Optimal Oxygenation in the Intensive Care Unit
キーワード
概要
説明
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.
Objectives:
1. To study the short- and long-term effect of two different PaO2 targets on circulatory status, organ dysfunction and outcome.
2. 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:
We will investigate 2 groups with PaO2 targets both within the range of current practice
Group 1: target PaO2 120 (105 - 135) mmHg (high-normal)
Group 2: target PaO2 75 (60 - 90) mmHg (low-normal)
日付
| 最終確認済み: | 03/31/2019 |
| 最初に提出された: | 12/08/2014 |
| 提出された推定登録数: | 12/14/2014 |
| 最初の投稿: | 12/21/2014 |
| 最終更新が送信されました: | 04/24/2019 |
| 最終更新日: | 04/25/2019 |
| 実際の研究開始日: | 01/31/2015 |
| 一次完了予定日: | 03/31/2019 |
| 研究完了予定日: | 11/30/2019 |
状態または病気
介入/治療
Drug: Oxygen
段階
アームグループ
| 腕 | 介入/治療 |
|---|---|
| Active Comparator: 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). | |
| Active Comparator: 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). |
適格基準
| 研究の対象となる年齢 | 18 Years に 18 Years |
| 研究に適格な性別 | All |
| 健康なボランティアを受け入れる | はい |
| 基準 | Inclusion Criteria: - ≥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 Exclusion Criteria: - 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 |
結果
主な結果の測定
1. Daily Delta Sequential Organ Failure Assessment Score [14 days]
二次的な結果の測定
1. total maximum SOFA score minus SOFA score on admission [14 days]
2. SOFA rate of decline [14 days]
3. Total maximum SOFA score, total maximum SOFA score minus SOFA score on admission, SOFA rate of decline [14 days]
4. Mortality [14 days, in-ICU (max 90 days), in-hospital (max 90 days)]
5. Hypoxic events (PaO2 <55 mmHg) [14 days]
6. Vasopressor / Inotrope requirements [14 days]
7. Renal function, fluid balance [14 days]
8. Oxidative stress (F2-isoprostanes) [days 1, 3, 7]
9. Duration of mechanical ventilation and ventilator-free days [14 days]
10. Length of stay (ICU) [average expected 2 to 28 days]
11. Length of stay (hospital) [average expected 10 to 28 days]
12. Systemic Vascular Resistance Index [14 days]
13. Cardiac Index [14 days]
14. Microcirculatory flow index and Perfused vessel density [14 days]
