1、呼吸机治疗的肺保护策略呼吸机治疗的肺保护策略浙江大学医学院附属儿童医院浙江大学医学院附属儿童医院施丽萍施丽萍呼吸机相关性肺损伤呼吸机相关性肺损伤 acute parenchymal lung injury and an acute inflammatory response in the lung. cytokines alveoli and the systemic circulation multiple organ dysfunction mortality呼吸机相关性肺损伤呼吸机相关性肺损伤ventilator-induced lung injury 容量性损伤容量性损伤 Volutr
2、auma（large gas volumes ） 压力性损伤压力性损伤 Barotrauma（high airway pressure ） 不张性损伤不张性损伤 Atelectotrauma（alveolar collapse and re-expansion） 生物性损伤生物性损伤 Biotrauma（increased inflammation ）肺肺 损损 伤伤 病病 理理 alveolar structural damage pulmonary edema、 inflammation、 fibrosis surfactant dysfunction other organ dysfun
3、ction exacerbate the disturbance of lung development Semin Neonatol. 2002 Oct;7(5):353-60. Approaches in the management of acute respiratory failure in childrenprotective ventilatory and potential protectiveventilatory modes lower tidal volume and PEEP permissive hypercapnia high-frequency oscillato
4、ry ventilation airway pressure release ventilation partial liquid ventilationimprove oxygenation recruitment maneuvers prone positioning kinetic therapy reduce FiO2 and facilitate gas exchange inhaled nitric oxide and surfactant Curr Opin Pediatr. 2004 Jun;16(3):293-8.Can mechanical ventilation stra
5、tegies reduce chronic lung disease? continuous positive airway pressure permissive hypercapnia patient-triggered ventilation volume-targeted ventilation proportional assist ventilation high-frequency ventilation Semin Neonatol. 2003 Dec;8(6):441-8小潮气量和呼气末正压小潮气量和呼气末正压 lower tidal volume and PEEPVenti
6、lation with lower tidal volumes versus traditional tidal volumes in adults for ALI and ARDS 1202 patients lower tidal volume (7ml/kg) low plateau pressure 30 cm H2O versus tidal volume 10 to 15 ml/kg Mortality at day 28 long-term mortality was uncertain low and conventional tidal volume with plateau
7、 pressure 31 cm H2O was not significantly different Cochrane Database Syst Rev. 2004;(2):CD003844Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome 549 patients acute lung injury and ARDS lower-PEEP group 8.33.2cmH2O higher-PEEP group 13.23
8、.5cmH2O (P0.001). tidal-volume 6ml/kg end-inspiratory plateau-pressure30cmH2O The rates of death 24.9 % 27.5 % (p=0.48) From day 1 to day 28, breathing was unassisted 14.510.4 days 13.810.6 days (p=0.5) clinical outcomes are similar whether lower or higher PEEP levels are used. N Engl J Med. 2004 Ju
9、l 22;351(4):327-36.Increasing inspiratory time exacerbates ventilator-induced lung injury during high-pressure/high-volume mechanical ventilation Sprague-Dawley rats negative control group low pressures (PIP = 12 cm H2O), rate = 30, iT = 0.5, 1.0, 1.5secs experimental groups high pressures (PIP = 45
10、 cm H2O), rate = 10, iT = 0.5 , 1.0 , 1.5 secs lung compliance, PaO2 /FiO2 ratio, wet/dry lung weight, and dry lung/body weight as inspiratory time increased ,static lung compliance (p =.0002) and Pao2/Fio2 (p =.001) decreased. Wet/dry lung weights (p .0001) and dry lung/body weights (p 0.050.050.05
11、0.050.05对照组（对照组（NPM)： 应用人工呼吸机限压定时持续气流型，通气模应用人工呼吸机限压定时持续气流型，通气模式为式为IMV，持续脉搏血氧饱和度监测使其维持，持续脉搏血氧饱和度监测使其维持在在8595%，每，每8h监测动脉血气一次，要求血监测动脉血气一次，要求血气维持在正常范围内，气维持在正常范围内，PaO2 40-70mmHg, PaCO2 35-45mmHg观察组（观察组（PM组）组）： 1、肺力学监测仪、肺力学监测仪(Bicore CP100)每每812h 监测监测一次机械通气时肺力学参数一次机械通气时肺力学参数 2、监测时要求患儿与呼吸机完全同步或无自、监测时要求患儿与呼
12、吸机完全同步或无自主呼吸状态（必要时通过药物抑制呼吸）主呼吸状态（必要时通过药物抑制呼吸） 3、肺力学监测仪的传感器置于近端接口、肺力学监测仪的传感器置于近端接口 4、气管插管气漏率小于、气管插管气漏率小于20% 5、每监测一次持续、每监测一次持续0.51h至数据稳定后记录至数据稳定后记录监测的数据监测的数据NPM 组和组和PM组的评估指标组的评估指标 1. 疾病极期，即生后疾病极期，即生后2448h时呼吸机要求最高时呼吸机要求最高值，包括值，包括FiO2、 PIP、PEEP、Ti、MAP、VR 2. VE、C20/C、TC（限于（限于PM组），组）， 3. 记录血记录血pH、PaO2、PaC
13、O2、氧合指数（、氧合指数（OI ）（OI=FiO2MAP/PaO2）和心率、血压和心率、血压 4. 呼吸机应用时间，用氧时间，住院天数，病呼吸机应用时间，用氧时间，住院天数，病死率，死率，PDA，IVH和呼吸机相关性肺损伤的发和呼吸机相关性肺损伤的发生率。生率。两组呼吸机参数比较两组呼吸机参数比较 FiO2（%） PIP（cmH2O) P E E P（cmH2O)MAP（cmH2O) Ti (sec) VR（次（次/分）分）NPM601930.53.45.60.814.93.40.750.1399PM621826.71.75.40.611.92.00.450.14210t0.1847.527
14、1.3395.81818.101.81p0.050.050.0010.05PIP30.526.705101520253035NPMPMPIPMAP14.911.90246810121416NPMPMMAPMAP14.911.90246810121416NPMPMMAPPEEP5.65.40123456NPMPMPEEP两组血气监测结果比较两组血气监测结果比较 PHPaO2(mmHg)PaCO2 (mmHg)HR(次次/分）分）BP(mmHg)OINPM7.310.1571740101448404.61913PM7.30.045916486.31456393.6147.7t0.2890.5164
15、.6630.7980.9422.011p0.050.050.050.050.05pH7.317.377.17.27.37.47.5NPMPMpHPaO25759010203040506070NPMPMPaO2PaCO240480102030405060NPMPMPaCO2PaCO240480102030405060NPMPMPaCO2两组呼吸机相关性肺损伤、两组呼吸机相关性肺损伤、PDA、IVH、呼吸机应用时间、用氧时间、住院天数、病死率比较呼吸机应用时间、用氧时间、住院天数、病死率比较 VALI%PDA%IVH%IMV(d)用氧时用氧时间间(d)住院天住院天数数(d)病死率病死率%NPM32
16、36423.91.8117191414PM13.333.3404.21.713722118.3t 0.8671.4741.22 5.570.090.05 0.9p0.050.050.050.050.050.05结论结论 肺力学监测能指导正确应用呼吸机，降低呼吸肺力学监测能指导正确应用呼吸机，降低呼吸机相关性肺损伤机相关性肺损伤 从本研究结果推荐从本研究结果推荐RDS呼吸机应用的参数为：呼吸机应用的参数为：PIP 25cmH2O左右，短左右，短Ti 0.30.5秒，应用适当秒，应用适当的的PEEP 5-7cmH2O治疗治疗RDS，不影响氧合。，不影响氧合。 PaCO2的轻度增高的轻度增高（PaC
17、O2 45-60），），IVH的的发生未见增加。发生未见增加。 允许性高碳酸血症允许性高碳酸血症Permissive hypercapniaPermissive hypercapnia-role in protective lung ventilatory strategies First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlyin
18、g these effects Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation Third, we consider whether direct elevation of CO2, in the absence of protective ventilation, is beneficial or deleterious Fourth, we address the current eviden
19、ce regarding the buffering of hypercapnic acidosis Lung-protective ventilation in acute respiratory distress syndrome: protection by reduced lung stress or by therapeutic hypercapnia? hypercapnic acidosis lung-protective ventilation respiratory acidosis protected the lung The protective effect of re
20、spiratory acidosis inhibition of xanthine oxidase prevented by buffering the acidosis . the protection resulted from the acidosis rather than hypercapnia Am J Respir Crit Care Med. 2000 Dec;162(6):2021-2. Permissive hypercapnia in ARDS and its effect on tissue oxygenation The right-shift of the haem
21、oglobin-oxygen dissociation curve reduce intrapulmonary shunt (Qs/Qt) by potentiating hypoxic pulmonary vasoconstriction affect the distribution of systemic blood flow both within organs and between organs Acta Anaesthesiol Scand Suppl. 1995;107:201-8 Hypercapnic acidosis attenuates endotoxin induce
22、d acute lung injuryattenuated the decrement in oxygenation improved lung compliancereduced alveolar neutrophil infiltration and histologic indices of lung injury Am J Respir Crit Care Med. 2004 Jan 1;169(1):46-56Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury
23、 12 rabbits ventilator-induced lung injury (VILI) PaCO2 40 mm Hg n = 6 PaCO2 80-100 mm Hg n = 6 respiratory mechanics (plateau pressures) 27.0 2.5 20.9 3.0 p = 0.016 gas exchange (PaO2 ) 165.2 19.4 77.3 87.9 p = 0.02 wet:dry weight 9.7 2.3 6.6 1.8 p = 0.04 bronchoalveolar lavage fluid protein concen
24、tration 1350 228 656 511 p = 0.03 cell count 6.86 x 105 2.84 x 105 p = 0.021 injury score 7.0 3.3 0.7 0.9 p 0.0001 Am J Respir Crit Care Med. 2002 Aug 1;166(3):403-8 Effects of high PCO2 on ventilated preterm lamb lungs Preterm surfactant-treated lambs with a high tidal volume (Vt) 30 min acute lung
25、 injury. Vt 6-9 mL/kg 5.5 h PCO2 40-50 mm Hg add to the ventilator circuit PCO2 95 5 mm Hg heart rates blood pressures plasma cortisol values oxygenation no different white blood cells hydrogen peroxide production IL-1beta, IL-8 cytokine mRNA expression in cells from the alveolar wash Histopathology
26、 less lung injury Pediatr Res. 2003 Mar;53(3):468-72.Permissive hypercapnia for the prevention of morbidity and mortality in mechanically ventilated newborn infants Two trials involving 269 newborn infants no evidence the incidence of death or CLD at 36 weeks (RR 0.94, 95% CI 0.78, 1.15) no evidence
27、 IVH 3 or 4 (RR 0.84, 95% CI 0.54, 1.31) no evidence PVL (RR 1.02, 95% CI 0.49, 2.12). no evidence Long term neurodevelopmental outcomes One trial reported that permissive hypercapnia reduced the incidence of CLD in the 501 to 750 gram subgroup Cochrane Database Syst Rev. 2001;(2):CD002061Permissive
28、 hypercapnia in neonates: the case of the good, the bad, and the ugly PaCO2 levels of 45-55 mmHg in high-risk neonates are safe and well tolerated Pediatr Pulmonol. 2002 Jan;33(1):56-64高频震荡通气高频震荡通气High-frequency oscillatory ventilation High-frequency oscillatory ventilation for acuterespiratory dist
29、ress syndrome in adult patients148 randomized, controlled trial ARDS HFOV PCV PaO2/FiO2 72h no Thirty-day mortality 37% or 52% (p=0.102) barotrauma, hemodynamic instability, or mucus plugging no different clinical use in adults FiO260% and MAP 20 cm H2O or PEEP15 cm H2O Crit Care Med. 2003 Apr;31(4
30、Suppl):S317-23Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants updated in May 2003 3275 Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction no evidence o
31、f effect on CLD and mortality at 28-30 days Pre-specified subgroup analyses Short term neurological morbidity Grade 3 or 4 IVH and PVL (no using high volume strategy) Cochrane Database Syst Rev. 2003(4):CD000104Open lung ventilation improves gas exchange and attenuates secondary lung injury in a pig
32、let model of meconium aspiration Prospective, randomized animal study 36 newborn piglets (6 saline controls) PPV(OLC), HFOV(OLC), PPV(CON) ventilated for 5 hrs bronchoalveolar lavage fluid myeloperoxidase activity lung injury score Alveolar protein influx no different superior oxygenation and less v
33、entilator-induced lung injury Crit Care Med. 2004 Feb;32(2):443-9Changes in mean airway pressure during HFOV influences cardiac output in neonates and infants 14 patients 1 year weight 10 kg HFOV study group (n = 9) MAP +5 and -3 cmH2O control group (n = 5) Cardiac output echocardiography Doppler te
34、chnique Cardiac output the study group (P = 0.02) the greatest change at the highest Paw at -11% (range: -19 to -9) compared with baseline. Acta Anaesthesiol Scand. 2004 Feb;48(2):218-23Randomized trial of high-frequency oscillatory ventilation versus conventional ventilation:effect on systemic bloo
35、d flow in very preterm infants 43 infants 29w 8 kg Vital signs, airway pressures, minute ventilation, Spo(2), and E(T)CO(2) were recorded APRV provided similar ventilation, oxygenation, mean airway pressure, hemodynamics, and patient comfort as SIMV APRV significantly lower inspiratory peak and plat
36、eau pressures Pediatr Crit Care Med. 2001 Jul;2(3):243-6Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome 58 patients randomized APRV or SIMV PIP at APRV-group (25.9 0.6 vs. 28.6 0.7 cmH2O) (P = 0.007). no different PEEP and physiological variab
37、les (PaO2/FiO2, PaCO2, pH, minute ventilation, mean arterial pressure, cardiac output) At day 28, the number of ventilator-free days was similar (13.4 1.7 , 12.2 1.5), the mortality (17% and 18%) APRV did not differ from SIMV with PS in clinically relevant outcome Acta Anaesthesiol Scand. 2004 Jul;48(6):722-31APRVNo evidence to indicate that APRV is better than conventional ventilation
