonary arterial hypertension (WHO class III or IV)
- •Known severe Acute Respiratory Distress Syndrome (ARDS) (PaO2/FiO2 ≤100 mmHg and PEEP ≥ 5 cm H2O)
- •Known cardiac right to left shunting
- •Pregnancy
- •Severe Chronic Obstructive Pulmonary Disease (COPD) (Gold class III or IV) or other severe chronic pulmonary disease
- •Patients participating in other interventional trials
研究组 & 干预措施
High-normal PaO2
In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a PaO2 of 120 mmHg (16 kPa), range 105-135 mmHg (14-18 kPa).
干预措施: Oxygen (Drug)
Low-normal PaO2
In patients requiring respiratory monitoring, supplemental oxygen is titrated to achieve a target PaO2 of 75 mmHg (10 kPa), range 60-90 mmHg (8-18 kPa).
干预措施: Oxygen (Drug)
结局指标
主要结局
Daily Delta Sequential Organ Failure Assessment Score
时间窗: 14 days
The primary endpoint will be cumulative daily delta SOFA score (CDDS) from day 1 to day 14, calculated as the sum of \[daily SOFA score minus admission SOFA score\] from day 2 to day 14. Daily SOFA score is calculated as the total of maximum scores for each organ system excluding respiratory system (because of possible PaO2/FiO2 distortion). For patients discharged from the ICU, SOFA score will be registered as 0 from the day of discharge to day 14. Death in the ICU will be registered as a score of 20 (maximum) from the day of death to day 14.
次要结局
- total maximum SOFA score minus SOFA score on admission(14 days)
- Microcirculatory flow index and Perfused vessel density(14 days)
- Mortality(14 days, in-ICU (max 90 days), in-hospital (max 90 days))
- Vasopressor / Inotrope requirements(14 days)
- Oxidative stress (F2-isoprostanes)(days 1, 3, 7)
- Length of stay (hospital)(average expected 10 to 28 days)
- Renal function, fluid balance(14 days)
- SOFA rate of decline(14 days)
- Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline(14 days)
- Hypoxic events (PaO2 <55 mmHg)(14 days)
- Duration of mechanical ventilation and ventilator-free days(14 days)
- Systemic Vascular Resistance Index(14 days)
- Cardiac Index(14 days)
- Length of stay (ICU)(average expected 2 to 28 days)
研究者
Angelique Spoelstra-de Man
Consultant Intensivist
Amsterdam UMC, location VUmc