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临床试验/NCT03450746
NCT03450746已完成不适用

Metabolic and Physiological Changes During Minor Orthopaedic Surgery in Otherwise Healthy Patients

Aalborg University Hospital1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2017年11月2日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
15
试验地点
1
主要终点
Metabolites in exhaled breath condensate and in arterial blood

研究概览

简要总结

The air we breathe contains 21% of oxygen. Oxygen is vital for the cells ability to produce energy and without it we could not survive. Oxygen normally exists as a molecule consisting of two atoms, O2. It has two unpaired electrons and thus is unstable and willing to accept electrons to become stable. During the formation of ATP a transportation of electrons happens over the inner membrane of the mitochondria's. Oxygen can accept these and is thereby reduced to water. Normally about 4% is not fully reduced and instead produces superoxide. Superoxide is transformed to hydrogen peroxide by superoxide dismutase (SOD) and then into oxygen and water by catalase and glutathione peroxidase. It is also possible for hydrogen peroxide to be converted to hydroxyl radicals by Fenton reactions. All these radicals are called reactive oxygen species (ROS) and they are highly reactive and capable to induce damage to cellular components as proteins, DNA and lipids. Under normal conditions SOD, catalase and glutathione peroxidase work as anti-oxidative compounds to prevent oxidative stress and damage. However, under hyperoxic conditions these defences can be overwhelmed, resulting in the formation of excess ROS and thus oxidative damage.

During general anaesthesia the use of supplemental oxygen to avoid life-threatening hypoxaemia has been common practice for many years and a fixed fraction of inspired oxygen (FiO2) ranging from 0.3 to 1.0 is often used. This lead to supranormal levels of oxygen in the lungs and most of the patients also have supranormal levels of partial pressure of arterial oxygen in their blood.

This study will examine otherwise healthy ambulant patients undergoing minor orthopaedic surgery during general anaesthesia to elucidate metabolic and physiological changes caused by ventilation with FiO2 0.50 for at least 45 minutes using standard respiratory settings. Exhaled breath condensate (EBC) and arterial blood will be collected prior to and after surgery. The two EBCs and two blood samples will be stored at -80°C for analysis after all patients have been included. The metabolic changes will be measured with NMR technique and multivariate statistical analysis comparing baseline values with values obtained after oxygen exposure.

Collapse of the small airways induced by anaesthesia and FiO2 will be evaluated by measuring resistance and reactance with airway oscillometry after surgery compared to a baseline measurement before surgery.

详细描述

Oxygen supplement during general anaesthesia During general anaesthesia the use of supplemental oxygen to avoid life-threatening hypoxaemia has been common practice for many years. This lead to supranormal levels of oxygen in the lungs (hyperoxia) and most patients also have supranormal levels of partial pressure of arterial oxygen (PaO2) in their blood (hyperoxaemia). The same iatrogen hyperoxia is also common in mechanically ventilated patients in the intensive care unit. Is seems to be forgotten that supplemental oxygen is a medicine and like all medication it should not be administered in excess.

During general anaesthesia a fixed fraction of inspired oxygen ranging from 0.3 to 1.0 is often used. Patients are monitored with continuously measurement of peripheral oxygen saturation and if this is low or an arterial gas shows low PaO2 then FiO2 is further increased. However, a decrease beyond the prefixed FiO2 is seldom done even if oxygen saturation is 100% or the arterial gas shows a high PaO2.

More and more evidence question the safety of this liberal use of hyperoxia as high oxygen supplement and the formation of ROS can lead to cell dysfunction and thereby contribute to pulmonary dysfunction postoperatively.

Adverse effects of oxygen FiO2 exceeding the atmospheric content of 0.21 can have direct toxic effects on lung tissue especially for FiO2 exceeding 0.60. Studies from the 1970's showed that when breathing FiO2 1.0 for more than four hours people experienced mild symptoms like tracheobronchitis and pleuritic. This is a mild irritation behind the sternum, in the airways or in the lungs. This discomfort is aggravated by deep inspiration and can cause cough. They also showed that a high FiO2 of 0.95-1.0 given for several days lead to pulmonary edema and eventually lung fibrosis. High FiO2 also induce collapse of lung areas leading to pulmonary shunt because of reabsorption atelectasis and induce pulmonary vasodilatation but otherwise induce vasoconstriction in all others vascular beds (except in uterus) and thereby reduce cardiac output and end organ perfusion.

The precise mechanism of the direct cellular damage and vasoconstriction is unknown but is believed to be due to increased production of ROS5.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Over the age of 18 years
  • Otherwise healthy (No major illness and not taking any medicine on a regular basis)
  • Non-smoker (Have never smoked or stopped smoking two years or more before the trial date)
  • Have given informed consent

排除标准

  • Any respiratory infection in the past three months leading to consulting a doctor (Any infection in the lungs or the airways in the three months leading up to the trial that resulted in the participant consulting a doctor or taking any medication for the infection)
  • Any alcohol intake the last 24 hours (Drinking any alcohol in the last 24 hours up to the start of the trial)
  • Pregnancy (Confirmed by positive urine human gonadotropin (hCG) or plasma-hCG)

结局指标

主要结局

Metabolites in exhaled breath condensate and in arterial blood

时间窗: minor surgery (approximately 45-120 minutes)

Metabolites measured by Nuclear Magnetic Resonance spectroscopy (NMR), explanatory study thus every changes in metabolites will be visualized

次要结局

  • Minor airway resistance(minor surgery (approximately 45-120 minutes))
  • Airway reactance(minor surgery (approximately 45-120 minutes))
  • heart rate(minor surgery (approximately 45-120 minutes))
  • Mean arterial bloodpressure(minor surgery (approximately 45-120 minutes))
  • oxygen saturation(minor surgery (approximately 45-120 minutes))
  • Partial pressure of arterial oxygen(minor surgery (approximately 45-120 minutes))

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Bodil Steen Rasmussen

Professor

Aalborg University Hospital

研究点 (1)

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