A Clinical Research About Pressor Response To Vasopressors In Prone Position Surgery Under General Anesthesia Combined With Dexmedetomidine

Objective Hypotension is a most common side effect of prone position during general anesthesia surgery.Ephedrine and phenylephrine（PE）are the commonly used vasopressors to restore blood pressure during surgery.Recently,Norepinephrine（NE）has been suggested as a potential alternative,its weakβ-adrenergic effects may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine.The use of norepinephrine to prevent and treat hypotension during prone position is new,and its use as a bolus has not been fully determined in this context。Different anesthesia state have an effect on patients responsing to vasopressors.Our previous study found that the body responded more strongly to ephedrine during general anesthesia than to spinal anesthesia.Addition of dexmedetomidine to general anesthesia may enhance the body’s response to intraoperative commonly used booster drugs.Compared with the supine position of general anesthesia,the body’s reaction to ephedrine and PE was enhanced in the supine position of general anesthesia.It has not been reported whether the reaction of the body to the commonly used booster drugs will be further enhanced by the use of dexmedetomine in the prone operation of general anesthesia.In order to compare the prone position surgery during general anesthesia,the body of the three kinds of commonly used drugs of pressure booster response,select the suitable for general anesthesia prone position surgery to correct intraoperative hypotension in the best drugs,we have designed this clinical study.The purpose of this study was to compare different vasopressor respondings to common vasoactive drugs,ephedrine,phenylephrine,and norepinephrine,when combining using DEX during prone position surgery under general anesthesia.At the same time we fosus on other hemodynamic variables and tissue perfusion.Methods In a randomized,double-blinded study,69 ASAI-II patients having posterior lumbar spinal infusion operation under general anesthesia were included.Excluding criteria were people youger than 18 years old,having serious kidney or liver diseases,allergy to any study medication,sinus bradycardia,serious atrioventricular block,peripheral vascular thrombosis,cerebrovascular disease,body mass index>35kg/m² or less than 18 kg/m².All patients had maintained absence from intake of solid substances as normally did before entering the operating room.Informed consent was obtained preoperatively from each patient.All surgery were performed during day time.After entering operation room,patients were bolus 5ml/kg colloid before anesthesia induction,then solution was maintained at a speed of 10ml/kg/h.Intraoperative infusion proportion crystal:colloid=2:1,combined with autologous blood transfusion.In this experiment,the equivalent dose of three drugs was given at ephedrine:PE:NE=1ug/kg:0.1mg/kg:0.06ug/kg.All three groups of patients were calculated to be given the same volumn of vasopressors,in the same form of 10ml syringe labelled with”study drug”to ensure intraoperative monitoring anesthesiologist blinded to study drug.After bolus DEX 0.4ug/kg for 10min,rapid sequential anesthesia induction was used.After intubation,patients were mechanically ventilized in a volumn-controlled mode,with fresh air 2L/min,oxygenation and air,FiO₂ 50%,I:E=1:2,volumn tidal 8ml/kg,PEEP 0cmH₂O,inspiration rates were adjusted to maintain PETCO₂ 40-45 mmHg。When having bolused DEX for 10min,infusion speed of DEX was adjusted to 0.2ug/kg/h during surgery.Anesthesia was maintained with1%-3%sevoflurance,remifentanil 5-10ug/kg/h..Before anesthesia induction,the electrode patch was attached to the patient’s frontal area to monitor the depth of anesthesia,and the intraoperative depth of anesthesia was monitored by Angel 6000A depth monitor.Sevoflurance was adjusted to maintain index of consciousness（IOC）40-60.About 30min after induction,when hemodynamic was stable,patients were turned prone position carefully.By the time MAP lower than 20%of baseline or SBP was 90-106mmHg,without surgery stimulation significantly changed and patients no arrhythmia and HR between45-100 beats per minute.Patients were randomized to receive an intravenous of ephedrine 0.1mg/kg（D/Egroup,n=22）,phenylephrine 1 ug/kg（D/Pgroup,n=23）or norepinephrine 0.06ug/kg（D/Ngroup,n=21）。During 10min study period,sevoflurance,remifentanil and fluid speeding was keeping stable and there was an independant assistant responsible for recording.Patients’cardiovascular variables recorded included heart rate（HR）and intra-arterial blood pressure.A Vigileo/Flotrac monitor system measured:cardiac output（CO）,stroke volume（SV）,systemic vascular resistence（SVR）,stroke volume variation（SVV）as well as central venous pressure（CVP）at baseline,time before and then every 1 minutes for 10 minutes after intravenous bolus vasopressors.Hemodynamic profiles over time in each treatment were compared.Arterial and central venous blood sample analysing were performed hourly during whole surgery,guaranting anesthesiologists would not be instructed by ScvO₂ or△PCO₂ values.Regional cerebral O₂ saturation（rSco₂）and parameters of tissue perfusion such as arterial lactate,central venous oxygen saturation（ScvO₂）,venous to arterial carbon dioxide gap（△PCO₂）were also recorded.Results 66 patients were included in final analysis.There was no significant difference in hemodynamic data between the baseline of supine position and the hemodynamic data beforeinfusion（P<0.05,P<0.05）.Anesthetic depths were sililar in three groups（P=0.125）.After bolus of vasopressor,intra-arterial blood pressure was elevated in all groups,of which ephedrine increased blood pressure higher and lasting longer than the others.The effectively lifting presure time compared with prevasopressors was 10min（T1-T10,P<0.005）in D/E group,8min（T1-T8,P<0.005）in D/P group,3min（T1-T3,P<0.005）in D/N group during observation period.SBP increased significantly with time in each group（P<0.001）.Compared with prevasopressor（T0）values,D/E group elevated SBP,diastolic blood pressure（DBP）,MAP respectively by 34.9%,30.1%,29.8%.MAP（P<0.001）was significantly improved for all three kinds of booster drugs compared with T0.The highest elevation MAP values of the three groups were 18.4 mmHg in group D/E,24.2 mmHg in group D/P and 15.2 mmHg in group D/N.Within 10min observation,MAP was 73.2mmHg in group D/E,66.6 mmHg in group D/P and 68.7 mmHg in group D/N.HR varies with time significantly（P<0.001）.Compared with T0,HR increased in group D/E（T1-T10,P<0.005）,with the fastest HR 58.1±10.1 beats/min.In D/P group,HR was slowed down（T1-T5,P<0.005）,and the slowest HR was 57.0±9.3 beats/min.There was no significant change in HR after injection in D/N group.Combined with vigileo/flotrac monitor system,intravenous injection of 0.1mg/kg ephedrine increased CO significantly（T1-T10,P<0.005）,and the maximum increase of CO was 25.5%,7.7%and 4.9%respectively during the observation period.There was no significant difference in the increase proportion of CO between groupD/P andgroup D/N（P=0.366）.Effective increase of SVR in D/P group lasted for 6min（P<0.005）,with maximum increase of SVR was 47.2%.SVwas relatively stable in D/N group（P=0.030）,and there was no significant difference in SV and CVP among three groups（P=0.535,P=0.260）.Both local hemodynamic changes and systemic metabolic perfusion were studied.The mean values of rSco₂ in the three groups before iv injection were 59.3±9.7%,58.5±10.3%,58.5±10.3%（P=0.989）.No significant change in rSco₂ was observed in three groups within 10min（P=0.089）.There was also no significant difference in perfusion parameters between groups.The mean values of ScvO₂ in three groups were 82.5±5.1%,82.1±5.5%,80.8±5.2%respectively（P=0.723）,and the lowest values of S_CVO₂min in three groups was79.2±5.8%.Intraoperative lactic acid was all in normal range.Conclusion Combination of dexmedetomidine in prone position can potentiate the pressor response to vasopressors in terms of magnitude and lasting time.Accompanying incresing CO,pressor response to intravenous ephedrine in patients under posterior lumbar spinal infusion operation was augmented,higher than that of phenylephrine and norepinephrine.Saturation of regional cerebral tissue oxygenation was higher than cerebral ischemia limit and had no significant change during the experient.Arteriovenous blood gas monitoring(S_CVO₂,Lac,△PCO₂)showed no systemic perfusion deficiency.