Effects Of Penehyclidine Hydrochloride Combined With Dexmedetomidine On Pulmonary And Brain Function In Patients Undergoing Heart Valve Surgery

Objective To investigate the effects of penehyclidine hydrochloride combined with dexmedetomidine on lung function and brain function in patients undergoing heart valve surgery under cardiopulmonary bypass.Methods A prospective randomized controlled study was performed.180patients undergoing cardiopulmonary bypass（CPB）heart valve surgery were divided into four groups:penehyclidine hydrochloride group（group P）,dexmedetomidine group（group D）,penehyclidine hydrochloride combined with dexmedetomidine group（group PD）and normal saline group（group C）.In group P,penehyclidine hydrochloride was injected intravenously 10 minutes before anesthesia induction and immediately after cardiopulmonary bypass begins,with a total amount of 0.04 mg/kg;In group D,after anesthesia induction,dexmedetomidine was continuously injected at the rate of 0.5μg/kg/h until the end of anesthesia;PD group was injected with penehyclidine hydrochloride 0.02 mg/kg intravenously 10 minutes before anesthesia induction and immediately after cardiopulmonary bypass begins,with a total amount of0.04 mg/kg,and after anesthesia induction,dexmedetomidine was continuously injected at the rate of 0.5μg/kg/h until the end of anesthesia;In group C,the same dose of normal saline was injected intravenously or continuously pumped at the corresponding time points.All patients received the same anesthesia and perioperative management protocol.Radial artery blood and internal jugular vein bulb blood were collected before anesthesia induction（T0）,before skin incision（T1）,before CPB（T2）,30 min after starting CPB（T3）,30 min（T4）,6 h（T5）,24 h（T6）after CPB-cessation.Blood gas analysis was performed,and variates such as alveolar-arterial oxygen partial pressure（A-a DO₂）,oxygenation index（OI）,respiratory index（RI）,arterio-jugular bulb venous oxygen content difference（Ca-jv O₂）and cerebral extraction rate of oxygen（CERO₂）were calculated.At the same time,r Sc O₂ was monitored and the concentrations of plasma TNF-α,IL-6,CRP,PCT,S-100βand NSE in venous blood were measured.The incidence of postoperative pulmonary complications,postoperative delirium and postoperative cognitive dysfunction was evaluated.The postoperative recovery time,time to extubation,ICU stay,postoperative hospital stay and adverse events were recorded.Results（1）There was no significant difference in the basic physical conditions and preoperative general assessment among the four groups（P>0.05）.（2）Compared with group C,OI increased and RI decreased in groups P,D,and PD after cardiopulmonary bypass;Compared with groups P and D,OI increased and RI decreased significantly in the PD group（P<0.05）.（3）Compared with group C,Sjv O₂ increased and Ca-jv O₂,CERO₂ decreased in groups P,D,and PD after cardiopulmonary bypass（P<0.05）,and the r Sc O₂effectively increased in the PD group（P<0.05）.Compared with groups P and D,Sjv O₂ increased and Ca-jv O₂ decreased significantly in the PD group（P<0.05）.（4）Compared with group C,the levels of plasma inflammatory factors TNF-α,IL-6,CRP and PCT decreased after cardiopulmonary bypass（P<0.05）;Compared with groups P and D,the levels of TNF-αand IL-6 in the PD group decreased significantly（P<0.05）.（5）Compared with group C,the levels of plasma brain injury biomarker S-100βand NSE after cardiopulmonary bypass decreased in groups P,D and PD（P<0.05）;Compared with groups P and D,the levels of S-100βand NSE decreased obviously in the PD group（P<0.05）.（6）Compared with group C,the score of pulmonary complications after cardiopulmonary bypass decreased in groups P,D and PD（P<0.05）,the incidence of postoperative pulmonary complications was effectively reduced in the PD group（P<0.05）,and the extubation time and ICU stay time were shortened in the PD group（P<0.05）.（7）There was no significant difference in the incidence of postoperative delirium,postoperative cognitive dysfunction and adverse events among the four groups（P>0.05）.Conclusions 1.Penehyclidine hydrochloride or dexmedetomidine used in patients undergoing cardiopulmonary bypass heart valve surgery can inhibit the release of inflammatory factors,increase oxygenation index,decrease respiratory index and postoperative pulmonary tension score;And the combined effect of the two drugs is stronger than that of a single drug in reducing the release of TNF-αand IL-6,increasing oxygenation index and reducing respiratory index.It can also effectively reduce the incidence of postoperative pulmonary complications and shorten the extubation time and ICU stay time.2.Penehyclidine hydrochloride or dexmedetomidine can inhibit the release of inflammatory factors and brain injury biomarker S-100βand NSE,increase Sjv O₂ and decrease Ca-jv O₂ and CERO₂;And the combined effect of the two drugs is stronger than that of a single drug in reducing the release of TNF-α,IL-6,S-100βand NSE,increasing Sjv O₂ and decreasing Ca-jv O₂.The combined effect of the two can also increase r Sc O₂,improve cerebral perfusion and cerebral oxygen content,and not increase the incidence of postoperative adverse events.But they do not affect neuropsychiatric symptoms.