Effect Of Ciprofol On Inflammatory Response And Oxidative Stress In Patients Undergoing Lobectomy

BackgroundAccording to statistics,the incidence of lung cancer is increasing year by year and has become the malignant tumor with the second highest incidence and the first highest mortality ratethe worldwide.Lung cancer is often treated by lobectomy in the early stage,and intraoperative one-lung ventilation（OLV）is often used to meet the surgical demand.The mechanical injury,inflammatory response,oxidative stress and ischemia-hypoxia-reperfusion injury caused by OLV can lead to a significant increase in the incidence of postoperative pulmonary complications（PPCs）in patients.Anesthetic drugs with pulmonary protective effects can be selected clinically to reduce perioperative inflammatory responses and oxidative stress,thereby reducing the incidence of PPCs.Propofol has been widely used clinically and has been shown to be pulmonoprotective during mechanical ventilation by reducing inflammatory responses and oxidative stress through multiple mechanisms.Ciprofol is a new intravenous anesthetic drug that entered the clinic in December 2020,which is based on the chemical structure of propofol with the introduction of cyclopropyl to form a chiral structure,increasing the steric effect and improving the affinity with Gamma aminobutyric acid type A receptor,which is about 5 times that of propofol.Ciprofol and propofol have similar safety and efficacy in general anesthesia,but ciprofol is more capable of maintaining hemodynamic stability,reducing the incidence of adverse events such as intubation reactions and hypotension,and providing a more stable level of sedation.And while ciprofol has been shown to protect cardiomyocytes by exerting anti-inflammatory,anti-oxidative stress and anti-apoptotic effects,no studies on the pulmonary protective effects of ciprofol have been seen.On the basis that ciprofol has a similar mechanism of action to propofol and is superior to propofol in terms of potency and clinical performance,it is inferred that ciprofol may have a superior pulmonary protective effect to propofol.ObjectiveTo evaluate the pulmonary protective effect of ciprofol by studying the effects of propofol and ciprofol on the inflammatory response,oxidative stress,pulmonary function,incidence of PPCs and perioperative adverse effects in patients undergoing thoracoscopic lobectomy,and to provide a reference for the selection of anesthetic drugs for pulmonary resection.MethodsThis study was a prospective randomized controlled clinical trial.70 patients undergoing elective thoracoscopic lobectomy were recruited at our institution from October 2021 to August 2022,and 30patients were finally included in each group according to the inclusion,exclusion and exclusion criteria.（1）Anesthesia protocol（1）Induction of anesthesia:Propofol 1.5～2.5 mg/kg in group B and ciprofol 0.4～0.6 mg/kg in group H.In addition,the same induction regimen was used in each group;（2）Anesthesia maintenance:Propofol 4～6 mg·kg^-1 h^-1 in group B and ciprofol 0.8～1.2 mg·kg^-1·h^-1 in group H.In addition,the same maintenance regimen was used in each group;（2）Observation indexes（1）Hemodynamic indexes:Heart rate（HR）and invasive mean arterial pressure（MAP）were recorded at the time of admission（T₀）,immediately before intubation（T₁）,immediately after intubation（T₂）,5 min after intubation（T₃）,1 h after OLV（T₄）,and 15 min after resumption of bilateral lung ventilation（T₅）.（2）Inflammatory and oxidative stress indicators:Serum interleukin-6（IL-6）,interleukin-8（IL-8）,interleukin-10（IL-10）,tumor necrosis factor-α（Tumor necrosis factor-α）were measured at T₀,T₄,T₅,24 h postoperatively（T₆）and 48 h postoperatively（T₇）.Serum malondialdehyde（MDA）and superoxide dismutase（SOD）were measured at T₀,T₄ and T₅;（3）Pulmonary function index:Blood gas analysis was performed at T₀,T₄ and T₅,and the alveolar gas-arterial oxygen partial pressure difference（A-a DO₂）was measured,and the Oxygenation index（OI）was calculated,OI=Alveolar oxygen partial pressure/Fraction of inspiration oxygen;At T₂,T₄ and T₅,dynamic lung compliance（Cdyn）=VT/（airway platform pressure-Positive end expiratory pressure）was calculated;（4）Incidence of PPCs:Follow-up by evaluators unaware of the subgroup and the number of patients in both groups presenting with PPCs in the first 7 days after surgery was collected;（5）Perioperative adverse effects:Injection site pain,intraoperative hypotension（MAP<80%of baseline level）,intraoperative hypertension（MAP>120%of baseline level）,intraoperative arrhythmias,postoperative delirium,and postoperative death.Results（1）Hemodynamic indexes:At the moment of T₁,MAP was significantly higher in group H than in group B（P<0.05）,and in the comparison of the remaining moments,the difference was not statistically significant（P>0.05）.In the intra-group comparison of MAP,there was no statistically significant difference between T₀ and T₂ and T₃ moments and between T₄ and T₅ moments in group B（P>0.05）,and no statistically significant difference between T₀ and T₃ moments and between T₁ and T₄ and T₅ moments in group H（P>0.05）.The differences were statistically significant（P<0.05）when the remaining moments were compared between the two.（2）Inflammatory response indexes:At the moments of T₆ and T₇,the concentrations of IL-6,IL-8,and TNF-αin group H were significantly lower than those in group B,and the concentration of IL-10 was significantly higher than that in group B（P<0.05）.In the remaining moments,there was no statistically significant difference in the comparison of IL-6,IL-8,IL-10,and TNF-αlevels between the two groups（P>0.05）.In the intra-group comparison,the differences were not statistically significant（P>0.05）when comparing IL-8 concentrations at T₆ and T₇ moments in both groups,IL-10 concentrations at T₇ and T₅ and T₆ moments in group B,and TNF-αconcentrations at T₅ and T₇ moments in group H.The differences were statistically significant（P<0.05）when comparing the remaining moments between the two groups.（3）Oxidative stress indexes:When comparing the MDA and SOD concentrations between the two groups,the differences were not statistically significant（P>0.05）.（4）Pulmonary function indexes:At the moments of T₄ and T₅,Cdyn was significantly higher in group H than in group B（P<0.05）,and the difference was not statistically significant when comparing the moments of T₂（P>0.05）.The differences were statistically significant when comparing different moments within the group（P<0.05）.When comparing A-a DO₂ and OI between the two groups,the differences were not statistically significant（P>0.05）.（5）Incidence of PPCs:When comparing the two groups,the difference was not statistically significant（P>0.05）..（6）Perioperative adverse reactions:the overall incidence of adverse reactions in patients in group H was significantly lower than that in group B（P<0.05）,among which the incidence of intraoperative hypotension and injection site pain in group H was significantly lower than that in group B（P<0.05）,and the differences were not statistically significant when the remaining adverse reactions were compared（P>0.05）.ConclusionIn patients undergoing thoracoscopic lobectomy:（1）Compared with propofol,ciprofol enhances intraoperative dynamic lung compliance,reduces postoperative inflammatory response,decreases the incidence of perioperative adverse events,and has a superior pulmonary protective effect;（2）However,the effects of both on intraoperative oxidative stress levels,pulmonary ventilation function,and the incidence of pulmonary complications in the first 7 days postoperatively are similar.