ARDS de  Koruyucu Ventilasyon Stratejilerinin Hastaya G re Uyarlanmasi

ARDS de Koruyucu Ventilasyon Stratejilerinin Hastaya G re Uyarlanmasi PowerPoint PPT Presentation


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Akut Solunum Sikintisi Sendromu (ARDS). Alveol-kapiller membranda permeabilite artisiDiff

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ARDS de Koruyucu Ventilasyon Stratejilerinin Hastaya G re Uyarlanmasi

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1. ARDS’de Koruyucu Ventilasyon Stratejilerinin Hastaya Göre Uyarlanmasi Dr. Kubilay Demirag Ege Üniversitesi Tip Fakültesi Anesteziyoloji ve Reanimasyon AD

2. Akut Solunum Sikintisi Sendromu (ARDS) Alveol-kapiller membranda permeabilite artisi Diffüz alveol hasari Proteinden zengin alveol ödemi Bu patolojik degisikliklere eslik eden fizyolojik degisiklikler: Ciddi hipoksemi (genellikle oksijen tedavisine dirençli) Kompliansta azalma Ilk kez 37 yil önce Dr. Thomas Petty tarafindan tanimlanan akut solunum sikintisi sendromu(ARDS) alveolo- kapiller membran permeabilitesinde artma, diffüz alveolar hasar ve proteinden zengin sivinin akümülasyonuna bagli alveolar ödem ile karakterize bir sendromdur. Bu patolojik degisiklikler ciddi hipoksemi ve pulmoner kompliansta azalmayi da içeren çesitli fizyolojik degisikliklerle birliktedir. Ilk kez 37 yil önce Dr. Thomas Petty tarafindan tanimlanan akut solunum sikintisi sendromu(ARDS) alveolo- kapiller membran permeabilitesinde artma, diffüz alveolar hasar ve proteinden zengin sivinin akümülasyonuna bagli alveolar ödem ile karakterize bir sendromdur. Bu patolojik degisiklikler ciddi hipoksemi ve pulmoner kompliansta azalmayi da içeren çesitli fizyolojik degisikliklerle birliktedir.

3. Terminoloji Travmatik islak akciger Konjestif atelektazi Eriskin solunum sikintisi sendromu (ARDS) Sok akcigeri Da Nang akcigeri Transfüzyon akcigeri Post-perfüzyon akcigeri Petty TL. In: Acute Respiratory Distress Syndrome (Matthay MA ed). Marcel Dekker, Inc., New York, 2003, pp:1-6. ARDS I. Dünya savasi srasinda savas yaralilarinda ani kollaps ve solunumsal ölüme yol açan dramatik olarak progressif klinik katastrof olarak ortaya çikmistir.Daha sonra her tip travmaya bagli olarak gelisen pulmoner ödeme yol açan akciger hasarina Travmatik Islak Akciger adi verilmistir.Otopsi çalismalarina dayanarak ani dramatik akut solunum yetmezligine eslik eden patolojik durum konjestif atelektazi olarak adlandirilmistir. Vietnam savasi sirasinda çogu vaka bu sehirde tedavi edildigi için Da Nang akc olarak adlandirilmis.ARDS I. Dünya savasi srasinda savas yaralilarinda ani kollaps ve solunumsal ölüme yol açan dramatik olarak progressif klinik katastrof olarak ortaya çikmistir.Daha sonra her tip travmaya bagli olarak gelisen pulmoner ödeme yol açan akciger hasarina Travmatik Islak Akciger adi verilmistir.Otopsi çalismalarina dayanarak ani dramatik akut solunum yetmezligine eslik eden patolojik durum konjestif atelektazi olarak adlandirilmistir. Vietnam savasi sirasinda çogu vaka bu sehirde tedavi edildigi için Da Nang akc olarak adlandirilmis.

4. Tarihçe Hizla gelisen akut solunum yetmezligi (12 hasta); Dispne, takipne Hipoksemi Bilateral diffüz infiltratlar Toraks-akciger kompliansinda azalma Ölenlerin otopsisinde; alveollerde kollaps, hücresel debris ve hyalen membranlar konjesyonlu akcigerler surfaktan anormalligi Ashbaugh DH, Petty T. Lancet 1967; 2:319-32. Bildigimiz anlamda ARDS ilk kez Lancet’te Denver Gruptan 1967 de Ashbaugh ve Tomas Petty tarafindan adult: eriskin solunum sikintisi olatak tanimlanmistir. Bu otörler makalelerinde 12 hastada takipne, dispne, refrakter hipoksemi, diffüz bilateral infiltratlar ve toraks-akc kompliansinda azalma ile karakterli ve hizla gelisen akut solunum yetmezligini tanimlamislardir..Bildigimiz anlamda ARDS ilk kez Lancet’te Denver Gruptan 1967 de Ashbaugh ve Tomas Petty tarafindan adult: eriskin solunum sikintisi olatak tanimlanmistir. Bu otörler makalelerinde 12 hastada takipne, dispne, refrakter hipoksemi, diffüz bilateral infiltratlar ve toraks-akc kompliansinda azalma ile karakterli ve hizla gelisen akut solunum yetmezligini tanimlamislardir..

5. ARDS tanimi Akut baslangiç Radyografide bilateral infiltrasyon PaO2 / FiO2 < 300 ise ALI PaO2 / FiO2 < 200 ise ARDS PAOB < 18 mmHg veya sol atriyum hipertansiyonuna ait bulgu olmamasi

6. ARDS – Risk faktörleri Sik nedenler Pnömoni Mide içerigi aspirasyonu Seyrek nedenler Pulmoner kontüzyon Yag embolisi Suda bogulma Duman inhalasyonu Reperfüzyon akciger ödemi (Akciger transplanti sonrasi veya pulmoner embolektomi sonrasi)

7. Sik nedenler Sepsis Agir travma Sok Masif transfüzyon Seyrek nedenler KPB Ilaç intoksikasyonu Akut pankreatit Kan ürünleri transfüzyonu ARDS – Risk faktörleri

8. 4 merkez, 1 yillik 24 saatten fazla yasayan ARDS olgulari (n = 217) 1) Sepsis - % 44 2) Sok - %15 3) Travma - %11 (% 6 toraks disi - % 5 toraks travmasi) 4) Gastrik aspirasyon - %10 5) Diger - %34 Estenssoro E. CCM 2002;30:2450-56

9. PULMONER (PRIMER) ARDS - Direkt hasar Alveol epitel hasari ? alveoler makrofaj ve inflamatuar agin aktivasyonu ? intrapulmoner inflamasyon ? ‘Pulmoner konsolidasyon’ Pulmoner konsolidasyon: Alveol ödem, fibrin, kollajen ve nötrofil agregatlari ile dolu

10. EKSTRAPULMONER (SEKONDER) ARDS - Indirekt hasar Sistemik dolasim ? vasküler endotel hücresi ? vasküler geçirgenlik ? mikrovasküler konjesyon, interstisyel ödem Alveol içi rölatif olarak korunur

11. Patofizyoloji Akut – Eksüdatif Faz (1 – 7 gün) Fibroproliferatif Faz (7 – 21 gün) Rezolüsyon Fazi (6 – 12 ay)

12. Akut fazda (sag taraf) hem bronsiyal hem de alveoler epitel hücrelerinde sisme, çiplak kalmis bazal membran üzerinde proteinden zengin hyalen membran formasyonu. Nötrofiller hasarli kapiller endotele yapismis, önce intertisyuma oradan da alveole geçiyorlar. Alveol proteinden zengin ödem sivisi ile dolu. Alveol içinde alveoler makrofaj sitokinleri salgiliyor, bu da kemotaksis ve nötrofil aktivasyonu olusturuyor. IL-1 fibroblastlar tarafindan ekstrasellüler matrix üretimini stimüle ediyor. Nötrofiller oksidanlar, proteazlar, lökotrienler ve PAF gibi diger proinflamatuar molekülleri salgiliyor. Alveol sivisi içinde IL-1ra, soluble TNF receptör, IL-8’e karsi otoantikorlar, IL-10 ve IL-11 gibi antiinflamatuar sitokinler de mevcut. Proteinden zengin sivinin alveol içinde olmasi surfaktan inaktivasyonuna neden oluyor. MIF: makrofaj inhibitör faktör.Akut fazda (sag taraf) hem bronsiyal hem de alveoler epitel hücrelerinde sisme, çiplak kalmis bazal membran üzerinde proteinden zengin hyalen membran formasyonu. Nötrofiller hasarli kapiller endotele yapismis, önce intertisyuma oradan da alveole geçiyorlar. Alveol proteinden zengin ödem sivisi ile dolu. Alveol içinde alveoler makrofaj sitokinleri salgiliyor, bu da kemotaksis ve nötrofil aktivasyonu olusturuyor. IL-1 fibroblastlar tarafindan ekstrasellüler matrix üretimini stimüle ediyor. Nötrofiller oksidanlar, proteazlar, lökotrienler ve PAF gibi diger proinflamatuar molekülleri salgiliyor. Alveol sivisi içinde IL-1ra, soluble TNF receptör, IL-8’e karsi otoantikorlar, IL-10 ve IL-11 gibi antiinflamatuar sitokinler de mevcut. Proteinden zengin sivinin alveol içinde olmasi surfaktan inaktivasyonuna neden oluyor. MIF: makrofaj inhibitör faktör.

13. Akut – Eksüdatif Faz Hizli baslangiçli solunum yetmezligi Refrakter hipoksemi Radyolojik olarak kardiyojenik akciger ödeminden ayirt edilemez. Bilateral infiltrasyonlar yama seklinde veya asimetriktir. Pulmoner effüzyon eslik edebilir. Inflamasyon tüm akcigerde yaygin

14. Subakut- Fibroproliferatif Faz (~7-21 gün) Interstisiyal fibroblast reaksiyonu Debris ve fibrinle dolu alveoller Eksüdanin organizasyonu Lüminal organize fibrozis Kronik inflamasyon Parankimal nekroz Tip 2 pnömosit hiperplazisi Kapillerlerde azalma Intralüminal tromboz, tikayici endarterit Makrotrombüs Persistan hipoksemi Hiperkapni gelismesi Fibrozis ve alveolit Pulmoner kompliansin biraz daha azalmasi Pulmoner hipertansiyon, sag kalp yetmezligi Grafide lineer opasiteler BT’de diffüz interstisyel opasiteler ve büller Matthay MM (ed). In: Lung Biology in Health and Disease. Acute respiratory distress syndrome. Marcel Dekker, Inc. 2003, pp 75

15. Alveolun sol tarafinda, tip II hücrelerin proliferasyonu ve diferansiasyonu sonucu alveoler epitel yeniden olusuyor. Alveoler ödem sivisinin resorbsiyonu altta görülüyor, sodyum ve klor apikal membran tip II hücreleri tarafindan transport ediliyor. Sodyum epitelyal sodyum kanallari tarafindan aliniyor, tip II hücrenin içinden geçerek membrandaki Na+/K+–ATPase pompasi tarafindan disari atiliyor. Klor transportunun mekanizmasi tam olarak bilinmiyor. Su tip I hücrelerin üzerinde yeralan aquaporinler tarafindan atiliyor. Eriyebilen proteinler muhtemelen primer olarak parasellüler difüzyon, sekonder olarak alveoler epitel hücrelerin endositozu ile temizleniyor. Makrofajlar fagositoz ile erimeyen proteinleri ve apopitotik nötrofilleri uzaklastiriyor. Alveolun sag tarafinda intraalveoler ve intertisiyel granülasyon dokusunun yavas yavas yeniden modelizasyonu ve rezolüsyonu, ayrica fibrozis görülüyor.Alveolun sol tarafinda, tip II hücrelerin proliferasyonu ve diferansiasyonu sonucu alveoler epitel yeniden olusuyor. Alveoler ödem sivisinin resorbsiyonu altta görülüyor, sodyum ve klor apikal membran tip II hücreleri tarafindan transport ediliyor. Sodyum epitelyal sodyum kanallari tarafindan aliniyor, tip II hücrenin içinden geçerek membrandaki Na+/K+–ATPase pompasi tarafindan disari atiliyor. Klor transportunun mekanizmasi tam olarak bilinmiyor. Su tip I hücrelerin üzerinde yeralan aquaporinler tarafindan atiliyor. Eriyebilen proteinler muhtemelen primer olarak parasellüler difüzyon, sekonder olarak alveoler epitel hücrelerin endositozu ile temizleniyor. Makrofajlar fagositoz ile erimeyen proteinleri ve apopitotik nötrofilleri uzaklastiriyor. Alveolun sag tarafinda intraalveoler ve intertisiyel granülasyon dokusunun yavas yavas yeniden modelizasyonu ve rezolüsyonu, ayrica fibrozis görülüyor.

16. Rezolüsyon Fazi Hipoksemide giderek düzelme Pulmoner komplians’da iyilesme Radyografik bulgularda düzelme

17. ALI / ARDS Yillik insidans (ALI) = 20 – 50 / 100.000 Yillik insidans (ARDS) = 15 – 30 / 100.000 Mortalite = % 26 – 74 Mortalite çogunlukla sepsis ve diger organ yetmezliklerine bagli Vincent JL. CCM 2003; 31: S296-99 Rubenfeld GD. CCM 2003; 31: S279-84 Frutos-Vivar F. Curr Opin Crit Care 2004; 10: 1-6 MacCallum NS. Curr Opin Crit Care 2005; 11: 43-9 Acute respiratory distress syndrome and ALI are clinical syndromes characterized by inflammatory pulmonary oedema, severe hypoxaemia, reduced lung compliance and diffuse endothelial and epithelial lung injury (Ashbaugh et al., 1967; Ware & Matthay, 2000). The criteria for ALI are an acute onset, a P/F ratio (PaO2/FiO2) < 300 mmHg (40 kPa), bilateral pulmonary infiltrates on a chest X-ray and a pulmonary wedge pressure 618 mmHg if known or no clinical signs of increased left atrial pressures. For ARDS the criteria are the same except for the P/F ratio which is <200 mmHg (26Æ7 kPa) (Bernard et al., 1994).Acute respiratory distress syndrome and ALI are clinical syndromes characterized by inflammatory pulmonary oedema, severe hypoxaemia, reduced lung compliance and diffuse endothelial and epithelial lung injury (Ashbaugh et al., 1967; Ware & Matthay, 2000). The criteria for ALI are an acute onset, a P/F ratio (PaO2/FiO2) < 300 mmHg (40 kPa), bilateral pulmonary infiltrates on a chest X-ray and a pulmonary wedge pressure 618 mmHg if known or no clinical signs of increased left atrial pressures. For ARDS the criteria are the same except for the P/F ratio which is <200 mmHg (26Æ7 kPa) (Bernard et al., 1994).

19. Perhaps the most important advance in ALI and ARDS research has been the recognition that mechanical ventilation, although necessary to preserve life, can potentiate or directly injure the lungs through a variety of mechanisms collectively referred to as ventilator associated lung injury.14-16 These mechanisms include exposure to high inflation pressures or overdistention (barotrauma or volutrauma),17 repetitive opening and closing of alveoli (atelectrauma), 18 and mechanotransduction resulting in up-regulated cytokine release and a systemic inflammatory response (biotrauma).19 Perhaps the most important advance in ALI and ARDS research has been the recognition that mechanical ventilation, although necessary to preserve life, can potentiate or directly injure the lungs through a variety of mechanisms collectively referred to as ventilator associated lung injury.14-16 These mechanisms include exposure to high inflation pressures or overdistention (barotrauma or volutrauma),17 repetitive opening and closing of alveoli (atelectrauma), 18 and mechanotransduction resulting in up-regulated cytokine release and a systemic inflammatory response (biotrauma).19

20. Figure 1. Normal Rat Lungs and Rat Lungs after Receiving High-Pressure Mechanical Ventilation at a Peak Airway Pressure of 45 cm of Water After 5 minutes of ventilation, focal zones of atelectasis were evident, in particular at the left lung apex. After 20 minutes of ventilation, the lungs were markedly enlarged and congested; edema fluid filled the tracheal cannula. Adapted from Dreyfuss et al.8 with the permission of the publisher. Mekanik ventilasyon öncesinde akciger hasari ne kadar fazla ise olusan hasar o kadar fazla olur Figure 1. Normal Rat Lungs and Rat Lungs after Receiving High-Pressure Mechanical Ventilation at a Peak Airway Pressure of 45 cm of Water After 5 minutes of ventilation, focal zones of atelectasis were evident, in particular at the left lung apex. After 20 minutes of ventilation, the lungs were markedly enlarged and congested; edema fluid filled the tracheal cannula. Adapted from Dreyfuss et al.8 with the permission of the publisher. Mekanik ventilasyon öncesinde akciger hasari ne kadar fazla ise olusan hasar o kadar fazla olur

21. A, The chest radiograph shows bilateral pulmonary infiltrates that appear to be diffuse. B, A computed tomographic scan of the thorax from the same patient demonstrates that the distribution of the bilateral infiltrates is predominantly in dependent regions with more normal-appearing lung in nondependent regions. Fig. 1 Anteroposterior chest radiography (right) and CT— apex, hilum, and base—(left) in ARDS from sepsis, taken at 5 cmH2O end-expiratory pressure. Chest radiography shows diffuse ground glass opacification, sparing the right upper lung. CT shows inhomogeneous disease and both the craniocaudal and sternovertebral gradients. (From Gattinoni et al. [20]) A, The chest radiograph shows bilateral pulmonary infiltrates that appear to be diffuse. B, A computed tomographic scan of the thorax from the same patient demonstrates that the distribution of the bilateral infiltrates is predominantly in dependent regions with more normal-appearing lung in nondependent regions. Fig. 1 Anteroposterior chest radiography (right) and CT— apex, hilum, and base—(left) in ARDS from sepsis, taken at 5 cmH2O end-expiratory pressure. Chest radiography shows diffuse ground glass opacification, sparing the right upper lung. CT shows inhomogeneous disease and both the craniocaudal and sternovertebral gradients. (From Gattinoni et al. [20])

22. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990;16:372–377 Yeni Zelanda’da In the 1990s Hickling et al. [46] introduced low VT ventilation to “rest the lung.” This technique, referred to as “permissive hypercapnia,” to underline the price paid for resting the lung, had been used with success in asthma patients [47]. In our opinion, however, the real “revolution” was not the use of low tidal volume but the change of the goal. For nearly 20 years this had been normal gas exchange, but from the 1990s the accepted target became gentle lung treatment while maintaining adequate oxygenation and accepting high PCO2 [48]. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a "lung injury score" greater than or equal to 2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%, chi 2 = 11.64, p less than 0.001). Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure. As a consequence, in recent years there has been a shift in the goal of mechanical ventilation in ALI/ARDS patients from maintaining a normal gas exchange to protection of the lung against ventilation-induced lung injury (VILI) by protective ventilatory strategies (Fan et al., 2005). Yeni Zelanda’da In the 1990s Hickling et al. [46] introduced low VT ventilation to “rest the lung.” This technique, referred to as “permissive hypercapnia,” to underline the price paid for resting the lung, had been used with success in asthma patients [47]. In our opinion, however, the real “revolution” was not the use of low tidal volume but the change of the goal. For nearly 20 years this had been normal gas exchange, but from the 1990s the accepted target became gentle lung treatment while maintaining adequate oxygenation and accepting high PCO2 [48]. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a "lung injury score" greater than or equal to 2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%, chi 2 = 11.64, p less than 0.001). Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure. As a consequence, in recent years there has been a shift in the goal of mechanical ventilation in ALI/ARDS patients from maintaining a normal gas exchange to protection of the lung against ventilation-induced lung injury (VILI) by protective ventilatory strategies (Fan et al., 2005).

23. Dreyfuss D, Saumon G. Should the lung be rested or recruited? The Charybdis and Scylla of ventilator management. AJRCCM 1994;149: 1066-67 Scylla (Sila) ve Charybdis (Karibdis) terimi bir kimsenin iki tehlike arasinda kaldigini ve birisinden uzaklastiginda digerine yaklastigini ifade etmektedir. Italya-Sicilya arasindaki Messina Bogazi veya son zamanlarda kuzeybati Yunanistan’da Skilla burnu oldugu iddaa edilmis. Asil’in annesi olan Tetis’in (su tanriçasi olarak bilinmektedir) Argo gemisiyle Jason’a eslik eden kahramanlar olan Argonatlar’a yol gösterdigi ve onlari bu bogazdan kurtardigi mitolojide söylenir. As has been described before, intensivists wishing to oxygenate and ventilate patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have become the argonauts of modern intensive care medicine (Dreyfuss & Saumon, 1994). They have to navigate between the danger of overdistension of relatively healthy non-dependent lung regions and repeated alveolar collapse and re- expansion of basal consolidated lung regions (Froese, 1997). With this article, we hope to be of some help like Thetis was for Jason. Scylla (Sila) ve Charybdis (Karibdis) terimi bir kimsenin iki tehlike arasinda kaldigini ve birisinden uzaklastiginda digerine yaklastigini ifade etmektedir. Italya-Sicilya arasindaki Messina Bogazi veya son zamanlarda kuzeybati Yunanistan’da Skilla burnu oldugu iddaa edilmis. Asil’in annesi olan Tetis’in (su tanriçasi olarak bilinmektedir) Argo gemisiyle Jason’a eslik eden kahramanlar olan Argonatlar’a yol gösterdigi ve onlari bu bogazdan kurtardigi mitolojide söylenir. As has been described before, intensivists wishing to oxygenate and ventilate patients with adult respiratory distress syndrome (ARDS) and acute lung injury (ALI) have become the argonauts of modern intensive care medicine (Dreyfuss & Saumon, 1994). They have to navigate between the danger of overdistension of relatively healthy non-dependent lung regions and repeated alveolar collapse and re- expansion of basal consolidated lung regions (Froese, 1997). With this article, we hope to be of some help like Thetis was for Jason.

24. Mekanik ventilasyonun bu istenmeyen etkilerini ortadan kaldirmak için akciger koruyucu ventilasyon teknikleri uygulanmasidir. Bu teknigin temel özellikleri küçük tidal volüm veya basinçlarin uygulanmasi, kapali alveollerin açilmasi ve açilan alveollerin yeniden kapanmasinin önlenmesidir. Mekanik ventilasyonun bu istenmeyen etkilerini ortadan kaldirmak için akciger koruyucu ventilasyon teknikleri uygulanmasidir. Bu teknigin temel özellikleri küçük tidal volüm veya basinçlarin uygulanmasi, kapali alveollerin açilmasi ve açilan alveollerin yeniden kapanmasinin önlenmesidir.

25. DÜSÜK TIDAL VOLÜM DÜSÜK BASINÇ

26. Figure 2. Conventional Ventilation as Compared with Protective Ventilation This example of ventilation of a 70-kg patient with ARDS shows that conventional ventilation at a tidal volume of 12 ml per kilogram of body weight and an end- xpiratory pressure of 0 cm of water (Panel A) can lead to alveolar overdistention (at peak inflation) and collapse (at the end of exhalation). Protective ventilation at a tidal volume of 6 ml per kilogram (Panel B) limits overinflation and end-expiratory collapse by providing a low tidal volume and an adequate positive end- expiratory pressure. Adapted from Tobin.18 Conv V = 12 ml/kg, düsük PEEP, PaCO2 = 35-38 LPV = 6 ml/kg, yüksek PEEP (+ 2 cmH2O LIP), permisif hiperkapniFigure 2. Conventional Ventilation as Compared with Protective Ventilation This example of ventilation of a 70-kg patient with ARDS shows that conventional ventilation at a tidal volume of 12 ml per kilogram of body weight and an end- xpiratory pressure of 0 cm of water (Panel A) can lead to alveolar overdistention (at peak inflation) and collapse (at the end of exhalation). Protective ventilation at a tidal volume of 6 ml per kilogram (Panel B) limits overinflation and end-expiratory collapse by providing a low tidal volume and an adequate positive end- expiratory pressure. Adapted from Tobin.18 Conv V = 12 ml/kg, düsük PEEP, PaCO2 = 35-38 LPV = 6 ml/kg, yüksek PEEP (+ 2 cmH2O LIP), permisif hiperkapni

27. Ilk üçü 1998, Brower 1999 yilinda Amato LIP = Pflex + 2 cmH20 PEEP uygulamis. Amato, Kontrol grubundaki yüksek mortalite nedeniyle elestirilmis. Ancak hastalar agir hastalarmis (ort. Organ yetmezligi sayisi = 3.6 / hasta) All four studies had limited statistical power due to small sample sizes, and the differences in tidal volume between treatment groups achieved in the three negative trials were notably smaller than that in the one positive trial, Ilk üçü 1998, Brower 1999 yilinda Amato LIP = Pflex + 2 cmH20 PEEP uygulamis. Amato, Kontrol grubundaki yüksek mortalite nedeniyle elestirilmis. Ancak hastalar agir hastalarmis (ort. Organ yetmezligi sayisi = 3.6 / hasta) All four studies had limited statistical power due to small sample sizes, and the differences in tidal volume between treatment groups achieved in the three negative trials were notably smaller than that in the one positive trial,

28. Istatistiksel gücü yüksek Yaklasik % 9 absolü REDUCTION in death.Istatistiksel gücü yüksek Yaklasik % 9 absolü REDUCTION in death.

29. Hesaplanan Vücut Agirligi (Predicted Body Weight) HVA (erkek) = 50.0 + 0.91 (Boy(cm) – 152.4) HVA (kadin) = 45.5 + 0.91 (Boy(cm) – 152.4) The concept underlying this approach is that it normalizes the tidal volume to lung size, since lung size has been shown to depend most strongly on height and sex. For example, a person who ideally weighs 70 kg and who then gains 35 kg has essentially the same lung size as he or she did when at a weight of 70 kg and should not receive ventilation with a higher tidal volume just because of the weight gain. PBW kullanilmazsa özellikle kadinlarda ve boyu kisa olanlarda gereksiz yüksek hacimlerin uygulanmasi söz konusu.The concept underlying this approach is that it normalizes the tidal volume to lung size, since lung size has been shown to depend most strongly on height and sex. For example, a person who ideally weighs 70 kg and who then gains 35 kg has essentially the same lung size as he or she did when at a weight of 70 kg and should not receive ventilation with a higher tidal volume just because of the weight gain. PBW kullanilmazsa özellikle kadinlarda ve boyu kisa olanlarda gereksiz yüksek hacimlerin uygulanmasi söz konusu.

30. The pooled estimate of treatment effect of in ALI/ARDS favours protective ventilation, but it failed to achieve statistical significance on random effects estimation. Early stopping in four of the five trials considered may have been a factor contributing to heterogeneity. In ALI and ARDS mechanical ventilation with low tidal volumes is not detrimental and may have advantage below threshold levels of 7.7 ml/kg-predicted. Further trials, with standardised prescription of ventilatory parameters, appear to be necessary to define optimal mechanical ventilation in ALI/ARDS. The pooled estimate of treatment effect of in ALI/ARDS favours protective ventilation, but it failed to achieve statistical significance on random effects estimation. Early stopping in four of the five trials considered may have been a factor contributing to heterogeneity. In ALI and ARDS mechanical ventilation with low tidal volumes is not detrimental and may have advantage below threshold levels of 7.7 ml/kg-predicted. Further trials, with standardised prescription of ventilatory parameters, appear to be necessary to define optimal mechanical ventilation in ALI/ARDS.

31. 2004 yilindaki metaanalizlerini güncellemislerdir. Daha önceki 5 arastirmaya 2006 yilinda Villar’in yaptigi arastirmayi eklemislerdir. All of the included studies were multi-centre ones trials. The European study (Brochard 1998) was unique in the inclusion of patients with single organ failure (lung injury) only. Time that had elapsed from eligibility to randomization ranged from one hour to 36 hours. In one study (Villar 2006), only patients who demonstrated persistent ARDS 24 hours after initially meeting ARDS criteria, were enrolled. TheAPACHE II score at baseline was in the range of 17±8 SD (Brochard 1998) to 28±7 SD (Amato 1998). Two trials used the APACHE III score (ARDS Network 2000; Brower 1999). The APACHE III score ranged from 81±28 SD (ARDS Network 2000) to 90±26 SD (Brower 1999). The severity of impairment of lung function was reported according to partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (PaO2:FiO2). Delivery of interventions for each trial varied. Five trials (ARDS Network 2000; Brochard 1998; Brower 1999; Stewart 1998; Villar 2006) set the tidal volume based on body weight, without the use of a Pressure-Volume (PV) curve. However, in the ARDS Network, Brower, Stewart and Villar trials, the tidal volume was set according to predicted (or ideal) body weight (IBW), which was calculated according to the gender and height of the patient. IBW is, on average, 20% less than measured body weight. When transformed to ml/kg measured body weight, the mean tidal volume in the ARDS Network trial ranged from 9.4 to 9.9 ml/kg in the control group, which was quite similar to values used in the other trials, and 5.2 ml/kg in the low tidal volume group, which was lower than other trials. Two trials (Amato 1998; Villar 2006) compared the effect of a combined strategy composed of a low tidal volume and relatively high PEEP titrated according to the PV curve. Amato added an intermittent recruitment manoeuvre, and used in the control group a ventilatory strategy aimed at normalizing partial pressure of carbon dioxide, without limitation in peak inspiratory pressure. Limits of airway plateau pressure ranged from 22 to 30 cm H2O in the protective arms, and from 31 to 37 cm H2O in the conventional arms. Most studies focused on plateau airway pressure, whereas one study focused on peak inspiratory airway pressure (Brochard 1998). Protocols for the management of acidosis using bicarbonate infusions were developed in all trials, although there were some differences. ARDS Network investigators (ARDS Network 2000) were most aggressive in attempting to keep pH greater than 7.30 for all patients and allowed violations of the tidal volume and airway pressure limits when pH fell below 7.15. In contrast, another study (Stewart 1998) did not dictate volume and pressure violations until pH fell to 7.00. 2004 yilindaki metaanalizlerini güncellemislerdir. Daha önceki 5 arastirmaya 2006 yilinda Villar’in yaptigi arastirmayi eklemislerdir. All of the included studies were multi-centre ones trials. The European study (Brochard 1998) was unique in the inclusion of patients with single organ failure (lung injury) only. Time that had elapsed from eligibility to randomization ranged from one hour to 36 hours. In one study (Villar 2006), only patients who demonstrated persistent ARDS 24 hours after initially meeting ARDS criteria, were enrolled. TheAPACHE II score at baseline was in the range of 17±8 SD (Brochard 1998) to 28±7 SD (Amato 1998). Two trials used the APACHE III score (ARDS Network 2000; Brower 1999). The APACHE III score ranged from 81±28 SD (ARDS Network 2000) to 90±26 SD (Brower 1999). The severity of impairment of lung function was reported according to partial pressure of arterial oxygen to the fraction of inspired oxygen ratio (PaO2:FiO2). Delivery of interventions for each trial varied. Five trials (ARDS Network 2000; Brochard 1998; Brower 1999; Stewart 1998; Villar 2006) set the tidal volume based on body weight, without the use of a Pressure-Volume (PV) curve. However, in the ARDS Network, Brower, Stewart and Villar trials, the tidal volume was set according to predicted (or ideal) body weight (IBW), which was calculated according to the gender and height of the patient. IBW is, on average, 20% less than measured body weight. When transformed to ml/kg measured body weight, the mean tidal volume in the ARDS Network trial ranged from 9.4 to 9.9 ml/kg in the control group, which was quite similar to values used in the other trials, and 5.2 ml/kg in the low tidal volume group, which was lower than other trials. Two trials (Amato 1998; Villar 2006) compared the effect of a combined strategy composed of a low tidal volume and relatively high PEEP titrated according to the PV curve. Amato added an intermittent recruitment manoeuvre, and used in the control group a ventilatory strategy aimed at normalizing partial pressure of carbon dioxide, without limitation in peak inspiratory pressure. Limits of airway plateau pressure ranged from 22 to 30 cm H2O in the protective arms, and from 31 to 37 cm H2O in the conventional arms. Most studies focused on plateau airway pressure, whereas one study focused on peak inspiratory airway pressure (Brochard 1998). Protocols for the management of acidosis using bicarbonate infusions were developed in all trials, although there were some differences. ARDS Network investigators (ARDS Network 2000) were most aggressive in attempting to keep pH greater than 7.30 for all patients and allowed violations of the tidal volume and airway pressure limits when pH fell below 7.15. In contrast, another study (Stewart 1998) did not dictate volume and pressure violations until pH fell to 7.00.

32. Mortality was measured at a cut-off point of day 60 in one study (Brochard1998), day 180 in one study (ARDS Network 2000) and at hospital discharge in two studies (Brower 1999;Stewart 1998). In one study (Amato 1998), both mortality at day 28 and at hospital discharge were reported. ICU and hospital mortality were reported in one study (Villar 2006). Importantly, in ARDS Network 2000 patients were followed until discharged home or for 180 days, whichever occurred first. only three trials reported duration of mechanical ventilation (Brochard 1998; Brower 1999; Stewart 1998) (see Additional Table 07). In the ARDS Network study, this outcome was reported as median number of days, without further description. However, the absence of a strict protocol for weaning in all the trials, apart from the ARDS Network study (ARDS Network 2000), makes this outcome, although important for clinical and economic implications, difficult to evaluate objectively. In five studies (Amato 1998; ARDS Network 2000 ;Brochard 1998; Brower 1999; Villar 2006) sample size was calculated before the beginning of the study. With the exception of the Amato trial, which reached the target sample (53 patients), the other four studies were stopped early. We found evidence that ventilation strategy using a tidal volume equal or less than 7 ml/kg of measured body weight and plateau pressure less than 31 mm H2O reduced mortality at day 28. Evidence from a new study (Villar 2006) shows that it also reduces hospital mortality. The experimental intervention included permissive hypercapnia, variable levels of PEEP and low plateau airway pressure. The traditional intervention consisted of higher tidal volume, normocapnia, lower levels of PEEP and potentially higher plateau pressures. Therefore, the studies performed a comparison of two approaches rather than two single interventions, and caution is required in interpreting these results, especially when analyses have been inspired by looking at the available aggregate data, which makes it difficult to assess the respective importance of each factor. The benefit from low tidal volume ventilation was maintained, although reduced, when considering hospital mortality as the endpoint. Mortality was measured at a cut-off point of day 60 in one study (Brochard1998), day 180 in one study (ARDS Network 2000) and at hospital discharge in two studies (Brower 1999;Stewart 1998). In one study (Amato 1998), both mortality at day 28 and at hospital discharge were reported. ICU and hospital mortality were reported in one study (Villar 2006). Importantly, in ARDS Network 2000 patients were followed until discharged home or for 180 days, whichever occurred first. only three trials reported duration of mechanical ventilation (Brochard 1998; Brower 1999; Stewart 1998) (see Additional Table 07). In the ARDS Network study, this outcome was reported as median number of days, without further description. However, the absence of a strict protocol for weaning in all the trials, apart from the ARDS Network study (ARDS Network 2000), makes this outcome, although important for clinical and economic implications, difficult to evaluate objectively. In five studies (Amato 1998; ARDS Network 2000 ;Brochard 1998; Brower 1999; Villar 2006) sample size was calculated before the beginning of the study. With the exception of the Amato trial, which reached the target sample (53 patients), the other four studies were stopped early. We found evidence that ventilation strategy using a tidal volume equal or less than 7 ml/kg of measured body weight and plateau pressure less than 31 mm H2O reduced mortality at day 28. Evidence from a new study (Villar 2006) shows that it also reduces hospital mortality. The experimental intervention included permissive hypercapnia, variable levels of PEEP and low plateau airway pressure. The traditional intervention consisted of higher tidal volume, normocapnia, lower levels of PEEP and potentially higher plateau pressures. Therefore, the studies performed a comparison of two approaches rather than two single interventions, and caution is required in interpreting these results, especially when analyses have been inspired by looking at the available aggregate data, which makes it difficult to assess the respective importance of each factor. The benefit from low tidal volume ventilation was maintained, although reduced, when considering hospital mortality as the endpoint.

33. DÜSÜK TIDAL VOLÜM PRATIKTE UYGULANIYOR MU? Koruyucu ventilasyon stratejileri yaygin uygulanmamaktadir Weinert CR. Am J Respir Crit Care Med 2003; 167:1304–1309 ARDS Net çalismasindan sonra ALI/ARDS hastalarina uygulanan ortalama VT 11.7 mL/kg’dan 10.7 mL/kg’a düsmüstür Young MP. Crit Care Med 2004; 32:1260–1265 Kontraendikasyon mevcut olan hastalar dislandiktan sonra da benzer Kalhan R. Crit Care Med 2006; 34:300–306 Hasta uyumsuzlugu, takipne, hiperkapni, asidoz Rubenfeld GD. Crit Care Med 2004; 32: 1289-93 Failure to effectively implement evidence into clinical practice is one of the most important challenges in medicine. 1 Mechanical ventilation with a lung-protective ventilation (LPV) strategy for patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is no exception. However, despite that evidence, subsequent studies found that the proportion of patients who received LPV remained modest.5–8 We previously found that physicians were compliant with LPV in a minority of patients, even after excluding patients for whom LPV was contraindicated at the onset of ALI.9 One may posit various reasons for this slow adoption among physicians, but few are supported by recent evidence. For example, some practitioners may choose to control plateau pressures instead of tidal volumes, despite the clear benefit of using 6 mL/kg tidal volume at every plateau pressure. However, the data gathered by Young et al. (4) indicate that the plateau pressures have also not changed since ARMA. Failure to effectively implement evidence into clinical practice is one of the most important challenges in medicine. 1 Mechanical ventilation with a lung-protective ventilation (LPV) strategy for patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is no exception. However, despite that evidence, subsequent studies found that the proportion of patients who received LPV remained modest.5–8 We previously found that physicians were compliant with LPV in a minority of patients, even after excluding patients for whom LPV was contraindicated at the onset of ALI.9 One may posit various reasons for this slow adoption among physicians, but few are supported by recent evidence. For example, some practitioners may choose to control plateau pressures instead of tidal volumes, despite the clear benefit of using 6 mL/kg tidal volume at every plateau pressure. However, the data gathered by Young et al. (4) indicate that the plateau pressures have also not changed since ARMA.

35. Hiperkapni Pulmoner HT, katekolamin salinimina bagli proaritmik etki, serebral vazodilatasyon Ilimli hiperkapni ARDS’de çogunlukla iyi tolere edilir Laffey JG. Intensive Care Med 2004; 30: 347-56 Potansiyel olarak hemodinamik açidan yararli olabilir ? Kavanagh BP. Minerva Anestesiol 2006; 72: 567-76 KIBAS varliginda kaçinilmalidir Lowe GJ. Curr Opin Crit Care 2006; 12: 3–7 Lowe GJ. Curr Opin Crit Care 12:3–7. 2006 In some cases, however, it can be challenging to maintain a normal PaCO2 while avoiding overdistension injury. The first step we recommend in these cases (regardless of whether the patient is brain injured) is a careful evaluation of the patient to look for factors that could improve CO2 clearance – these include removing any excess deadspace from the ventilator circuit, ensuring adequate patient–ventilator synchrony, checking the endotracheal tube for partial obstruction, and considering manoeuvres to improve respiratory system compliance such as draining large pleural effusions or massive ascites. If a high PaCO2 remains a problem after these steps then one must carefully weigh up the risks and benefits of targeting eucapnia versus a limited tidal volume. As stated above, there is no direct clinical evidence to guide these decisions. Our practice is to first clarify whether brain-injured patients truly have ALI/ARDS, or whether they were receiving lower tidal volumes in a prophylactic fashion [42]. If the latter is the case, we typically let tidal volumes rise to ensure a normal PaCO2. If they truly have ALI/ARDS we next consider whether the patient has a raised ICP, by clinical examination and by direct measurement. If ICP is not high and the patient does have ALI we would usually continue to target a low tidal volume, allowing the PaCO2 to rise slightly. We continue to monitor the ICP and clinical status of the patient closely, but if these are stable we might allow the PaCO2 to sit in the 45– 55 mmHg range. From this point the PaCO2 could still be acutely corrected back down to normal with hyperventilation if a neurological clinical deterioration were to develop. Finally, in patients with ALI/ARDS who have raised ICP or are requiring active management such as mannitol to control their ICP, we avoid hypercapnia, even if this means allowing tidal volumes to rise. Overall, it appears that when PEEP is set at levels that are lower than ICP, it does not have a subsequent significant effect on ICP [49]. 49 Andrews PJ. Pressure, flow and Occam’s razor: a matter of ‘steal’? Intensive Care Med 2005; 31:323–324. Lowe GJ. Curr Opin Crit Care 12:3–7. 2006 In some cases, however, it can be challenging to maintain a normal PaCO2 while avoiding overdistension injury. The first step we recommend in these cases (regardless of whether the patient is brain injured) is a careful evaluation of the patient to look for factors that could improve CO2 clearance – these include removing any excess deadspace from the ventilator circuit, ensuring adequate patient–ventilator synchrony, checking the endotracheal tube for partial obstruction, and considering manoeuvres to improve respiratory system compliance such as draining large pleural effusions or massive ascites. If a high PaCO2 remains a problem after these steps then one must carefully weigh up the risks and benefits of targeting eucapnia versus a limited tidal volume. As stated above, there is no direct clinical evidence to guide these decisions. Our practice is to first clarify whether brain-injured patients truly have ALI/ARDS, or whether they were receiving lower tidal volumes in a prophylactic fashion [42]. If the latter is the case, we typically let tidal volumes rise to ensure a normal PaCO2. If they truly have ALI/ARDS we next consider whether the patient has a raised ICP, by clinical examination and by direct measurement. If ICP is not high and the patient does have ALI we would usually continue to target a low tidal volume, allowing the PaCO2 to rise slightly. We continue to monitor the ICP and clinical status of the patient closely, but if these are stable we might allow the PaCO2 to sit in the 45– 55 mmHg range. From this point the PaCO2 could still be acutely corrected back down to normal with hyperventilation if a neurological clinical deterioration were to develop. Finally, in patients with ALI/ARDS who have raised ICP or are requiring active management such as mannitol to control their ICP, we avoid hypercapnia, even if this means allowing tidal volumes to rise. Overall, it appears that when PEEP is set at levels that are lower than ICP, it does not have a subsequent significant effect on ICP [49]. 49 Andrews PJ. Pressure, flow and Occam’s razor: a matter of ‘steal’? Intensive Care Med 2005; 31:323–324.

36. ARDS Net çalismasina dahil edilen 61 hasta Increased sedation requirements are frequently cited as a reason not to implement the ARDS Network protocol. A recent controversial review of the ARDS Network study considered “higher doses of sedatives and narcotics necessary to maintain patient comfort [and] the addition of neuromuscular blockade” as possible explanations for the authors’ conclusions that the ARDS Network low tidal volume strategy may actually increase mortality (11 Eichacker). The authors of an instructional article on implementing the ARDS Network protocol wrote that “high levels of sedation are often necessary to eliminate severe respiratory distress and patient- ventilator discoordination” in lungprotective ventilation (4 Kallet). Moreover, patients receiving a low tidal volume strategy did not receive increased days of neuromuscular blockade compared with the traditional tidal volume strategy. It is possible that the rapid shallow breathing pattern created by lower tidal volumes and higher respiratory rates simply appears uncomfortable to caregivers but is not a source of discomfort for the patient. Furthermore, other factors, such as the presence of an endotracheal tube (29), airway suctioning (30), ambient noise (31), sleep disruption (32), or procedures (33) may contribute to patient discomfort to such a degree that the mode of mechanical ventilation has a minor effect. Our results, however, are compatible with data from the entire ARDS Network study demonstrating that the number of days of sedation and neuromuscular blockade was similar in both study arms (3). Since ARDS Network patients in the higher volume arm generally had worse outcomes, including fewer organ failure free days (presumably due to less ventilator- nduced organ failure), this also supports the hypothesis that severity of illness, rather than ventilator mode, influenced sedative drug use in the study. Kidney and hepatic failure in the high tidal volume arm patients might have led clinicians to use lower doses of all medications including those evaluated in this study. Increased sedation requirements are frequently cited as a reason not to implement the ARDS Network protocol. A recent controversial review of the ARDS Network study considered “higher doses of sedatives and narcotics necessary to maintain patient comfort [and] the addition of neuromuscular blockade” as possible explanations for the authors’ conclusions that the ARDS Network low tidal volume strategy may actually increase mortality (11 Eichacker). The authors of an instructional article on implementing the ARDS Network protocol wrote that “high levels of sedation are often necessary to eliminate severe respiratory distress and patient- ventilator discoordination” in lungprotective ventilation (4 Kallet). Moreover, patients receiving a low tidal volume strategy did not receive increased days of neuromuscular blockade compared with the traditional tidal volume strategy. It is possible that the rapid shallow breathing pattern created by lower tidal volumes and higher respiratory rates simply appears uncomfortable to caregivers but is not a source of discomfort for the patient. Furthermore, other factors, such as the presence of an endotracheal tube (29), airway suctioning (30), ambient noise (31), sleep disruption (32), or procedures (33) may contribute to patient discomfort to such a degree that the mode of mechanical ventilation has a minor effect. Our results, however, are compatible with data from the entire ARDS Network study demonstrating that the number of days of sedation and neuromuscular blockade was similar in both study arms (3). Since ARDS Network patients in the higher volume arm generally had worse outcomes, including fewer organ failure free days (presumably due to less ventilator- nduced organ failure), this also supports the hypothesis that severity of illness, rather than ventilator mode, influenced sedative drug use in the study. Kidney and hepatic failure in the high tidal volume arm patients might have led clinicians to use lower doses of all medications including those evaluated in this study.

37. Daha az korunmus akcigerde inspiryum sonunda hiperinflasyon gösteren alanlar mevcut. Bunlarin daha çok Pplat 28’in üzerinde oldugunu belirlemislerDaha az korunmus akcigerde inspiryum sonunda hiperinflasyon gösteren alanlar mevcut. Bunlarin daha çok Pplat 28’in üzerinde oldugunu belirlemisler

39. KAPALI ALVEOLLERIN AÇILMASI VE KAPANMASININ ÖNLENMESI (RECRUITMENT MANEVRALARI + PEEP) Lachmann’in 1992 yilinda nitelendirdigi akcigerlerin açilmasi ve açik tutulmasi kavramindan sonra bu ikisini bir arada degerlendirmek daha dogru olacaktir. PEEP daha çok alveollerin kapanmasinin önlenmesi açisindan önemliyse de daha yüksek inspiryum sonu P’a yol açarak indirekt olarak kollabe alanlarin açilmasina katkida bulunabilir. Lachmann’in 1992 yilinda nitelendirdigi akcigerlerin açilmasi ve açik tutulmasi kavramindan sonra bu ikisini bir arada degerlendirmek daha dogru olacaktir. PEEP daha çok alveollerin kapanmasinin önlenmesi açisindan önemliyse de daha yüksek inspiryum sonu P’a yol açarak indirekt olarak kollabe alanlarin açilmasina katkida bulunabilir.

40. PEEP Hiperinflasyon

42. But neither these findings nor the significantly lower mortality rates observed in the intervention groups in the trials of both Villar et al36 and Amato et al10 could be solely attributed to higher levels of PEEP since the intervention strategies in these trials employed both low tidal volumes and high levels of PEEP. The isolated benefit to survival of low tidal volume ventilation was demonstrated in ARMA,14 as discussed previously, since patients in the intervention group were treated with levels of PEEP that were no different than those utilized in the control group. But another trial was needed to evaluate the efficacy of high PEEP in which all patients received low tidal volume ventilation. Bu iki çalismada da düsük Vt ile birlikte yüksek PEEP uygulandigindan sonuçlari yalniz yüksek PEEP’e baglamak dogru degil. But neither these findings nor the significantly lower mortality rates observed in the intervention groups in the trials of both Villar et al36 and Amato et al10 could be solely attributed to higher levels of PEEP since the intervention strategies in these trials employed both low tidal volumes and high levels of PEEP. The isolated benefit to survival of low tidal volume ventilation was demonstrated in ARMA,14 as discussed previously, since patients in the intervention group were treated with levels of PEEP that were no different than those utilized in the control group. But another trial was needed to evaluate the efficacy of high PEEP in which all patients received low tidal volume ventilation. Bu iki çalismada da düsük Vt ile birlikte yüksek PEEP uygulandigindan sonuçlari yalniz yüksek PEEP’e baglamak dogru degil.

43. In the first 80 patients randomly assigned to the higher-PEEP group, we assessed the safety and efficacy of recruitment maneuvers. One or two such maneuvers were conducted during the first four days after randomization by applying continuous positive airway pressure of 35 to 40 cm of water for 30 seconds. The subsequent mean increase in arterial oxygenation was small and transient. 22 Therefore, we discontinued recruitment maneuvers for the remainder of the trial. Ilk 171 hastadan sonra aradaki farki belirgin hale getirmek için daha yüksek PEEP düzeylerine çikilmis. In the first 80 patients randomly assigned to the higher-PEEP group, we assessed the safety and efficacy of recruitment maneuvers. One or two such maneuvers were conducted during the first four days after randomization by applying continuous positive airway pressure of 35 to 40 cm of water for 30 seconds. The subsequent mean increase in arterial oxygenation was small and transient. 22 Therefore, we discontinued recruitment maneuvers for the remainder of the trial. Ilk 171 hastadan sonra aradaki farki belirgin hale getirmek için daha yüksek PEEP düzeylerine çikilmis.

44. Although the patients treated with higher PEEP clearly experienced increases in oxygenation, as measured by the Pao2/Fio2 ratio, compared with patients treated with lower PEEP, the in-hospital mortality rate was similar in the two treatment groups (p 0.48) [Table 1]. The duration of mechanical ventilation and the duration of nonpulmonary organ failure were similar in the two groups as well. Yüskek PEEP grubundaki ilk 80 hastaya ek olarak RM uygulanmis (35 – 40 cmH2O CPAP; 30 sn süreyle). RM uygulanmayan hastalarla karsilastirildiginda oksijenasyonda yalniz düsük ve geçici yükselmelere yol açtigindan vazgeçilmis.Although the patients treated with higher PEEP clearly experienced increases in oxygenation, as measured by the Pao2/Fio2 ratio, compared with patients treated with lower PEEP, the in-hospital mortality rate was similar in the two treatment groups (p 0.48) [Table 1]. The duration of mechanical ventilation and the duration of nonpulmonary organ failure were similar in the two groups as well. Yüskek PEEP grubundaki ilk 80 hastaya ek olarak RM uygulanmis (35 – 40 cmH2O CPAP; 30 sn süreyle). RM uygulanmayan hastalarla karsilastirildiginda oksijenasyonda yalniz düsük ve geçici yükselmelere yol açtigindan vazgeçilmis.

46. PEEP improves hypoxemia and decreases intrapulmonary shunting, and these effects have been the basis for titrating PEEP in clinical practice.2 Although the mechanisms of this protective effect are not fully elucidated, they may be mediated by PEEP-induced alveolar recruitment, which avoids cyclic air- way collapse and reopening, protects lung surfactant, and improves ventilation homogeneity. Although oxygenation and alveolar recruitment are often associated, the former is influenced by many other factors, including hemodynamics, and is therefore a poor surrogate for recruitment. Analysis of the volume-pressure relationship of the respiratory system has shown that alveolar recruitment occurs all along the volume-pressure relationship and depends on the airway pressure reached.7-9 Also, a combination of small tidal volume and high PEEP was more effective than the opposite in promoting recruitment at a given maximal airway pressure. 10,11 PEEP improves hypoxemia and decreases intrapulmonary shunting, and these effects have been the basis for titrating PEEP in clinical practice.2 Although the mechanisms of this protective effect are not fully elucidated, they may be mediated by PEEP-induced alveolar recruitment, which avoids cyclic air- way collapse and reopening, protects lung surfactant, and improves ventilation homogeneity. Although oxygenation and alveolar recruitment are often associated, the former is influenced by many other factors, including hemodynamics, and is therefore a poor surrogate for recruitment. Analysis of the volume-pressure relationship of the respiratory system has shown that alveolar recruitment occurs all along the volume-pressure relationship and depends on the airway pressure reached.7-9 Also, a combination of small tidal volume and high PEEP was more effective than the opposite in promoting recruitment at a given maximal airway pressure. 10,11

47. Hastalarin % 70-75’i pulmoner ARDSHastalarin % 70-75’i pulmoner ARDS

48. Mortality tended to improve and extubation occurred earlier in the ARDS group, whereas the opposite trend was observed in the group with ALI but without ARDS. These results suggest that the strategy of a high level of PEEP and low tidal volume should be used with caution in patients with ALI not reaching the criteria for ARDS Our study has a number of limitations. The unblinded nature of the study, coupled with the use of adjunctive interventions left to the discretion of the attending physician in case of severe hypoxemia, could confound our results. Mortalitede azalma gösterilmese de bu çalisma önemli mesajlar tasiyor. ALI’de bu manevralarin (yüksek PEEP) yararsiz hatta zararli olabilecegi gibi.Mortality tended to improve and extubation occurred earlier in the ARDS group, whereas the opposite trend was observed in the group with ALI but without ARDS. These results suggest that the strategy of a high level of PEEP and low tidal volume should be used with caution in patients with ALI not reaching the criteria for ARDS Our study has a number of limitations. The unblinded nature of the study, coupled with the use of adjunctive interventions left to the discretion of the attending physician in case of severe hypoxemia, could confound our results. Mortalitede azalma gösterilmese de bu çalisma önemli mesajlar tasiyor. ALI’de bu manevralarin (yüksek PEEP) yararsiz hatta zararli olabilecegi gibi.

49. Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n=475). Atelectrauma may be mitigated by recruitment maneuvers (periodic hyperinflations) to open collapsed lung tissue and high levels of positive end-expiratory pressure (PEEP) to prevent further collapse. In theory, ventilation strategies that combine low tidal volumes with prevention of atelectrauma would be ideal for lung protection. Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n=475). Atelectrauma may be mitigated by recruitment maneuvers (periodic hyperinflations) to open collapsed lung tissue and high levels of positive end-expiratory pressure (PEEP) to prevent further collapse. In theory, ventilation strategies that combine low tidal volumes with prevention of atelectrauma would be ideal for lung protection.

50. Çalisma basladiktan 8 ay sonraki toplantida hedefi düsünerek PEEp düzeyleri artirilmis. Amato OLV çalismasinda Baslangiçta PEEP PV egrisine göre belirlenmis. Bu çalismada FiO2’ye göre (Tablodaki). Çalisma baslangicinda Amato’ya uygun olarak RM ile baslanmis: FiO2 % 100 ve 40 cmH2O basinç düzeyinde 40 sn nefes tutmaÇalisma basladiktan 8 ay sonraki toplantida hedefi düsünerek PEEp düzeyleri artirilmis. Amato OLV çalismasinda Baslangiçta PEEP PV egrisine göre belirlenmis. Bu çalismada FiO2’ye göre (Tablodaki). Çalisma baslangicinda Amato’ya uygun olarak RM ile baslanmis: FiO2 % 100 ve 40 cmH2O basinç düzeyinde 40 sn nefes tutma

53. Hangi hastalar yüksek PEEP’den yarar görebilirler? Dinamik AC görüntüleme teknikleri yayginlasana ya da yeni bir teknik bulunana kadar daha agir durumdaki hastalarin yüksek PEEP’den yarar görecegi Dinamik AC görüntüleme teknikleri yayginlasana ya da yeni bir teknik bulunana kadar daha agir durumdaki hastalarin yüksek PEEP’den yarar görecegi

54. Pao PEEPi + akima direnç + Ers Ers = Ecw + EL Obezite, gögüs duvari hasari, cerrahi pansuman, majör abdominal cerrahi Transpulmoner P (PL) = Pao – Ppl Transpulmoner P (PL) = Pao – (Pes - 5 cmH2O) Transpulm P pratikte ölçülmüyor. Pplat ve PEEP ölçülüyor. Ama bunlar da Ecw’u dikkate almiyor. 70 Hastada özofagus alt 1/3’e latex balon yerlestiriliyor Pressure inflating the lung during mechanical ventilation is the difference between pressure applied at the airway opening (Pao) and pleural pressure (Ppl). Depending on the chest wall’s contribution to respiratory mechanics, a given positive end-expiratory and/or end-inspiratory plateau pressure may be appropriate for one patient but inadequate or potentially injurious for another. Thus, failure to account for chest wall mechanics may affect results in clinical trials of mechanical ventilation strategies in acute respiratory distress syndrome. By measuring esophageal pressure (Pes), we sought to characterize influence of the chest wall on Ppl and transpulmonary pressure (PL) in patients with acute respiratory failure. Hastalardaki PEEP ve RM’lara farkli yanitin bir nedeni de gögüs duvarinin mekaniklerindeki farklar olabilir. Transpulmoner basinç ise alveoler basinçla, yada MV sirasinda monitorize edilen plato basinci ile plevral basinç arasindaki farktir. Transpulmoner basinç direk olarak akciger volümünü belirleyen, onunla yakin iliski içinde olan basinçtir. They used manometry to measure esophageal pressure (Pes) as a surrogate for Ppl. They subtracted 5 cm H2O from each value of Pes to correct for artifacts attributable to body position and balloon pressure. A possible interpretation of the discordant results (Cochrane’de), as proposed by Gattinoni (Gattinoni 2002), could involve variations of trans-pulmonary pressure, which is the distending force of the lung, in the individual patient. The high volume might induce lung damage when the resulting trans-pulmonary pressure is high. Conversely, when trans-pulmonary and airway pressure are within the safe limits, high or intermediate tidal ventilation (8 to 10 ml/Kg) could be used, thus avoiding potentially deleterious effects of low tidal volume, Thus, when chest wall compliance is low, a higher plateau pressure may be necessary to reach the same trans-pulmonary pressure, without increase in tidal volume. Transpulm P pratikte ölçülmüyor. Pplat ve PEEP ölçülüyor. Ama bunlar da Ecw’u dikkate almiyor. 70 Hastada özofagus alt 1/3’e latex balon yerlestiriliyor Pressure inflating the lung during mechanical ventilation is the difference between pressure applied at the airway opening (Pao) and pleural pressure (Ppl). Depending on the chest wall’s contribution to respiratory mechanics, a given positive end-expiratory and/or end-inspiratory plateau pressure may be appropriate for one patient but inadequate or potentially injurious for another. Thus, failure to account for chest wall mechanics may affect results in clinical trials of mechanical ventilation strategies in acute respiratory distress syndrome. By measuring esophageal pressure (Pes), we sought to characterize influence of the chest wall on Ppl and transpulmonary pressure (PL) in patients with acute respiratory failure. Hastalardaki PEEP ve RM’lara farkli yanitin bir nedeni de gögüs duvarinin mekaniklerindeki farklar olabilir. Transpulmoner basinç ise alveoler basinçla, yada MV sirasinda monitorize edilen plato basinci ile plevral basinç arasindaki farktir. Transpulmoner basinç direk olarak akciger volümünü belirleyen, onunla yakin iliski içinde olan basinçtir. They used manometry to measure esophageal pressure (Pes) as a surrogate for Ppl. They subtracted 5 cm H2O from each value of Pes to correct for artifacts attributable to body position and balloon pressure. A possible interpretation of the discordant results (Cochrane’de), as proposed by Gattinoni (Gattinoni 2002), could involve variations of trans-pulmonary pressure, which is the distending force of the lung, in the individual patient. The high volume might induce lung damage when the resulting trans-pulmonary pressure is high. Conversely, when trans-pulmonary and airway pressure are within the safe limits, high or intermediate tidal ventilation (8 to 10 ml/Kg) could be used, thus avoiding potentially deleterious effects of low tidal volume, Thus, when chest wall compliance is low, a higher plateau pressure may be necessary to reach the same trans-pulmonary pressure, without increase in tidal volume.

55. We found that Pes was on average unexpectedly high in our patients, averaging 17 cm H2O at end-expiration and 21 cm H2O at end-inflation, and Pes varied widely among patients with acute lung injury, both at end-inflation and at end-expiration (Fig. 2). We found that Pes was on average unexpectedly high in our patients, averaging 17 cm H2O at end-expiration and 21 cm H2O at end-inflation, and Pes varied widely among patients with acute lung injury, both at end-inflation and at end-expiration (Fig. 2).

56. Graphic representation of the stress index concept. The stress index is the coefficient b of a power equation (airway pressure 5 a inspiratory timeb 1 c), fitted on the airway opening pressure (Pao) segment (bold lines) corresponding to the period of constant-flow inflation (dotted lines), during constant-flow, volume-cycled mechanical ventilation. For stress index values of less than 1, the Pao curve presents a downward concavity, suggesting a continuous decrease in elastance during constantflow inflation. For stress index values higher than 1, the curve presents an upward concavity suggesting a continuous increase in elastance. Finally, for a stress index value equal to 1, the curve is straight, suggesting the absence of tidal variations in elastance. Graphic representation of the stress index concept. The stress index is the coefficient b of a power equation (airway pressure 5 a inspiratory timeb 1 c), fitted on the airway opening pressure (Pao) segment (bold lines) corresponding to the period of constant-flow inflation (dotted lines), during constant-flow, volume-cycled mechanical ventilation. For stress index values of less than 1, the Pao curve presents a downward concavity, suggesting a continuous decrease in elastance during constantflow inflation. For stress index values higher than 1, the curve presents an upward concavity suggesting a continuous increase in elastance. Finally, for a stress index value equal to 1, the curve is straight, suggesting the absence of tidal variations in elastance.

57. Ilk kez insanda deneniyor. Accordingly, in patients with a focal distribution of loss of aeration (i.e., with atelectatic dependent lobes coexisting with aerated nondependent lobes), the use of high PEEP levels (15–20 cm H2O) resulted in minimal alveolar recruitment in the dependent lobes but significant hyperinflation in the nondependent lung lobes (10). In the present study, we tested the hypothesis that ventilation using the standardized ARDSnet PEEP–FIO2 protocol would induce alveolar hyperinflation in patients with focal ARDS. Therefore, we compared in these patients the ARDSnet ventilatory strategy with an alternative strategy characterized by a more ‘‘physiologic’’ titration of PEEP, aimed at minimizing ventilator-induced tidal hyperinflation. To do so, we adjusted PEEP based on stress index monitoring, as recently proposed by De Perrot and colleagues and Ranieri and coworkers (11–13). The stress index is determined on a breath-by-breath basis during constant-flow ventilation by analyzing the shape of the inspiratory airway opening pressure curve. This approach assumes that, during constant-flow tidal inflation, the rate of change in airway opening pressure over time reflects the rate of change in elastance of the respiratory system (14). A recent CT study suggested that the stress index may accurately quantify the degree of tidal alveolar hyperinflation (15). Ilk kez insanda deneniyor. Accordingly, in patients with a focal distribution of loss of aeration (i.e., with atelectatic dependent lobes coexisting with aerated nondependent lobes), the use of high PEEP levels (15–20 cm H2O) resulted in minimal alveolar recruitment in the dependent lobes but significant hyperinflation in the nondependent lung lobes (10). In the present study, we tested the hypothesis that ventilation using the standardized ARDSnet PEEP–FIO2 protocol would induce alveolar hyperinflation in patients with focal ARDS. Therefore, we compared in these patients the ARDSnet ventilatory strategy with an alternative strategy characterized by a more ‘‘physiologic’’ titration of PEEP, aimed at minimizing ventilator-induced tidal hyperinflation. To do so, we adjusted PEEP based on stress index monitoring, as recently proposed by De Perrot and colleagues and Ranieri and coworkers (11–13). The stress index is determined on a breath-by-breath basis during constant-flow ventilation by analyzing the shape of the inspiratory airway opening pressure curve. This approach assumes that, during constant-flow tidal inflation, the rate of change in airway opening pressure over time reflects the rate of change in elastance of the respiratory system (14). A recent CT study suggested that the stress index may accurately quantify the degree of tidal alveolar hyperinflation (15).

58. Dependan akciger alanlarinda inspiratuar rallerin duyulmasi rekruitment – derekruitment belirtisi RM + PEEP’den yarar olasi Geç inspiryumda duyulan raller, daha yüksek basinçlarda açilan alanlarin göstergesi

59. RM (Hangi Hastada?) Geç dönemde RM basarili degil ve risk yüksek Grasso S. AJRCCM 2005; 171: 1002-1008 RM ekstrapulmoner ARDS’de daha etkin Lim CM. Crit Care Med 2003; 31: 411-418 Tugrul S. Crit Care Med 2003; 31: 738-744 KOAH’li hastalarda ve akciger absesi varliginda dikkat Verbrugge SJC, Lachmann B, Kesecioglu J. Clin Physiol Funct Imaging 2007; 27: 67-90 Recruitment strategies in a late phase of the disease process, when collapsed alveoli are being organized and infiltrated with fibroblasts are usually not possible and increase the risk of injury (Grasso et al., 2005). Moreover, lung recruitment may be more efficient in secondary ARDS (of extrapulmonary origin) in which a great part of collapsed lung is due to compression atelectasis; in primary ARDS (of pulmonary origin) in which an important reason for lung collapse in intrapulmonary oedema and inflammation, recruitment can be more difficult (Gattinoni et al., 1998; Pelosi et al., 1999; Lim et al., 2003). However, this distinction in response between primary and secondary ARDS could not be demonstrated in a recent paper by the Amato group (Borges et al., 2006). Patient categories in which a lung recruitment strategy should probably be conducted with great reserve include patients with severe airway obstruction/chronic obstructive pulmonary disease and patients with large pulmonary infiltrates of lung abscesses. Pulmoner ARDS’de Pulmoner kosolidasyon: Alveol ödem, fibrin, kollajen ve nötrofil agregatlari ile dolu Ekstrapulmoner ARDS’de ise interstisyel ödem mevcut, alveol içi rölatif olarak korunur. Recruitment strategies in a late phase of the disease process, when collapsed alveoli are being organized and infiltrated with fibroblasts are usually not possible and increase the risk of injury (Grasso et al., 2005). Moreover, lung recruitment may be more efficient in secondary ARDS (of extrapulmonary origin) in which a great part of collapsed lung is due to compression atelectasis; in primary ARDS (of pulmonary origin) in which an important reason for lung collapse in intrapulmonary oedema and inflammation, recruitment can be more difficult (Gattinoni et al., 1998; Pelosi et al., 1999; Lim et al., 2003). However, this distinction in response between primary and secondary ARDS could not be demonstrated in a recent paper by the Amato group (Borges et al., 2006). Patient categories in which a lung recruitment strategy should probably be conducted with great reserve include patients with severe airway obstruction/chronic obstructive pulmonary disease and patients with large pulmonary infiltrates of lung abscesses. Pulmoner ARDS’de Pulmoner kosolidasyon: Alveol ödem, fibrin, kollajen ve nötrofil agregatlari ile dolu Ekstrapulmoner ARDS’de ise interstisyel ödem mevcut, alveol içi rölatif olarak korunur.

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