Clinical Randomized Controlled Trial Of Hypoxic Pretreatment Relieving Hypoxemia During One Lung Ventilation

OLV （One-lung ventilation） is widely used in thoracic surgery anesthesia, while theimpact of one-lung ventilation on respiratory function equally attracted much attention.When two-lung ventilation converts to OLV, non-ventilation lung collapses withoutairflow but blood perfusion continues, thus ventilation/perfusion imbalance will lead tohypoxemia, which becomes a key factor to the implementation of one-lung ventilation.HPV is pulmonary circulation’s unique compensatory response to hypoxia and thecompensatory protection mechanism to maintain the ventilation/perfusion ratio. DuringOLV when alveolar oxygen pressure goes down to a certain extent, rapid, reversiblepulmonary arteries will emerge and pulmonary vascular resistance will increase, so thatthe flow of blood from the hypoxic area assembles in well-ventilated area, which willreduce blood doping, improve alveolar oxygenation, but until now there is still a lack of aneffective way to enhance the HPV during one-lung ventilation. In animal trails, evidencewas obtained that chronic hypoxia got potential to exaggerate HPV. Based on thoseevidences, we hypothesized that pretreatment with hypoxia may amplify HPV when OLVwas needed, however, whether it will improve hypoxemia during OLV still needexploring.Hypoxemia provokes pulmonary vascular endothelial cell damage, accompanied with higher expression of ET-1. High levels of ET-1targeted at vascular smooth muscle celland seduced free calcium channel open. Intracytoplasm calcium over-loading correlates topulmonary vasoconstriction. Elective ET-1may play a most important part in pulmonaryvasoconstriction based on the fact that ET-1receptor antagonist inhibits HPV. Therefore,further investigation emerges an acquirement in testing relationship between pretreatmentwith hypoxia in moderating meionectic blood and ET-1during OLV.This study carried out a randomly controlled clinical trial to evaluate the impacts ofthe pretreatment of OLV-induced hyoxemia on arterial oxygenation, intrapulmonary shuntand plasma ET-1levels, and explored the feasibility and the mechanism that hypoxicpretreatment improve one-lung ventilation hypoxemia.Methods1. This study chose42ASAⅠ^Ⅱ patients undertaking radical resection ofesophageal carcinoma, including20males and22females respectively who were aged59.4±1.5y and weighed64.6±2.3kg. All patients included had no historical asthma orairway hypersensitivity disease, heart dysfunction, severe hypertension and bronchialintubation contraindication. In presurgical pulmonaryfunctional tests, the measured valuesof FVC and FEV1/FVC were75%higher than the expected values.The42patients were randomly stratified into two groups: the pretreatment group（n=21） and the control group （n=21）. Patients who suffered intraoperative severehyoxemia （SpO₂<85%） were excluded from this study.2. Venous access was established in right upper extremity and ECG（electrocardiograph）, HR （heart rate）, MAP （mean artery pressure） and SpO₂were appliedfor dynamic and continuous monitoring when patients reached operation room. At30minbefore operation, intra-venous scopolamine, tropisetron and dexamethasone were given ata dose of0.3mg,2mg and10mg respectively. Right radical artery intubation was finishedunder locoregional anesthesia, and then connected to FloTrac sensor for non-intermittentmonitoring. General anesthesia induction was consisted of midazolam0.05mg/kg,propofol2mg/kg, rocuronium0.8mg/kg and fentanyl2μg/kg. Left bronchial catheter was intubated after rocuronium took effects（F=35³9）. The end of bronchial catheter outermouth was connected to anesthesia machine for IPPV （intermittent positive pressureventilation）. Then confirm bronchial catheter properly with fiber bronchoscopy.Ventilation parameters was adopted as VT （ventilation volume）8ml/kg, RR （respiratoryrate）12times per minute, I: E （inspiration and expiration ratio）1:2, FiO₂（fraction ofinspired oxygen）1.0and oxygen flow1L/min. The position of bronchial catheter wasconfirmed again after right arm recumbent posed on surgical patient with fiberbronchoscopy. During anesthesia of the surgery, P_ETCO₂was maintained between35and45mmHg and BIS40to65, with tactics of continuously intra-venous infusion of propofolat4⁸mg/kg/h and remifentanyl at0.1⁰.2μg/kg/min and cis-atracurium intermittentlygiven according to TOF （train of four）. Bronchial catheter removal was accomplished byanesthesiologist in PACU （post-anesthesia care unit）.3. In the pretreatment group, the left bronchial catheter was kept to be clamped andthe right part was ventilated5min after right arm recumbent posted before thoracotomy,with regular ventilation parameters. Then the outer terminal of left bronchial catheter wasshut after connecting to vacuum extractor and attracted for15sec at-20Kpa. A model ofpretreatment with hypoxia and OLV was set up.15min later the patient was converted toTLV （Two-lung ventilation）. The control group kept Two-lung ventilation all time alongwith the above ventilation parameters. With prior ventilation parameters, afterthoracotomy, both groups were ventilated by one lung.4. In both groups, artery blood was collected for blood gas analysis at T₀（30minbefore anesthesia）, T₁（End of pretreatment）, T₂（Opening the pleura）, T3（15min afterOLV）, T₄（30min after OLV）, T₅（60min after OLV）, and T₆（90min after OLV）. Simplifiedformula was used for evaluating pulmonary shunt: Qs/Qt=（700-PaO₂）×100%×5%（FiO₂=1.0, PaO₂recorded with mmHg）. Meanwhile,2ml venous blood was collected fordetecting ET-1secretion with ELISA analysis at T₁,T₂, T₃,T₄,T₅and T₆;at the same time,HR, MAP, SpO₂, CO （cardiac output）, peak pressure and mean pressure of airway are alsorecorded. After the operation, volume of input and output, total operational time （includingOLV） were counted. Results1. The level of PaO₂in both groups showed a significant decrease after OLV comparedwith that during TLV （P<0.05）. Patients in the control group had much less PaO₂thanthose in the pretreatment group at each testing time （P<0.05）.2. Qs／Qt ratio climbed much higher after OLV adopted in both two groups, thepretreatment group experienced a smaller downward ratio than the control group at eachtesting time, but at15min the distinction reached a remarkable difference （P<0.05）.3. The density of Detected ET-1after OLV was far higher than that during TLV in boththe pretreatment group and the control group, but its density in the pretreatment groupincreased comparing with control group at each testing time, and the distinction reached aremarkable difference at15min during OLV（P<0.05）.Conclusion: Pretreatment with hypoxia could reduce propensity of meionectic blood andpulmonary shunt during OLV. Its mechanism may be related to increasing plasma ET-1levels and enhancing hypoxic pulmonary vasoconstriction...