Inhaled Nitric Oxide Beyond the Evidence- Children

Transcription

1 Critical Care Canada Forum, Toronto 2014 Inhaled Nitric Oxide Beyond the Evidence- Children Ian Adatia, Pediatric Pulmonary Hypertension Service and Cardiac Intensive Care Unit, Stollery Children s Hospital, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada. Fellow, Pulmonary Vascular Research Institute.

2 Nitric Oxide and Bob Dylan

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4 Ring: Unrubbed 2g Rubbed ACh min ACh W NA W NA -7.7 W Furchgott, Zawadzki 1980 Nature

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6 Pepke-Zaba, Higenbottam et al Lancet:1991:338:1173

7 Nitric Oxide Magic Bullet

8 Inhaled Nitric Oxide Decreases (selectively) Pulmonary Artery Pressure Improves Oxygenation Rapid Onset/Offset Inexpensive Favorable risk/benefit ratio Various intentional and unintentional factors influence beliefs beyond what scientific evidence justifies.

9 Beyond the evidence Strength of the belief exceeds the strength of the evidence Beliefs Low saturations are bad for patients Increased pulmonary aretry pressures are bad for patients Treating either or both is beneficial to patient outcomes

10 Wessel & Adatia Adv Pharmacol 1995:34:

11 Atz, Adatia, Wessel Ann Thorac Surg 1996: 62:1759

12 Courtesy David Wessel

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14 Effect of inhaled NO on PA pressure and Qs/Qt Adatia, Lillehei et al Ann Thorac Surg:1994;57:1311

15 Acetylcholine versus inhaled NO after cardiopulmonary bypass Percentage decrease in PVRI Preop Ach *p<0.002 **p< * ** Postop Ach Postop NO pmolm/l Wessel, Adatia et al Circulation:1993:88; Cyclic GMP Baseline With NO p<0.0001

16 Transpulmonary cgmp during NO inhalation cgmp pmol/ml Pulmonary artery Left atrium 0 baseline INO Post NO

17 Exhaled NO before and after surgical ASD closure Beghetti, Silkoff et al. Ann Thorac Surg 1998.

18 Exhaled NO after ASD closure * * Surgical closure Transcatheter closure * p<0.005 Humpl, Campbell et al J Thorac Cardiovasc Surg:2000:124:806

19 Endothelin and cgmp Christou, Adatia et al J Pediatr:1997:130:603

20 Journois, et al JTCVS 1994;107 Inhaled NO after cardiac surgery

21 Wessel, Adatia et al 2009

22 Withdrawal of NO rebound pulmonary hypertension Atz, Adatia, Wessel Ann Thorac Surg:1996:62:1759

23 Inhaled NO Randomized double blind study NO group fewer PHTN crises Consistently decreased PVRI Shorter time to reach extubation criteria Miller,Tang et al Lancet:2000:356;1464

24 Inhaled NO and hyperventilation Inhaled NO and hyperventilation decrease PVRI Hypocarbic alkalosis decreases CI and increases SVRI Morris, Beghetti et al Crit Care Med:2000:28:2974

25 Inhaled NO Miller, Celermajer et al J Thorac Cardiovasc Surg:1994:108:487

26 Why does ino not work?

27 Pediatr Hematol Oncol. 2007; 24(3): Kato, Onyekwere, Gladwin

28 Proposed natural history of left to right shunts Reversible Non reversible

29 Kulik, Mullen, Adatia. Prog Pediatr Cardiol:2009:27:25

30 DuShane et al., in The Child With Congenital Heart Disease After Surgery, Kidd and Rowe, 1976

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32 Acute Vasoreactivity

33 Positive response to AVT Negative response to AVT Time (Years)

34 Long Term Prostanoid Therapy... David B Badesch, Vallerie V McLaughlin, Marion Delcroix, CarmineDario Vizza, Horst Olschewski, Olivier Sitbon... Prostanoid therapy for pulmonary arterial hypertension Journal of the American College of Cardiology, Volume 43, Issue 12, Supplement, 2004, S56 - S61

35 Right ventricular pressure tracings Peter Harris Br Heart J 1955:17:

36 Why do patients with PAH die?

37 Why do patients with PAH die?

38 Left Upper Lobe Hematoma Pleural Defect, LUL

39 Why do patients with PAH die?

40 Survival in Pediatric PAH Prior to Availability of Targeted 100% Therapies 90% 80% Survival 70% 60% 50% 40% 1991 D Alonzo (NIH) 1999 Barst (without epo) 1995 Sandoval (Mexico) 1999 Barst (NR) 30% 1999 Van Loon 20% 10% 0% 1993 Houde (Toronto) Years Historical Controls Courtesy Robyn Barst

41 Variability of Improved Survival in Pediatric PAH in the Current Era 100% 1999 Barst (epo) 2010 Ivy 2008 Van Loon (prev) 90% 2010 Fraisse (France) 2006 Bosentan 2010 Moledina 2010 Barst (REVEAL) 2004 Yung Survival 80% 70% 60% 50% 40% 1991 D Alonzo (NIH) 1999 Barst (without epo) 2009 Haworth IPAH 2010 Berger 2009 Haworth APAH 1995 Sandoval (Mexico) 1999 Barst (NR) 2008 VanLoon (inc) 1999 Van Loon 30% 20% 10% 0% 1993 Houde (Toronto) Years Historical Controls Courtesy Robyn Barst

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43 26 patients Adatia, Atz, Wessel J Thorac Cardiovasc Surg 2004

44 Arterial ph Arterial PaCO 2 (mm Hg) *p= p= p= *p= p= p= PaCO 2 35 PaCO 2 45 PaCO 2 55 PaCO 2 40 PaCO 2 35 PaCO 2 45 PaCO 2 55 PaCO 2 40 Systemic Oxygen Saturation (%) Arterial PaO 2 (mm Hg) *p=0.029 p=0.30 p=0.014 *p= p= p= PaCO 2 35 PaCO 2 45 PaCO 2 55 PaCO 2 40 PaCO 2 35 PaCO 2 45 PaCO 2 55 PaCO 2 40

45 Episodic pulmonary hypertension and increased atrial pressures after heart transplant

46 Post operative pulmonary hypertensive crises?

47 Belief beyond the evidence: breakfast, obesity and bias Brown AM, Am J Clin Nutr:2013:98:1298

48 Inhaled NO beyond the evidence Medical decision-making in individual patients uses the findings of population-based evidence in guidelines, but the recommendations should be translated to an individual patient with unique needs and preferences. Moreover, personal experiences and interests of the health care provider and ethical principles together with economic and political considerations influence the ultimate decision. These factors cannot be quantified against each other, as they are difficult to balance. The World Health Organisation recognises this dilemma and advises that value judgements should be explicit and be influenced by patients in particular.

49 Conclusions Inhaled nitric oxide reverses acute vasoconstriction Often acutely improves oxygenation Rarely harmful acutely