急性过度通气对颅内高压犬脑功能的影响
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摘要
机械通气在医疗实践中发挥越来越大的作用,其涉及到临床麻醉、重症监测治疗和复苏。早在1832年Dalziel就成功研制成第一台负压呼吸机;1928年Driker-Shaw成功研制成的“铁肺”(iron lung),从而开创了机械通气的新纪元。此后近一个世纪里,机械通气成功地解救了无数患者生命。同时,过度通气所致呼吸性碱中毒作为机械通气的一个并发症,对机体产生的重要影响也日益受到人们的重视。
过度通气是指通气超过生理所需而引起的一组症候群,若血浆H_2CO_3原发性减少低于正常值下限(PaCO2＜35mmHg)且PH＞7.45则称为呼吸性碱中毒。呼吸性碱中毒在24h内发生者则称为急性呼吸性碱中毒。多年来,医学界对呼吸性酸中毒的研究报导较多,而关于呼吸性碱中毒的报道却很少,因为呼吸性碱中毒多见于机械控制通气和癔病综合征。临床上过度通气常常用于全麻诱导、气管拔管、腹腔镜手术和外伤所致的颅内高压等。尤其在外伤性颅内高压中,常采用过度通气降低颅内压。过度通气降低颅内压是利用CO_2化学调节作用,低CO_2可使脑血管收缩,减少脑灌注,从而降低颅内压,为手术创造相对清晰的视野。
Morno-Kellie原理认为由脑组织、脑血容量、脑脊液三者组成的颅腔内容物中,产生调节作用的只有依赖脑血流量和脑脊液。但是过度通气导致的脑血管收缩却使原本处于缺血水平的脑细胞供血进一步减少。已有大量研究证实,过度通气不仅仅涉及到大脑的血供问题,而且有着广泛的生理效应,如引起低钾血症,酸碱平衡失调等。目前医学界认同重度过度通气引起的脑缺血,但对于过度通气是如何导致脑循环障碍及临床实践中过度通气的时程仍缺乏一致性,另外过度通气对于脑外伤颅内高压患者所致重要电解质的变化规律知之甚少,因此本课题带着这样的疑问,建立犬急性硬膜外血肿颅内高压模型,就相关问题进一步深入研究。
方法
一、资料及分组
健康雄性家犬25只,年龄为2～4岁,体重13～15.5kg,常规饲养一周。禁食10h,禁饮6h。随机分为5组(A、B、C、D和E组,每组5只),采用硬膜外球囊膨胀法建立犬急性颅内高压模型,各组先机械通气30min,维持P_(ET)CO_2在32-45mmHg之间:其中A组仅放置硬膜外球囊和颅内压力传感器,不膨胀球囊。
二、麻醉和建立监测
犬腹腔注射3%戊巴比妥钠30mg/Kg麻醉,气管插管,在保留自主呼吸下颈内静脉逆行穿刺连接三通管用于监测CVP、输液及采血。股动脉穿刺连接压力传感器连续测量MAP和采血,连接多参数监护仪,连续检测肛温、P_(ET)CO_2、HR、ECG、iBP和SPO_2等指标。
三、犬颅内高压模型建立
犬俯卧位,双外耳道连线距中线1cm处分别钻孔。左顶钝头细套管针脑室穿刺深约6mm接压力传感器。右顶硬膜外置乳胶球囊。术中充分止血,骨蜡密封骨孔。匀速向球囊内注入37℃生理盐水3～5ml,60sec内颅内压升至60±3mmHg后停止注射。判定颅内高压标准为:犬一侧瞳孔扩大、呼吸变缓及CT显示硬膜外占位。
四、监测指标
颅内高压3h后,维库溴铵0.8mg/kg静脉注射打断犬自主呼吸,连接呼吸机通气。A组家犬为空白对照组,硬膜外球囊内不注射液体,仅机械通气维持P_(ET)CO_2在32-45mmHg。B(正常通气组)、C(轻度通气组)和D(中度通气组)和E组(重度通气)建立硬膜外血肿颅内高压模型,机械通气30min后(P_(ET)CO_2范围在32-45mmHg)。调节呼吸机参数,B、C、D、E组P_(ET)CO_2分别维持在32-45、25-32、25-20及20mmHg以下持续通气60min。各组在术前及所设P_(ET)CO_2数值段内每10min采集颈静脉和股动脉血各0.5ml血气分析。另外测动静脉血血糖(BS)和乳酸(Lac)。在硬膜外球囊膨胀前(T_1)、过度通气后2h(T_2)、6h(T_3)、12h(T_4)、24h(T_5)和48h(T_6)各采集颈静脉血4mL,应用酶联免疫吸附法测定S100B和CRP含量。过度通气结束后排空球囊液体,此后2h(P_2)、6h(P_6)和12h(P_(12))分别进行神经功能缺损评分。48h后处死,取犬不同部位脑组织病理分析。
五、犬脑血流动力学检测
经颅多普勒超声仪(TCD),探头置于球囊同侧颞窗,调整探头获得最佳大脑中动脉(CMA)血流信号,记录收缩期峰值血流速度(Vs)、舒张期末血流速度(Vd)、平均血流速度(Vm)、搏动指数(PI)和阻力指数(RI)。同时计算脑氧利用率(O_2Ucc)、动静脉氧含量差(A-VDO_2)、脑氧耗量(CRO_2)、动静脉乳酸含量差(Da-juL)、脑氧摄取率(ERO_2)、脑氧耗量(Da-jvO_2)和动静脉糖含量差(Da-juglu)。
结果
除A组外,余20条家犬均成功建立急性硬膜外血肿颅内高压模型,按照预定时间完成过度通气。球囊膨胀时犬心率减慢、血压升高、呼吸减慢、单侧瞳孔扩大,与膨胀前比较有显著性差异(P＜0.05)。
一、随着过度通气的进行,动脉血中K~+、Ca~(2+)、PaCO_2和HCO_3~-进行性降低,pH逐渐升高,PaCO_2下降与K~+呈现正相关,相关系数r=0.9196(P＜0.01)。PaCO_2与血钙的相关系数为0.1973(P＜0.05),CL~-和Na~+基本保持不变。各组过度通气前后SaO_2维持不变(P＞0.05)。颈内静脉血气在中度过度通气后PH进行下降,严重过度通气则降到低点达到7.11±0.04(P＜0.05)。球囊扩张后,轻中度过度通气SjvO_2不变,D组和E组SjvO_2降至最低达到(42±6)%。
二、与A组相比,球囊扩张后,动脉和静脉血中BS及Lac急剧升高,以静脉增加明显,动静脉BS浓度差增加(P＜0.05),轻度过度通气Lac轻微降低,重度过度通气则使二者浓度更加升高(P＜0.05),重度过度通气组脑动静脉Lac含量差(Da-juL)增加,与A组比较差异显著(P＜0.05)。
三、球囊扩张后,犬心率减慢,血压和颅内压急剧升高,颅内压由术前的13±3.4 mmHg增加到60±3.0mmHg,与术前比较有显著性差异(P＜0.05)。当P_(ET)CO_2在25-35mmHg范围测得的PaCO_2与ICP呈现高度正相关r=0.9958,P＜0.01。轻度过度通气使颅内压轻微降低,但仍然高于术前。重度过度通气(P_(ET)CO_2＜20mmHg)时颅内压改变不大。
四、脑氧供需:球囊扩张后,SjvO_2逐渐降低,过度通气P_(ET)CO_2的下降伴随SjVO_2也下降,当P_(ET)CO_2＜20mmHg时降到最低点。Da-jvO_2随着过度通气加深而降低,但当中度过度通气时Da-jvO_2则增加明显,与手术前和球囊扩张后比较有显著性差异(P＜0.05)。轻度过度通气时氧摄取率改变不大,但重度过度通气使氧摄取率明显降低,与术前比较有显著性差异(P＜0.05)。
五、经颅多谱勒超声监测:硬膜外球囊扩张后大脑中动脉出现Vs和Vd显著减慢,PI和RI增大,与创伤前相比有显著性差异(P＜0.05)。轻度过度通气时,Vs有一定回升,但仍然处于低水平。当P_(ET)CO_2＜25mmHg时,Vs、Vd值达到最低,随过度通气的加深其值改变不大。
六、S100B和CRP含量变化:所有犬硬膜外球囊扩张后S100B和CRP的含量不同程度升高(P＜0.05)。各组S100B蛋白6h后开始升高,12h达到峰值(2.08±0.32μg/L),24h轻微下降,D组升高尤明显,与术前比较差异显著(P＜0.05);CRP在实验组中2h后迅速增高,6h达到峰值(21.8±2.5mg/L)一直持续到48h,与球囊扩张前比较差异显著(P＜0.05),D组CRP增加更高,6h达到29.4±5.7mg/L,与其余各组比较有显著性差异(P＜0.05)。
七、神经功能评分:所有犬在过度通气后2h内神经功能评分较高,6h段分值降低,且随时间延长分值降低。重度过度通气组在手术后2h和6h的分值较高,与其余各组比较有显著性差异(P＜0.05)。而在12h后则与其它各组比较无显著性差异(P＞0.05)。在同一时间点A组、B组、C组和E组的神经功能评分并无显著性差异(P＞0.05)。
八、病理分析:实验组球囊受压处脑组织软化、肿胀、色泽变暗,对侧脑组织结构基本正常。高倍光镜下皮质受压处大量脑细胞坏死,坏死带向脑组织深部延伸逐渐减轻,并伴脑实质部压迫性出血。周围皮质脑细胞坏死散在分布,脑细胞肿胀。D组较其它各组坏死细胞分布更广泛,脑组织肿胀明显。电镜下见坏死脑细胞结构模糊,脑细胞内线粒体空泡化以及溶解改变。
结论
一、急性过度通气影响体电解质、酸碱的变化,使动脉血中PH值升高、K~+、Ca~(2+)降低。PaCO_2每降低10mmHg,K~+降低0.5mmol/L,Ca~(2+)降低0.05mmol/L。
二、当P_(ET)CO_2在25-35mmHg范围时,PaCO_2与ICP呈正相关关系,大于该范围,则颅内压降低不显著;小于该范围,会导致脑血液供应减少。严重通气引起脑氧供需失衡。
三、急性过度通气影响血流动力学的变化,轻中度过度通气利于改善颅内高压引起的高血压作用。
四、S100B和CRP浓度变化能够反映大脑受损的程度,其变化与神经功能受损评分具有一致性。
五、重度过度通气对硬膜外血肿犬引起脑缺血可能因为脑血管过度收缩,脑细胞利用氧障碍、氧供需失衡等诸多因素综合作用的结果。
六、重度过度通气延迟颅内高压犬麻醉苏醒时间。
Mechanical ventilation plays an important role in medical practice,which involves in clinical anesthesia,ICU and resuscitation.Mechanical ventilation experenced a long time.In 1832,Dalziel developed a negative pressure breathing machine;In 1928, Driker-Shaw developed"iron lung".From then on,a new epoch of mechanical ventilation developed.Within about one century,mechanical ventilation successfully saved a lot of patients'lives.At the same time,more and more doctors thought highly of hyperventilation,but,a new problem occurred,a complication of mechanical ventilation, could produce some important effects on organisms.
Hyperventilation means a series of syndrome that ventilation produces once its role surpasses physiological need.When H_2CO_3 level of blood plasma decreased lower limit of normal(PaCO_2＜35mmHg) and PH＞7.45,as called respiratory alkalosis.Acute respiratory alkalosis means respiratory alkalosis takes place within 24 hours.About one century,medical scholars placed much energy to respiratory acidosis,but they paid little attention to respiratory alkalosis because respiratory alkalosis often existed mechanical ventilation and Hysteria Syndrome.At present clinical practice,hyperventilation is frequently used in induction of general anesthesia,extubation,laparoscopic operation,acute intracranial hypertension of trauma and so on,Especially in the traumatic intracranial hypertension.Hyperventilation is often used to reduce intracranial hypertension.Its role of lowering ICP depends on CO_2 chemical regulation in CNS.low CO_2 in blood makes Cerebral vessels constrict,which can reduce cerebral perfusion and ICP,thus,hyperventilation is frequently used to reduce bleeding during operation.
Morno-Kellie's principle points out that cranium content consists of brain tissue, cerebral blood volume and cerebrospinal fluid(CSF).Only both cerebral blood volume and CSF is spontaneously regulatable.The alteration of cranium content pressure mainly depends on cerebral blood volume and CSF.But,severe cerebral vasoconstriction does much harm to brain cells.Meanwhile,many studies demonstrated that hyperventilation not only induced cerebral ischemia but also brought wide physiological role such as kaliopenia,acid-base disturbance,etc.Even though many doctors agree on the fact that severe hyperventilation can produce cerbral ischemia,few doctors know how circulatory disorder of brain takes place and how suitable time of hyperventilation is.In addition,they really don't know how electrolytics alter when given hyperventilation.So we establish the intracranial hypertension model of extradural hematoma to make deep study on these problems.
Methods
25 healthy male dogs,received retro-grade jugular bulb venous catheterization and arterial catheterization,were randomly divided into 5 groups;A,B,C,D and E group(each=5).Dogs but A group were hyperventilated after epidural balloon inflation set up and built up animal model of introcranial hypertention by injecting 3-5ml 0.9%NS into lactoprene balloon of epidura.Dogs'P_(ET)CO_2 in B,C,D and E group will be maintained 32-45,25-32,25-20 and below 20 mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular jugular blood and femoral artery blood was taken suction respectively at different P_(ET)CO_2 period for measuring blood gas,VO_2,DO_2,ERO_2,lactic acid and blood sugar every 10 min when dogs'P_(ET)CO_2 chalks numerical value Booked.Vs,Vd,Vm,Pi and RI in MCA will be recorded by using Transcranial Doppler(TCD).Meanwhile,cerebral oxygen delivery/supply will be calculated according to blood gas analysis results.
1、Data and Grouping
25 Healthy male dogs,age from 2 to 4 years,body weight from 13 to 15.5Kg,will raise for one week,fasting for 12hrs,no drinking for 6hs.before experiment,are randomly divided into 5 groups(A、B、C、D and group E,each=5).Dogs in group A were placed a sacculus into epidural cavity but no inflatiing.The sacculus of dogs in any other groups was all inflated as the model of acute intracranial hypertension.All dogs were given 30min normal ventilation and P_(ET)CO_2 kept 32-45mmHg.
2、Anesthetizing and Monitoring
sodium pentobarbital according to 30mg/Kg was injected into abdominal cavity for anesthetizing dogs,and afterward intubation was operated.Internal jugular vein punctured under spontaneously breathing for monitoring CVP,infusing fluit and collecting blood.Femoral artery punctured for monitoring blood pressure and collecting blood.Multiparameter monitors continuosly detected body temperature, P_(ET)CO_2,HR,ECG,iBP and SPO_2.
3、Establishing dog's model of intracranial hypertension
Establish dog's model of intracranial hypertension by adopting epidural sacculus inflation.Place dogs to prone position,ambi-outer ear line 1cm distance between median line was drilled respectively.A trochar in left brain would be intubated to side ventricula to monitor ICP,and a foam rubber sacculus was placed into epidural cavity. Then,3～5ml 37℃physiological saline was injected into the sacculus within 60 seconds and kept ICP 60±3mmHg range.The symptoms of acute intracranial hypertension were as follows:side corediastasis,breathing alleviated or CT Image of occupyed Epidural.
4、Targets monitored
After kept acute intracranial hypertension for 3hs,0.8mg/kg vecuronium bromide I.v.then given mechanical ventilation.The dogs of group A,control group,without inflation.P_(ET)CO_2 in group A will be kept from 32 to 45mmHg under ventilatiing.Group B(normal breathing),group C(mild hyperventilation),group D(midrange hyperventilation) and group E(severe hyperventilation)set up the model of intracranial hypertension.After kept P_(ET)CO_2 normal level for 30min,P_(ET)CO_2 of B,C,D and group E would be kept 32-45,25-32,25-20 and below 20mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular blood and femoral artery blood was taken suction respectively every 10min in different P_(ET)CO_2 period for measuring blood gas,blood lactic acid and blood sugar.Meanwhile,4mL jugular blood will be collected in pre-inflation(T_1),post hyperventilation 2h(T_2),6h(T_3),12h(T_4) 24h(T_5) and 48h(T_6) for measuring content of S100B and CRP.drawn out hydatid fluid from balloon after hyperventilation.Neurological deficits scoring was evaluated at post hyperventilation 2h,6h and 12h.dogs would be put to death for pathological analysis at 48h.
5、Monitoring CBF
put detecting head of TCD to temple and adjust detecting head untill getting best signal of CMA.Vs、Vd、Vm、Pi and RI in MCA were recorded by using Transcranial Doppler in differently time.meanwhile O_2Ucc,A-VDO_2,Da-juL,ERO_2,Da-jvO_2 and Da-juglu will be calculated by blood gas value.
Results
Except group A,other any dogs were all established the model of intracranial hypertension and finished this experiment sucessfully.when sacculus inflated,Heart rate got slow,blood pressure increased,respirary frequency reduced and side pupil dilatated (P＜0.05) when compared with pre-inflation.
1、Blood gas analysis
With the hyperventilation development,K~+,Ca~(2+),PaCO_2 and HCO_3~-in arterial Blood decreased gradually.PH increased gradually,there existed a positive correlation between PaCO_2 and K~+.its coefficient correlation r=0.9196(P＜0.01).Coefficient correlation between PaCO_2 and Ca~(2+) r=0.9196(P＜0.01).CL~-,SaO_2 and Na~+ kept changeless(P＞0.05).PH decreased with hyperventlation,and got the lowest point 7.11±0.04(P＜0.05) when given severe hyperventilation.SjvO_2 in mild and midrange hyperventilation group kept changeless.But SjvO_2 in group D and group E got lowest point(42±6)%.
2、Blood Sugar and Lactic Acid
When compared with group A,Blood Sugar and Lactic Acid in experimental groups increased rapidly after inflation especially BS and Lac of jugular blood. Da-juglu increased(P＜0.05),Lactic acid in group mild hyperventilation decreased slightly,but severe hyperventilation makes BS and Lac increase(P＜0.05).Da-juL in group D increased sharply,there is significant difference between group A and group D (P＜0.05).
3、ICP and Hemodynamics
After balloon inflated,all dogs'HR decreased quickly,blood pressure and ICP increased.ICP increased from 13±3.4 mmHg in pre-operative to 60±3.0mmHg,there is significant difference when compared with pre-operation(P＜0.05).when value of P_(ET)CO_2 kept from 25 to 35mmHg,it revealed a positive coefficient correlation of PaCO_2 and ICP r=0.9958(P＜0.01).mild hyperventilation can reduce ICP slightly but its value is much higher than pre-opration.With severe hyperventilation development (P_(ET)CO_2＜20mmHg),ICP still kept changeless.
4、DO_2 and VO_2
When inflated,SjvO_2 dcreased quickly with P_(ET)CO_2.when P_(ET)CO_2＜20mmHg, SjvO_2 reached the lowest point.Da-jvO_2 decreased gradually with hyperventilation.but Da-jvO_2 in midrange hyperventilation increased significantly when compared with pre-operation or post-inflation(P＜0.05).ERO_2 in mild hyperventilation group changed slightly,but severe hyperventilation made ERO_2 decrease significantly when compared with pre-operation(P＜0.05).
5、Transcranial Doppler sonography(TCD)
After inflation,TCD showed Vs and Vd got slow greatly after epidural balloon expanded(P＜0.05).PI and RI increased significantly when compared with pre-trauma(P＜0.05).Athough Vs increased in mild hyperventilation,the value of PI and RI in B,C,D and E group grew higher than A group(P＜0.05).when P_(ET)CO_2＜25mmHg,Vs and Vd got its slowest point and showed much significant difference(P< 0.05) with P_(ET)CO_2 lowering.When P_(ET)CO_2＜25mmHg,Vs and Vd got its lowest point and kept changeless when hyperventilation deepened.
6、S100B and CRP
When inflated,S100B and CRP in experimental group increased at different degree (P＜0.05).S100B started to grow in 6h,peaked in 12h(2.08±0.32μg/L),decreased slightly in 24h.The value of S100 in group D grew more than pre-operation and other any groups(P＜0.05).CRP grew rapidly in 2h,peaked in 6h(21.8±2.5mg/L) untill 48h, there was significant difference when compared with pre-inflation(P＜0.05).CRP in group D grew most quickly of all groups,its value reached 29.4±5.7mg/L in T_5(P＜0.05).
7、Neurological Deficits Scoring(NDS)
After 2h hyperventilation,Neurological Deficits Scoring of all dogs was much high.their score decreased from time to time.NDS in severe hyperventilation group was higher in 2h and 6h than any other groups(P＜0.05 )but no significant difference in 12h(P＞0.05).There was no significant difference between group A,B and C at the sametime(P＞0.05).
8、Pathological analysis
Dogs's brain tissue of area compressed in experimental groups sofetened,swollen and blackened but other side brain tissue kept normal.Under light microscope,brain tissue in compressed area got necrosed mostly.and necrosis band extended to deep brain tissue and got lessened gradually in deep brain area.Necrosis cells in brain of group D diffused distribution.Necrosis was more wider than any other groups.Under electronical microscope,we can see the structure of the necrosis cells get blurred.Mitochondrium vacuolizated and dissolved.
Conclusions
1、Acute hyperventilation have much important effect on electrolytics and acid base,and it makes PH increase,K~+ and Ca~(2+) decrease.Blood K~+ reduced 0.5mmol/L and Blood Ca~(2+) reduced 0.05mmol/L when PaCO_2 reduced every 10mmHg.
2、When P_(ET)CO_2 kept from 25 to 35mmHg,ICP decreased with PaCO_2.when PaCO_2 exceed 35mmHg,ICP dcreased slightly;when PaCO_2 was reduced to 25 mmHg,cerebral ischemia could take place.Severe hyperventilation results in Disequilibrium of O_2 Supply/Need.
3、Acute hyperventilation have an important effect on hemodynamics of organism.mild and midrange hyperventilation alleviated hypertension brought about by acute intracranial hypertension.
4、Density of S100Band CRP shows the extent and level of injuried brain,their change have coincidence with NDS.
5、Severe hyperventilation resulted in cerebral ischemia lies in Cerebral vessels constricted exceptionally,and obstacle of brain's oxygen intaking plays an important role in cerbral ischemia also.
6、Severe hyperventilation delayed palinessthesia time of dogs with acute intracranial hypertension.
过度通气是指通气超过生理所需而引起的一组症候群,若血浆H_2CO_3原发性减少低于正常值下限(PaCO2＜35mmHg)且PH＞7.45则称为呼吸性碱中毒。呼吸性碱中毒在24h内发生者则称为急性呼吸性碱中毒。多年来,医学界对呼吸性酸中毒的研究报导较多,而关于呼吸性碱中毒的报道却很少,因为呼吸性碱中毒多见于机械控制通气和癔病综合征。临床上过度通气常常用于全麻诱导、气管拔管、腹腔镜手术和外伤所致的颅内高压等。尤其在外伤性颅内高压中,常采用过度通气降低颅内压。过度通气降低颅内压是利用CO_2化学调节作用,低CO_2可使脑血管收缩,减少脑灌注,从而降低颅内压,为手术创造相对清晰的视野。
Morno-Kellie原理认为由脑组织、脑血容量、脑脊液三者组成的颅腔内容物中,产生调节作用的只有依赖脑血流量和脑脊液。但是过度通气导致的脑血管收缩却使原本处于缺血水平的脑细胞供血进一步减少。已有大量研究证实,过度通气不仅仅涉及到大脑的血供问题,而且有着广泛的生理效应,如引起低钾血症,酸碱平衡失调等。目前医学界认同重度过度通气引起的脑缺血,但对于过度通气是如何导致脑循环障碍及临床实践中过度通气的时程仍缺乏一致性,另外过度通气对于脑外伤颅内高压患者所致重要电解质的变化规律知之甚少,因此本课题带着这样的疑问,建立犬急性硬膜外血肿颅内高压模型,就相关问题进一步深入研究。
方法
一、资料及分组
健康雄性家犬25只,年龄为2～4岁,体重13～15.5kg,常规饲养一周。禁食10h,禁饮6h。随机分为5组(A、B、C、D和E组,每组5只),采用硬膜外球囊膨胀法建立犬急性颅内高压模型,各组先机械通气30min,维持P_(ET)CO_2在32-45mmHg之间:其中A组仅放置硬膜外球囊和颅内压力传感器,不膨胀球囊。
二、麻醉和建立监测
犬腹腔注射3%戊巴比妥钠30mg/Kg麻醉,气管插管,在保留自主呼吸下颈内静脉逆行穿刺连接三通管用于监测CVP、输液及采血。股动脉穿刺连接压力传感器连续测量MAP和采血,连接多参数监护仪,连续检测肛温、P_(ET)CO_2、HR、ECG、iBP和SPO_2等指标。
三、犬颅内高压模型建立
犬俯卧位,双外耳道连线距中线1cm处分别钻孔。左顶钝头细套管针脑室穿刺深约6mm接压力传感器。右顶硬膜外置乳胶球囊。术中充分止血,骨蜡密封骨孔。匀速向球囊内注入37℃生理盐水3～5ml,60sec内颅内压升至60±3mmHg后停止注射。判定颅内高压标准为:犬一侧瞳孔扩大、呼吸变缓及CT显示硬膜外占位。
四、监测指标
颅内高压3h后,维库溴铵0.8mg/kg静脉注射打断犬自主呼吸,连接呼吸机通气。A组家犬为空白对照组,硬膜外球囊内不注射液体,仅机械通气维持P_(ET)CO_2在32-45mmHg。B(正常通气组)、C(轻度通气组)和D(中度通气组)和E组(重度通气)建立硬膜外血肿颅内高压模型,机械通气30min后(P_(ET)CO_2范围在32-45mmHg)。调节呼吸机参数,B、C、D、E组P_(ET)CO_2分别维持在32-45、25-32、25-20及20mmHg以下持续通气60min。各组在术前及所设P_(ET)CO_2数值段内每10min采集颈静脉和股动脉血各0.5ml血气分析。另外测动静脉血血糖(BS)和乳酸(Lac)。在硬膜外球囊膨胀前(T_1)、过度通气后2h(T_2)、6h(T_3)、12h(T_4)、24h(T_5)和48h(T_6)各采集颈静脉血4mL,应用酶联免疫吸附法测定S100B和CRP含量。过度通气结束后排空球囊液体,此后2h(P_2)、6h(P_6)和12h(P_(12))分别进行神经功能缺损评分。48h后处死,取犬不同部位脑组织病理分析。
五、犬脑血流动力学检测
经颅多普勒超声仪(TCD),探头置于球囊同侧颞窗,调整探头获得最佳大脑中动脉(CMA)血流信号,记录收缩期峰值血流速度(Vs)、舒张期末血流速度(Vd)、平均血流速度(Vm)、搏动指数(PI)和阻力指数(RI)。同时计算脑氧利用率(O_2Ucc)、动静脉氧含量差(A-VDO_2)、脑氧耗量(CRO_2)、动静脉乳酸含量差(Da-juL)、脑氧摄取率(ERO_2)、脑氧耗量(Da-jvO_2)和动静脉糖含量差(Da-juglu)。
结果
除A组外,余20条家犬均成功建立急性硬膜外血肿颅内高压模型,按照预定时间完成过度通气。球囊膨胀时犬心率减慢、血压升高、呼吸减慢、单侧瞳孔扩大,与膨胀前比较有显著性差异(P＜0.05)。
一、随着过度通气的进行,动脉血中K~+、Ca~(2+)、PaCO_2和HCO_3~-进行性降低,pH逐渐升高,PaCO_2下降与K~+呈现正相关,相关系数r=0.9196(P＜0.01)。PaCO_2与血钙的相关系数为0.1973(P＜0.05),CL~-和Na~+基本保持不变。各组过度通气前后SaO_2维持不变(P＞0.05)。颈内静脉血气在中度过度通气后PH进行下降,严重过度通气则降到低点达到7.11±0.04(P＜0.05)。球囊扩张后,轻中度过度通气SjvO_2不变,D组和E组SjvO_2降至最低达到(42±6)%。
二、与A组相比,球囊扩张后,动脉和静脉血中BS及Lac急剧升高,以静脉增加明显,动静脉BS浓度差增加(P＜0.05),轻度过度通气Lac轻微降低,重度过度通气则使二者浓度更加升高(P＜0.05),重度过度通气组脑动静脉Lac含量差(Da-juL)增加,与A组比较差异显著(P＜0.05)。
三、球囊扩张后,犬心率减慢,血压和颅内压急剧升高,颅内压由术前的13±3.4 mmHg增加到60±3.0mmHg,与术前比较有显著性差异(P＜0.05)。当P_(ET)CO_2在25-35mmHg范围测得的PaCO_2与ICP呈现高度正相关r=0.9958,P＜0.01。轻度过度通气使颅内压轻微降低,但仍然高于术前。重度过度通气(P_(ET)CO_2＜20mmHg)时颅内压改变不大。
四、脑氧供需:球囊扩张后,SjvO_2逐渐降低,过度通气P_(ET)CO_2的下降伴随SjVO_2也下降,当P_(ET)CO_2＜20mmHg时降到最低点。Da-jvO_2随着过度通气加深而降低,但当中度过度通气时Da-jvO_2则增加明显,与手术前和球囊扩张后比较有显著性差异(P＜0.05)。轻度过度通气时氧摄取率改变不大,但重度过度通气使氧摄取率明显降低,与术前比较有显著性差异(P＜0.05)。
五、经颅多谱勒超声监测:硬膜外球囊扩张后大脑中动脉出现Vs和Vd显著减慢,PI和RI增大,与创伤前相比有显著性差异(P＜0.05)。轻度过度通气时,Vs有一定回升,但仍然处于低水平。当P_(ET)CO_2＜25mmHg时,Vs、Vd值达到最低,随过度通气的加深其值改变不大。
六、S100B和CRP含量变化:所有犬硬膜外球囊扩张后S100B和CRP的含量不同程度升高(P＜0.05)。各组S100B蛋白6h后开始升高,12h达到峰值(2.08±0.32μg/L),24h轻微下降,D组升高尤明显,与术前比较差异显著(P＜0.05);CRP在实验组中2h后迅速增高,6h达到峰值(21.8±2.5mg/L)一直持续到48h,与球囊扩张前比较差异显著(P＜0.05),D组CRP增加更高,6h达到29.4±5.7mg/L,与其余各组比较有显著性差异(P＜0.05)。
七、神经功能评分:所有犬在过度通气后2h内神经功能评分较高,6h段分值降低,且随时间延长分值降低。重度过度通气组在手术后2h和6h的分值较高,与其余各组比较有显著性差异(P＜0.05)。而在12h后则与其它各组比较无显著性差异(P＞0.05)。在同一时间点A组、B组、C组和E组的神经功能评分并无显著性差异(P＞0.05)。
八、病理分析:实验组球囊受压处脑组织软化、肿胀、色泽变暗,对侧脑组织结构基本正常。高倍光镜下皮质受压处大量脑细胞坏死,坏死带向脑组织深部延伸逐渐减轻,并伴脑实质部压迫性出血。周围皮质脑细胞坏死散在分布,脑细胞肿胀。D组较其它各组坏死细胞分布更广泛,脑组织肿胀明显。电镜下见坏死脑细胞结构模糊,脑细胞内线粒体空泡化以及溶解改变。
结论
一、急性过度通气影响体电解质、酸碱的变化,使动脉血中PH值升高、K~+、Ca~(2+)降低。PaCO_2每降低10mmHg,K~+降低0.5mmol/L,Ca~(2+)降低0.05mmol/L。
二、当P_(ET)CO_2在25-35mmHg范围时,PaCO_2与ICP呈正相关关系,大于该范围,则颅内压降低不显著;小于该范围,会导致脑血液供应减少。严重通气引起脑氧供需失衡。
三、急性过度通气影响血流动力学的变化,轻中度过度通气利于改善颅内高压引起的高血压作用。
四、S100B和CRP浓度变化能够反映大脑受损的程度,其变化与神经功能受损评分具有一致性。
五、重度过度通气对硬膜外血肿犬引起脑缺血可能因为脑血管过度收缩,脑细胞利用氧障碍、氧供需失衡等诸多因素综合作用的结果。
六、重度过度通气延迟颅内高压犬麻醉苏醒时间。
Mechanical ventilation plays an important role in medical practice,which involves in clinical anesthesia,ICU and resuscitation.Mechanical ventilation experenced a long time.In 1832,Dalziel developed a negative pressure breathing machine;In 1928, Driker-Shaw developed"iron lung".From then on,a new epoch of mechanical ventilation developed.Within about one century,mechanical ventilation successfully saved a lot of patients'lives.At the same time,more and more doctors thought highly of hyperventilation,but,a new problem occurred,a complication of mechanical ventilation, could produce some important effects on organisms.
Hyperventilation means a series of syndrome that ventilation produces once its role surpasses physiological need.When H_2CO_3 level of blood plasma decreased lower limit of normal(PaCO_2＜35mmHg) and PH＞7.45,as called respiratory alkalosis.Acute respiratory alkalosis means respiratory alkalosis takes place within 24 hours.About one century,medical scholars placed much energy to respiratory acidosis,but they paid little attention to respiratory alkalosis because respiratory alkalosis often existed mechanical ventilation and Hysteria Syndrome.At present clinical practice,hyperventilation is frequently used in induction of general anesthesia,extubation,laparoscopic operation,acute intracranial hypertension of trauma and so on,Especially in the traumatic intracranial hypertension.Hyperventilation is often used to reduce intracranial hypertension.Its role of lowering ICP depends on CO_2 chemical regulation in CNS.low CO_2 in blood makes Cerebral vessels constrict,which can reduce cerebral perfusion and ICP,thus,hyperventilation is frequently used to reduce bleeding during operation.
Morno-Kellie's principle points out that cranium content consists of brain tissue, cerebral blood volume and cerebrospinal fluid(CSF).Only both cerebral blood volume and CSF is spontaneously regulatable.The alteration of cranium content pressure mainly depends on cerebral blood volume and CSF.But,severe cerebral vasoconstriction does much harm to brain cells.Meanwhile,many studies demonstrated that hyperventilation not only induced cerebral ischemia but also brought wide physiological role such as kaliopenia,acid-base disturbance,etc.Even though many doctors agree on the fact that severe hyperventilation can produce cerbral ischemia,few doctors know how circulatory disorder of brain takes place and how suitable time of hyperventilation is.In addition,they really don't know how electrolytics alter when given hyperventilation.So we establish the intracranial hypertension model of extradural hematoma to make deep study on these problems.
Methods
25 healthy male dogs,received retro-grade jugular bulb venous catheterization and arterial catheterization,were randomly divided into 5 groups;A,B,C,D and E group(each=5).Dogs but A group were hyperventilated after epidural balloon inflation set up and built up animal model of introcranial hypertention by injecting 3-5ml 0.9%NS into lactoprene balloon of epidura.Dogs'P_(ET)CO_2 in B,C,D and E group will be maintained 32-45,25-32,25-20 and below 20 mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular jugular blood and femoral artery blood was taken suction respectively at different P_(ET)CO_2 period for measuring blood gas,VO_2,DO_2,ERO_2,lactic acid and blood sugar every 10 min when dogs'P_(ET)CO_2 chalks numerical value Booked.Vs,Vd,Vm,Pi and RI in MCA will be recorded by using Transcranial Doppler(TCD).Meanwhile,cerebral oxygen delivery/supply will be calculated according to blood gas analysis results.
1、Data and Grouping
25 Healthy male dogs,age from 2 to 4 years,body weight from 13 to 15.5Kg,will raise for one week,fasting for 12hrs,no drinking for 6hs.before experiment,are randomly divided into 5 groups(A、B、C、D and group E,each=5).Dogs in group A were placed a sacculus into epidural cavity but no inflatiing.The sacculus of dogs in any other groups was all inflated as the model of acute intracranial hypertension.All dogs were given 30min normal ventilation and P_(ET)CO_2 kept 32-45mmHg.
2、Anesthetizing and Monitoring
sodium pentobarbital according to 30mg/Kg was injected into abdominal cavity for anesthetizing dogs,and afterward intubation was operated.Internal jugular vein punctured under spontaneously breathing for monitoring CVP,infusing fluit and collecting blood.Femoral artery punctured for monitoring blood pressure and collecting blood.Multiparameter monitors continuosly detected body temperature, P_(ET)CO_2,HR,ECG,iBP and SPO_2.
3、Establishing dog's model of intracranial hypertension
Establish dog's model of intracranial hypertension by adopting epidural sacculus inflation.Place dogs to prone position,ambi-outer ear line 1cm distance between median line was drilled respectively.A trochar in left brain would be intubated to side ventricula to monitor ICP,and a foam rubber sacculus was placed into epidural cavity. Then,3～5ml 37℃physiological saline was injected into the sacculus within 60 seconds and kept ICP 60±3mmHg range.The symptoms of acute intracranial hypertension were as follows:side corediastasis,breathing alleviated or CT Image of occupyed Epidural.
4、Targets monitored
After kept acute intracranial hypertension for 3hs,0.8mg/kg vecuronium bromide I.v.then given mechanical ventilation.The dogs of group A,control group,without inflation.P_(ET)CO_2 in group A will be kept from 32 to 45mmHg under ventilatiing.Group B(normal breathing),group C(mild hyperventilation),group D(midrange hyperventilation) and group E(severe hyperventilation)set up the model of intracranial hypertension.After kept P_(ET)CO_2 normal level for 30min,P_(ET)CO_2 of B,C,D and group E would be kept 32-45,25-32,25-20 and below 20mmHg respectively for 60min by adjusting breathing parameters.0.5ml jugular blood and femoral artery blood was taken suction respectively every 10min in different P_(ET)CO_2 period for measuring blood gas,blood lactic acid and blood sugar.Meanwhile,4mL jugular blood will be collected in pre-inflation(T_1),post hyperventilation 2h(T_2),6h(T_3),12h(T_4) 24h(T_5) and 48h(T_6) for measuring content of S100B and CRP.drawn out hydatid fluid from balloon after hyperventilation.Neurological deficits scoring was evaluated at post hyperventilation 2h,6h and 12h.dogs would be put to death for pathological analysis at 48h.
5、Monitoring CBF
put detecting head of TCD to temple and adjust detecting head untill getting best signal of CMA.Vs、Vd、Vm、Pi and RI in MCA were recorded by using Transcranial Doppler in differently time.meanwhile O_2Ucc,A-VDO_2,Da-juL,ERO_2,Da-jvO_2 and Da-juglu will be calculated by blood gas value.
Results
Except group A,other any dogs were all established the model of intracranial hypertension and finished this experiment sucessfully.when sacculus inflated,Heart rate got slow,blood pressure increased,respirary frequency reduced and side pupil dilatated (P＜0.05) when compared with pre-inflation.
1、Blood gas analysis
With the hyperventilation development,K~+,Ca~(2+),PaCO_2 and HCO_3~-in arterial Blood decreased gradually.PH increased gradually,there existed a positive correlation between PaCO_2 and K~+.its coefficient correlation r=0.9196(P＜0.01).Coefficient correlation between PaCO_2 and Ca~(2+) r=0.9196(P＜0.01).CL~-,SaO_2 and Na~+ kept changeless(P＞0.05).PH decreased with hyperventlation,and got the lowest point 7.11±0.04(P＜0.05) when given severe hyperventilation.SjvO_2 in mild and midrange hyperventilation group kept changeless.But SjvO_2 in group D and group E got lowest point(42±6)%.
2、Blood Sugar and Lactic Acid
When compared with group A,Blood Sugar and Lactic Acid in experimental groups increased rapidly after inflation especially BS and Lac of jugular blood. Da-juglu increased(P＜0.05),Lactic acid in group mild hyperventilation decreased slightly,but severe hyperventilation makes BS and Lac increase(P＜0.05).Da-juL in group D increased sharply,there is significant difference between group A and group D (P＜0.05).
3、ICP and Hemodynamics
After balloon inflated,all dogs'HR decreased quickly,blood pressure and ICP increased.ICP increased from 13±3.4 mmHg in pre-operative to 60±3.0mmHg,there is significant difference when compared with pre-operation(P＜0.05).when value of P_(ET)CO_2 kept from 25 to 35mmHg,it revealed a positive coefficient correlation of PaCO_2 and ICP r=0.9958(P＜0.01).mild hyperventilation can reduce ICP slightly but its value is much higher than pre-opration.With severe hyperventilation development (P_(ET)CO_2＜20mmHg),ICP still kept changeless.
4、DO_2 and VO_2
When inflated,SjvO_2 dcreased quickly with P_(ET)CO_2.when P_(ET)CO_2＜20mmHg, SjvO_2 reached the lowest point.Da-jvO_2 decreased gradually with hyperventilation.but Da-jvO_2 in midrange hyperventilation increased significantly when compared with pre-operation or post-inflation(P＜0.05).ERO_2 in mild hyperventilation group changed slightly,but severe hyperventilation made ERO_2 decrease significantly when compared with pre-operation(P＜0.05).
5、Transcranial Doppler sonography(TCD)
After inflation,TCD showed Vs and Vd got slow greatly after epidural balloon expanded(P＜0.05).PI and RI increased significantly when compared with pre-trauma(P＜0.05).Athough Vs increased in mild hyperventilation,the value of PI and RI in B,C,D and E group grew higher than A group(P＜0.05).when P_(ET)CO_2＜25mmHg,Vs and Vd got its slowest point and showed much significant difference(P< 0.05) with P_(ET)CO_2 lowering.When P_(ET)CO_2＜25mmHg,Vs and Vd got its lowest point and kept changeless when hyperventilation deepened.
6、S100B and CRP
When inflated,S100B and CRP in experimental group increased at different degree (P＜0.05).S100B started to grow in 6h,peaked in 12h(2.08±0.32μg/L),decreased slightly in 24h.The value of S100 in group D grew more than pre-operation and other any groups(P＜0.05).CRP grew rapidly in 2h,peaked in 6h(21.8±2.5mg/L) untill 48h, there was significant difference when compared with pre-inflation(P＜0.05).CRP in group D grew most quickly of all groups,its value reached 29.4±5.7mg/L in T_5(P＜0.05).
7、Neurological Deficits Scoring(NDS)
After 2h hyperventilation,Neurological Deficits Scoring of all dogs was much high.their score decreased from time to time.NDS in severe hyperventilation group was higher in 2h and 6h than any other groups(P＜0.05 )but no significant difference in 12h(P＞0.05).There was no significant difference between group A,B and C at the sametime(P＞0.05).
8、Pathological analysis
Dogs's brain tissue of area compressed in experimental groups sofetened,swollen and blackened but other side brain tissue kept normal.Under light microscope,brain tissue in compressed area got necrosed mostly.and necrosis band extended to deep brain tissue and got lessened gradually in deep brain area.Necrosis cells in brain of group D diffused distribution.Necrosis was more wider than any other groups.Under electronical microscope,we can see the structure of the necrosis cells get blurred.Mitochondrium vacuolizated and dissolved.
Conclusions
1、Acute hyperventilation have much important effect on electrolytics and acid base,and it makes PH increase,K~+ and Ca~(2+) decrease.Blood K~+ reduced 0.5mmol/L and Blood Ca~(2+) reduced 0.05mmol/L when PaCO_2 reduced every 10mmHg.
2、When P_(ET)CO_2 kept from 25 to 35mmHg,ICP decreased with PaCO_2.when PaCO_2 exceed 35mmHg,ICP dcreased slightly;when PaCO_2 was reduced to 25 mmHg,cerebral ischemia could take place.Severe hyperventilation results in Disequilibrium of O_2 Supply/Need.
3、Acute hyperventilation have an important effect on hemodynamics of organism.mild and midrange hyperventilation alleviated hypertension brought about by acute intracranial hypertension.
4、Density of S100Band CRP shows the extent and level of injuried brain,their change have coincidence with NDS.
5、Severe hyperventilation resulted in cerebral ischemia lies in Cerebral vessels constricted exceptionally,and obstacle of brain's oxygen intaking plays an important role in cerbral ischemia also.
6、Severe hyperventilation delayed palinessthesia time of dogs with acute intracranial hypertension.
引文
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2 Van KaamAH,Rimensberger PC.Lung-protective ventilation strategies in neonatology:What do we know-What do we need to know? Crit Care Med.2007:1:23.
3 Macdonale RL,Mojtahedi S,Johns L,et al.Randomized comparisonof Guglielmi Detachable Coils and cellulose acetate polymer for treatment of aneurysms in dogs.Stroke.1998:29:478-486.
4 王忠诚.王忠诚神经外科学.武汉:湖北科学技术出版社,2005.3;1.123-223.
5 Perez A,Minces PG,Schnitzler EJ,et al.Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury.Pediatr Crit Care Med.2003;4:33-38.
6 Kubo T,Nakagawa I,Hidaka S,et al.Relationship between regional cerebrovascular oxygen saturation and jugular bulb oxygen saturation during carotid endarterectomy Masui.2005;54:1104-1108.
7 Mihci E,Dora B,Balkan S.Transcranial doppler ultrasonographic evaluation of cerebral circulation during passive tilting in patients with Parkinson's disease.J Clin Ultrasound.2007.12:35(3):138-143.
8 Oertel M,Kelly DF,Lee JH,et al.Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury.J Neurosurg.2002;97:1045-1053.
9 Guzman JA,Kruse JA.Splanchnic hemodynamics and gut mucosal-arterial PCO_2gradient during systemic hypocapnia.J Appl Physiol.1999:87:1102-1106
10 王恩真主编.神经外科醉.人民卫生出社.2000;8:125-233.
11 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traumatol.2000;15:210-213.
12 Vannucci RC,Towfighi J,Bruchlacher RM,et al.Effectof extreme hypercapnia on hypoxic-ischaemic brain damage in the immature rat.Pediatr Res.2001:49:799-803.
13 Steiner LA,Balestreri M,Johnston AJ,et al.Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
14 张赛,杨树源,王明路.重型脑外伤急性期低氧血症及其相关因素探讨.中华神经外科杂志.1997;1:53-56.
15 Delilovic-Vranic J.Transcranial Doppler sonography as diagnostic method.Bosn J Basic Med Sci.2002;2:66-70.
1 Grocott HP,Croughwell ND,Amory DW,et al.Cerebral emboli and serum S100beta during cardiac operations[J].Ann Thorac Surg.1998;65:1645-1649.
2 Mackay GM,Forrest CM,Stoy N,et al.Tryptophan metabolism and oxidative stress in patients with chonic brain injury.Eur J Neurol.2006;13:30-42.
3 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol,2001;33:637-668.
4 郭毅,姜昕,陈实,等.C-反应蛋白缺血性脑卒中预后的重要标志物.中华预防医学杂志.2003;3:102-104.
5 施新猷主编.现代医学实验动物学.北京:人民军医出版社.2000;119-132.
6 邓丽云,赵嘉训,赵真英,等.截流式肺泡二氧化碳监测的可行性.中华麻醉学杂志,2004;24:392-393.
7 林江凯,王宪荣.急性颅内压增高时肺动静脉分流的意义.中华实验外科杂志,2003;8:687-688.
8 Zhou Y,Wang D,Du M,et al.Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs.Can J Anaesth.1998;45:692-698.
9 Liu Y,Rosenthal RE,Haywood Y,et al.Normoxic ventilation after cardiac arrest reduces oxidation of brain lipids and improves neurological outcome.Stroke.1998;29:1679-1686.
10 Vannucci RC,Towfighi J,Brucklacher RM,et al.Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat.Pediatr Res,2001;49:799-803.
11 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traumatol,2000;3:210-213.
12 Sawauchi S,Taya K,Murakami S,et al.Serum S-100B protein and neuron-specific enolase after traumatic brain injury.No Shinkei Geka.2005;33(11).1073-1080.
13 Eriksen JL,Gillespie R,Druse MJ.Effects of ethanol and 5-HTIA agonists on astroglial SIOOB.Brain Res Dev Brain Res,2002:139:97-105.
14 裴惠临.郭清莲.双抗体夹心法检测血清S一100蛋白及其临床意义.武汉大学学报(医学版).2004;25:72-73.
15 SchuhmannMU,Ostrowski KR,Draper EJ,et al.The value of C-reactive protein in the management of shunt infections.J Neurosurg,2005;103:223-230.
16 Steiner LA,Balestreri M,Johnston AJ,et al.Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
1 Grocott HP,Croughwe11 ND,Amory DW,et al.Ann Thorac Surg.1998:65:1645-1650.
2 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol.2001:33:637-668.
3 邓丽云,赵嘉训,赵真英,等.截流式肺泡二氧化碳监测的可行性.中华麻醉学杂志.2004;24:392-393.
4 Vannucci RC,Towfighi J,Bruchlacher RM,et al.Effectof extreme hypercapnia on hypoxic-ischaemic brain damage in the immature rat.Pediatr Res.2001:49:799-803.
5 王恩真主编.神经外科麻醉学.人民卫生出版社.2000;8:1.
6 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traamatol.2000.15:3:210-213.
7 Sawauchi S,Taya K,Murakami S,et al.Serum S-IOOB protein and neuron-specific enolase after traumatic brain injury.2005:33:1073-1080.
8 凌四海,郭实士,翁永振,等.精神分裂症患者血浆S-100B的研究.临床检验杂志.2002;20:151-152.
9 Steiner LA,BalestreriM,JohnstonAJ,et al Effects of moderatehyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
10 张赛,杨树源,王明路.重型脑外伤急性期低氧血症及其相关因素探讨.中华神经外科杂志.1997;1:53-54.
1 Nakayama H,Smith CA,Rodman JR.et al.Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep.Am J Respir Crit Care Med.2002:165:1251-1260.
2 Decaux G,Musch W,Penninckx R,et al.Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency.J Clin Endocrinol Metab.2003:88:5255-5257.
3 Marion DW,Puccio A,Wisniewski SR,et al.Effect of hyperventilation on extracellular concentrations of glutamate,lactate,pyruvate,and local cerebral blood flow in patients with severe traumatic brain injury.Crit Care Med.2002:30:2619-2625.
4 DiringerMN,Videen TO,Yundt K,et al..Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.J Neurosurg.2002:96:103-108.
5 Bulock R,Chesnut RM,Clilion C,et al.Guidelines for the management of severe traumatic brain injury.J Neurotrauma,2000:17:451.
6 Bobrinskaia IG,Levite EM,Iminova KhM,et al.Effect of hyperventilation on the cerebral blood flow and metabolism in patients with craniocerebral trauma.Anesteziol Reanimatol.2002;3:59-63.
7 Stacd,ettiN,Rosei S.Intracranial hypedeasim in head injury:management and rlulta.Intenn va Care Med,1999:25:371.
8 傅艳妮,彭书凌,岑燕遗.过度通气对脑氧供需平衡的影响.临床麻醉学杂志.2003;19:622-623.
9 唐伟泰,梁庆芝.过度通气对重型颅脑损伤患者脑氧供需平衡的影响.广东医学.2004:25:151-153.
10 孟丽巍,袁振红,王静等.过度通气对脑血流脑代谢颅内压影响的临床研究.中国急救医学.2002;22:623-625.
11 兰天,谢建,龚志刚.38例脑外伤血、脑脊液酸碱气体分析.中华神经外科杂志,1997: 3:123.
12 Gopinath SP,Cormio M,Ziegher J,et al.Intraoperative jugularvenous desaturation during surgery for traumatic intracranial hematomas(J).Anesth Analg,1996:83:1014-1021.
13 Oertel M,Kelly DF,Lee JH,et al.Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury.J Neurosurg.2002:97:1045-1053.
14 高晋健,唐文渊.重型脑损伤局部脑氧饱和度变化及影响因素.中华创伤杂志.1999:15:169-171.
15 Gopinath SP,Valadka AB,Uzra M,et al.Comparison of jugular venous oxygen saturation and brain tissue P02 a monitor of cerebral ischemia after head injury.Crit Care Med.1999:29:2337-2345.
16 杨术真,李丽娜,李拴德等.血清转化生长因子TCF-β1变化与颅脑损伤患儿预后关系.中国临床神经科学.2004;12:296-297.
17 Shaaban A,Harmer M,Vaughan R,Senim SIO0 protein as a marker of cerebral damage during cardiac surgery.Br J Anesth.2000:85:287-298.
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20 李立莎,程斌.高通气综合征临床分析.中华实用医药杂志.2004;6:412.
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25 Simchen MJ,Tesler J,Azami T,Effects of maternal hyperoxia with and without normocapnia in uteroplacental and fetal Doppler studies.Ultrasound Obstet Gynecol.2005:26:495-499.
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27 Schleifer LM,Ley R,Spalding TW.A hyperventilation theory of job stress and musculoskeletal disorders.Am J Ind Med.2002;41:420-432.
28 林献忠,林健清,林群等.CO2气腹对呼吸循环功能的影响及过度通气的应用.华中医学杂志.2002;26:271-273.
29 王纯辉,李元海,徐志荣等.过度通气对腹腔镜手术C02气腹前后PetCO2及动脉血气的影响.安徽医科大学学报.2002;37:309-310.
1 Eat WS,Claus WH.The SIO0 family of EF-hand calcium binding proteins:functions and pathology.Trends in Biochem Sci.1996:21:134-140.
2 Eriksen JL,Gillespie R,Druse MJ.Effects of ethanol and 5-HTiAagonists on astroglial SIOOB.Brain Res Dev Brain Res.2002;139:97-105.
3 Rothermundt M,Missler U,Arolt V,et al.Increased SIOOB blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology.Moi Psychiatry.2001:6:445-449.
4 Eizmann CW,Cox JA.New perspectives on SlO0 proteins:a multi-functional Ca(2+)-,Zn(2+)-and Cu(2+)-binding protein family.Biometals.1998:11:383-397.
5 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol.2001:33:637-668.
6 裴惠临.郭清莲.双抗体夹心法检测血清S-100蛋白及其临床意义.武汉大学学报(医学版).2004:25:72-73.
7 Rothermundt M,Peters M,Prehn JH,et al.SIOOB in brain damage and neurodegeneration.Microsc Res Tech.2003:60:614-632.
8 Van Eldik LJ,Wainwright MS.The Janus face of glial-derived SIOOB:beneficial and detrimental functions in the brain.Restor Neurol Neurosci.2003:21:97-108.
9 Abdesselam O,Vally J,Adem C,et al.Reference values for serum S-100B protein depend on the race of individuals.Clin Chem.2003:49:836-837.
10 Rothermundt M,Peters M,Prehn JH,et al,SIOOB in brain damage and neurodegeneration.Microsc Res Tech.2003:60:614-632.
11 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol.2001:33:637-668.
12 Mussack T,Biberthaler P,Kanz KG,et al.Immediate S-100B and neuron-specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated,minor head-injured patients.Shock.2002:18:395-400.
13 Georgiadis D,Berger A,Kowatschev E,et al.Predictive value of S100β and neuron specific enolase levels for adverse neurologic outcome after cardiac surgery.J Thorac Cardiovasc Surg.2000:119-138.
14 凌四海,郭实士,翁永振,等.精神分裂症患者血浆S-100B的研究.临床检验杂志.2002:20:151-152.
15 Buttner T,Weyers S,Postert T,et al.S100 protein:serum marker of focal brain damage after ischemic territorial MCA infarction.Stroke.1997:28:1961-1965.
16 Persson L,Hardemark HG,Gustafsson J,et al.S100 protein and neuron specific enolase in cerebrospinal fluid and serum:markers of cell damage in human central nervous system.Stroke.1997:18:911-918.
17 Woertgen C,Rothoerl RD,Holzschuh M,et al.Comparison of serial S100 and NSE serammeasurements after severe head injury.Acta Neurochirurgica.1997:139:1161-1165.
18 Elting JW,de Jager AE,Teelken AW,et al.Comparison of serum S-100 protein levels following stroke and traumatic brain injury.J Neurol Sci.2000:181:104-110.
2 Van KaamAH,Rimensberger PC.Lung-protective ventilation strategies in neonatology:What do we know-What do we need to know? Crit Care Med.2007:1:23.
3 Macdonale RL,Mojtahedi S,Johns L,et al.Randomized comparisonof Guglielmi Detachable Coils and cellulose acetate polymer for treatment of aneurysms in dogs.Stroke.1998:29:478-486.
4 王忠诚.王忠诚神经外科学.武汉:湖北科学技术出版社,2005.3;1.123-223.
5 Perez A,Minces PG,Schnitzler EJ,et al.Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury.Pediatr Crit Care Med.2003;4:33-38.
6 Kubo T,Nakagawa I,Hidaka S,et al.Relationship between regional cerebrovascular oxygen saturation and jugular bulb oxygen saturation during carotid endarterectomy Masui.2005;54:1104-1108.
7 Mihci E,Dora B,Balkan S.Transcranial doppler ultrasonographic evaluation of cerebral circulation during passive tilting in patients with Parkinson's disease.J Clin Ultrasound.2007.12:35(3):138-143.
8 Oertel M,Kelly DF,Lee JH,et al.Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury.J Neurosurg.2002;97:1045-1053.
9 Guzman JA,Kruse JA.Splanchnic hemodynamics and gut mucosal-arterial PCO_2gradient during systemic hypocapnia.J Appl Physiol.1999:87:1102-1106
10 王恩真主编.神经外科醉.人民卫生出社.2000;8:125-233.
11 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traumatol.2000;15:210-213.
12 Vannucci RC,Towfighi J,Bruchlacher RM,et al.Effectof extreme hypercapnia on hypoxic-ischaemic brain damage in the immature rat.Pediatr Res.2001:49:799-803.
13 Steiner LA,Balestreri M,Johnston AJ,et al.Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
14 张赛,杨树源,王明路.重型脑外伤急性期低氧血症及其相关因素探讨.中华神经外科杂志.1997;1:53-56.
15 Delilovic-Vranic J.Transcranial Doppler sonography as diagnostic method.Bosn J Basic Med Sci.2002;2:66-70.
1 Grocott HP,Croughwell ND,Amory DW,et al.Cerebral emboli and serum S100beta during cardiac operations[J].Ann Thorac Surg.1998;65:1645-1649.
2 Mackay GM,Forrest CM,Stoy N,et al.Tryptophan metabolism and oxidative stress in patients with chonic brain injury.Eur J Neurol.2006;13:30-42.
3 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol,2001;33:637-668.
4 郭毅,姜昕,陈实,等.C-反应蛋白缺血性脑卒中预后的重要标志物.中华预防医学杂志.2003;3:102-104.
5 施新猷主编.现代医学实验动物学.北京:人民军医出版社.2000;119-132.
6 邓丽云,赵嘉训,赵真英,等.截流式肺泡二氧化碳监测的可行性.中华麻醉学杂志,2004;24:392-393.
7 林江凯,王宪荣.急性颅内压增高时肺动静脉分流的意义.中华实验外科杂志,2003;8:687-688.
8 Zhou Y,Wang D,Du M,et al.Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs.Can J Anaesth.1998;45:692-698.
9 Liu Y,Rosenthal RE,Haywood Y,et al.Normoxic ventilation after cardiac arrest reduces oxidation of brain lipids and improves neurological outcome.Stroke.1998;29:1679-1686.
10 Vannucci RC,Towfighi J,Brucklacher RM,et al.Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat.Pediatr Res,2001;49:799-803.
11 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traumatol,2000;3:210-213.
12 Sawauchi S,Taya K,Murakami S,et al.Serum S-100B protein and neuron-specific enolase after traumatic brain injury.No Shinkei Geka.2005;33(11).1073-1080.
13 Eriksen JL,Gillespie R,Druse MJ.Effects of ethanol and 5-HTIA agonists on astroglial SIOOB.Brain Res Dev Brain Res,2002:139:97-105.
14 裴惠临.郭清莲.双抗体夹心法检测血清S一100蛋白及其临床意义.武汉大学学报(医学版).2004;25:72-73.
15 SchuhmannMU,Ostrowski KR,Draper EJ,et al.The value of C-reactive protein in the management of shunt infections.J Neurosurg,2005;103:223-230.
16 Steiner LA,Balestreri M,Johnston AJ,et al.Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
1 Grocott HP,Croughwe11 ND,Amory DW,et al.Ann Thorac Surg.1998:65:1645-1650.
2 Donato R.S100:a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles.Int J Biochem Cell Biol.2001:33:637-668.
3 邓丽云,赵嘉训,赵真英,等.截流式肺泡二氧化碳监测的可行性.中华麻醉学杂志.2004;24:392-393.
4 Vannucci RC,Towfighi J,Bruchlacher RM,et al.Effectof extreme hypercapnia on hypoxic-ischaemic brain damage in the immature rat.Pediatr Res.2001:49:799-803.
5 王恩真主编.神经外科麻醉学.人民卫生出版社.2000;8:1.
6 Bao Y,Jiang J,Zhu C,et al.Effect of hyperventilation on brain tissue oxygen pressure,carbon dioxide pressure,pH value and intracranial pressure during intracranial hypertension in pigs.Chin J Traamatol.2000.15:3:210-213.
7 Sawauchi S,Taya K,Murakami S,et al.Serum S-IOOB protein and neuron-specific enolase after traumatic brain injury.2005:33:1073-1080.
8 凌四海,郭实士,翁永振,等.精神分裂症患者血浆S-100B的研究.临床检验杂志.2002;20:151-152.
9 Steiner LA,BalestreriM,JohnstonAJ,et al Effects of moderatehyperventilation on cerebrovascular pressure-reactivity after head injury.Acta Neurochir Suppl.2005;95:17-20.
10 张赛,杨树源,王明路.重型脑外伤急性期低氧血症及其相关因素探讨.中华神经外科杂志.1997;1:53-54.
1 Nakayama H,Smith CA,Rodman JR.et al.Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep.Am J Respir Crit Care Med.2002:165:1251-1260.
2 Decaux G,Musch W,Penninckx R,et al.Low plasma bicarbonate level in hyponatremia related to adrenocorticotropin deficiency.J Clin Endocrinol Metab.2003:88:5255-5257.
3 Marion DW,Puccio A,Wisniewski SR,et al.Effect of hyperventilation on extracellular concentrations of glutamate,lactate,pyruvate,and local cerebral blood flow in patients with severe traumatic brain injury.Crit Care Med.2002:30:2619-2625.
4 DiringerMN,Videen TO,Yundt K,et al..Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.J Neurosurg.2002:96:103-108.
5 Bulock R,Chesnut RM,Clilion C,et al.Guidelines for the management of severe traumatic brain injury.J Neurotrauma,2000:17:451.
6 Bobrinskaia IG,Levite EM,Iminova KhM,et al.Effect of hyperventilation on the cerebral blood flow and metabolism in patients with craniocerebral trauma.Anesteziol Reanimatol.2002;3:59-63.
7 Stacd,ettiN,Rosei S.Intracranial hypedeasim in head injury:management and rlulta.Intenn va Care Med,1999:25:371.
8 傅艳妮,彭书凌,岑燕遗.过度通气对脑氧供需平衡的影响.临床麻醉学杂志.2003;19:622-623.
9 唐伟泰,梁庆芝.过度通气对重型颅脑损伤患者脑氧供需平衡的影响.广东医学.2004:25:151-153.
10 孟丽巍,袁振红,王静等.过度通气对脑血流脑代谢颅内压影响的临床研究.中国急救医学.2002;22:623-625.
11 兰天,谢建,龚志刚.38例脑外伤血、脑脊液酸碱气体分析.中华神经外科杂志,1997: 3:123.
12 Gopinath SP,Cormio M,Ziegher J,et al.Intraoperative jugularvenous desaturation during surgery for traumatic intracranial hematomas(J).Anesth Analg,1996:83:1014-1021.
13 Oertel M,Kelly DF,Lee JH,et al.Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury.J Neurosurg.2002:97:1045-1053.
14 高晋健,唐文渊.重型脑损伤局部脑氧饱和度变化及影响因素.中华创伤杂志.1999:15:169-171.
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