Presentation of Dr. Lluis Blanch at 10th Pulmonary Medicine Update Course, Cairo, Egypt. Pulmonary Medicine Update Course is organized by Scribe : www.scribeofegypt.com

1. Lluís Blanch M.D., Ph.D. Consultant Critical Care Scientific Director Corporació Parc Taulí Universitat Autónoma de Barcelona Sabadell, Spain. Cairo 3 - 4 February 2010 Advances in Pulmonary Critical Care: A 25 Years Perspective 10th Pulmonary Medicine Update Course

4. Fan E, et al. JAMA 2005;294:2889-96 Diagnostic Criteria for ARDS

5. Severe intra-alveolar infiltrates, deposition of hyaline membranes, vascular congestion and microthrombi. Human ARDS Matute-Bello G, et al. http://www.thoracic.org LPS inhaled OAI i.v. CLP sepsis Models of ARDS

6. American–European Consensus Conference Definition and Sensitivity, Specificity, and Likelihood Ratios Assessed in Patients Who Died in the Intensive Care Unit Reference Standard: Diffuse Alveolar Damage at Autopsy The accuracy of the American–European Consensus Conference definition of ARDS was only moderate. The definition was more accurate for patients with extrapulmonary risk factors than for patients with pulmonary risk factors.

10. Effects of NO on PaO2/FiO2 Effects of NO on Renal Dysfunction

11. Effects of NO on Mortality

12. … the effect of aerosolized and/or systemic vasodilators must be weighed against their net effect on heart, lung, and whole-body oxygenation. In other words, if a vasodilator moderately worsens oxygenation and shunt fraction but improves RV performance without marked effects on oxygen delivery to peripheral tissues in a patient with ARDS and severe pulmonary artery hypertension, it is probably safe to continue treatment under strict monitoring and clinical control…

14. Am J Resp Crit Care Med 2006;173:1233-39 ARDS patients FiO2 0.85, VT 8 ml/kg, PEEP 12 SAPS 38 – 42 & Diffuse Infiltrates Enrolled 48 h Prone 20 h/day A total of 718 turning procedures were done and PP was applied for a mean of 17 h/day. A total of 28 complications were reported, most rapidly reversible.

15. Spanish Trial: Kaplan-Meier Estimates of ICU Survival (up to 60 days) 25% ↓ Mortality in Prone Probability of Survival 10 20 30 40 50 60 Days After Randomization 0 20 40 60 80 100 SUPINE PRONE p= 0.27

16. JAMA 2009;302:1977-84 Moderate Hypoxemia Severe Hypoxemia

17. Crit Care Med 2001; 29:2251–2257

18. 311 pts with ARDS At Randomization: VT 9 ml/kg , PEEP 14 cmH 2 O Pplat 30 cmH 2 O Day 28 Ventilator-free days Mortality % CMV 13  9 15 Low dose PLV group 7  9* 26 High dose PLV group 10  9* 19

19. Pulmonary Edema Formation in Congestive Heart Failure & ARDS Piantadosi CA, Schwartz DA. Ann Intern Med 2004; 141:460-470.

21. Main Outcome Variables

22. B-agonists can enhance alveolar fluid clearance through the up-regulation of sodium transport mechanisms located on the alveolar epithelial cells. Objective & Methods: manipulation of alveolar fluid clearance with B-agonists can accelerate the resolution of alveolar edema. 40 pts.with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 g kg -1 h -1 ) or placebo for 7 d. Results: Patients in the salbutamol group had lower extravascular lung water, plateau pressure and LIS at day 7 compared with placebo group.

23. Amato M, Marini JJ. Barotrauma, volutrauma, and acute lung injury. In: Physiological Basis of Ventilatory Support. Marini J, Slutsky A, eds. Marcel-Dekker 1998. Disposition of Surfactant Molecules during Tidal Ventilation without PEEP

24. CHEST 2008; 134:724–732 Pooled analysis included exclusively trials using recombinant surfactant protein-C (rSP-C) surfactant (Venticute) for intratracheal instillation in patients with ARDS. All five multicenter, randomized trials were conducted between 1998 and 2001, and represent all patients ever included in completed ARDS trials using this compound. Direct ARDS

25. Am J Respir Crit Care Med Vol 180. 989–994, 2009 418 patients with ALI/ARDS randomly assigned to receive usual care either with or without instillation of exogenous natural porcine surfactant HL 10 as large boluses at 0, 12 and 36 h.. The study was prematurely terminated because safety analysis showed a trend toward higher mortality in the treatment group Usual care Surfactant

26. ARDS & Inflammation & NF-kb IKK NIK MEKKs Degradation IkB Transcription Activation Second Mesengers Oxidative Stress Steroids inhibit nuclear transcription of NF-kb IkB NF-kb NF-kb NF-kb Cytokines Molec Adh Others TLR IL-1R TRAF Rupture MP Integr.csk

27. doi:10.1136/bmj.39537.939039.BE Steroids to Prevent ARDS

28. N Engl J Med 2008;358:111-24. CORTICUS Study 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days. Adverse events no difference in: Multiple organ systen failure OR 1.2; IC 95% 0.66-1.58. Pulmonary dysfunction OR 0.61; IC 95% 0.26 -1.44.

29. Steroids in Persistent ARDS Participants: 24 patients with severe ARDS who had failed to improve LIS at day 7. Interventions: 16 patients received methylprednisolone (2mg/kg for 32 d) and 8 received placebo. Outcome Clinical Evolution

30. Rationale : Persistent ARDS is characterized by ongoing inflammation, parenchymal-cell proliferation and disordered deposition of collagen all of which may be responsive to corticosteroid therapy.

31. Main Outcome Variables

32. doi:10.1136/bmj.39537.939039.BE

33. Crit Care Med 2009; 37:1594 –1603 Effect of Steroid on Mortality

34. Crit Care Med 2009; 37:1594 –1603 & Complications p=NS

35. Objectives: To determine the incidence and outcomes of ICU-acquired neuromyopathy and to investigate the role of methylprednisolone in survivors of persistent acute lung injury. Participants: Patients enrolled in the ARDS Network study of methylprednisolone versus placebo for persistent ARDS who survived 60 days or to hospital discharge. Results: 128 patients survived 60 days and 44 (34%) had evidence by chart review of ICU-acquired neuromyopathy, which was associated with prolonged mechanical ventilation, return to mechanical ventilation, and delayed return to home. Treatment with methylprednisolone was not significantly associated with an increase in risk of neuromyopathy (OR 1.5; 95% CI 0.7–3.2).

37. AJRCCM 2008;178:618–623 75 patients were randomized to receive APC (24 mg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days.

40. Assessing practice changes 1998 (1.383 p.) 2004 (1.675 p.)

43. Chronological Distribution Objective: To assess unintended events that compromise patient safety Methods: During 24 h. events were reported by ICU staff members In 1,913 adult patients a total of 584 events affecting 391 patients were reported. During 24 h multiple errors related to medication occurred in 136 patients; unplanned dislodgement or inappropriate disconnection of lines, catheters, and drains in 158; equipment failure in 112; loss, obstruction or leakage of artificial airway in 47; and inappropriate turn-off of alarms in 17.

44. The design of the user interface is relevant to the occurrence of operational failures. Ventilator designers could optimize the user-interface design to reduce the operational failures. Basic user interface should be standardized among mechanical ventilators Respir Care 2008;53(3):329 –337.

45. Critical care medicine is the specialty that cares for patients with acute life-threatening illnesses where intensivists look after all aspects of patient care. Nevertheless, shortage of physicians and nurses, the relationship between high costs and economic restrictions, and the fact that critical care knowledge is only available at big hospitals puts the system on the edge. In this scenario, telemedicine might provide solutions to improve availability of critical care knowledge where the patient is located, improve relationship between attendants in different institutions and education material for future specialist training . Current information technologies and networking capabilities should be exploited to improve intensivist coverage, advanced alarm systems and to have large critical care databases of critical care signals. The Open Respiratory Medicine Journal, 2009, 3, 10-16

46. Mortality among ICUs before and after Tele-ICU