Abdul Muthalib, Hani Lababidi, Abdul Waheed Mir, Ahmed F Al Ohali, Nasser Al Hamoud, Ahmed M Al Enezi. Dept. of Pulmon

1. “ Preliminary Experience with Airway Pressure Release Ventilation (APRV) on the Hemodynamics in Patients with Septic Shock in a Medical/Surgical Intensive Care Unit” Abdul Muthalib, Hani Lababidi, Abdul Waheed Mir, Ahmed F Al Ohali, Nasser Al Hamoud, Ahmed M Al Enezi. Dept. of Pulmonary & Critical Care Medicine, King Fahad Medical City, Riyadh, KSA.

2. Introduction • The effects of positive pressure ventilation on hemodynamic parameters are known to be complex. • They are determined by an integral relationship between vascular resistance and intrathoracic pressure. • M. R. Pinsky et al; “The hemodynamic consequences of mechanical ventilation: an evolving story,” Intensive Care Medicine, vol. 23, no. 5, pp. 493–503, 1997. • M. R. Pinsky etal, “Cardiovascular issues in respiratory care,” Chest, vol. 128, no. 5, pp. 592S–597S, 2005.

3. Hemodynamic Effect of Positive Pressure Ventilator Positive Pressure Ventilator Intrathoracic Pressure Rt. Atrial Pressure Venous Return RV Filling LV Preload LV Contractility to compensate SV

4. Introduction • Currently there is an increasing use of non-conventional ventilator mode in modern Intensive Care Unit (ICU). • Of which, one is • Airway Pressure Release Ventilation (APRV) • It allows spontaneous breathing throughout the ventilation cycle.

5. Thigh Tlow Phigh Plow AirwayPressureReleaseVentilation (APRV) Continuous positive airway pressure (CPAP) with regular, brief, intermittent releases in airway pressure Stock, Downs, Frolicher: Crit Care Med, May 1987

6. APRV • APRV increases venous return and cardiac index which will may significantly improve organ perfusion. • This is could be important in septic shock to prevent extra thoracic organ system failure secondary to poor perfusion.

7. PCV APRV Airway Pressure Release Ventilation Enhances Cardiac Performance in Patients with ALI/ ARDSKaplan, Bailey, Formosa: Crit Care 2001 • Syndow et al, AJRCCM 1994. • Putensen ,et al AJRCCM, 159,1999. • Hering et al, Crit Care Med 2002

8. Research Questions Primary Hypothesis: Would the use of APRV in septic shock patient restore hemodynamic stability earlier than CMV mode? Secondary Hypothesis: Would the use of APRV in septic shock patients improve their survival in ICU?

9. Materials & Methods • Obtained our IRB approval • Retrospective study of the clinical data of septic shock patients who received ventilator support between January and December of 2011 in med-surg ICU at KFMC, Riyadh.

10. Inclusion Criteria Patients with septic shock who required ventilatory support who received either APRV or CMV (Dragger Evita XL) ventilatory support.

11. Exclusion Criteria • Less than 18 yrs old • Trauma and closed head injury • Readmission to ICU • Patients not for resuscitation (DNR) • For patient with multiple admission to ICU, only the last admission was considered.

12. Definitions • Septic Shock : SBP < 90 mmHg or < MAP 65 mmHg or a reduction in SBP > 40 mm Hg from baseline despite adequate volume resuscitation • Reversal of shock: SBP >90 or MAP 65mmHg without vasopressor support for at least 24 hours • Organ dysfunction: SOFA score ≥ 2 for each organ. • Severity of illness: APACHE II Score before ventilator support • Management of septic shock: Septic shock bundle based on early goal- directed therapy (EGDT)

13. Data Collection • Patients were identified through a prospectively collected ICU log book. • Charts were reviewed and data points were documented with help of patient file, Cortex system, ICU log book, and HIM chart viewer.

14. Data Collection • The severity of illness was assessed by Acute Physiology and Chronic Health valuation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score. • Hemodynamics parameter: • Pre ventilator ( HR, SBP, DBP, MAP and CVP). • Post ventilator period assessment of maximum duration • of vasopressor distribution between the groups • Reversal of shock before 72 hours • Number of patient required vasopressor by Day 7 • Survival to ICU discharge

15. StatisticalAnalysis: • Mann-Whitney U-test for continuous variables • Fisher’s exact test for categorical variables. • Cox proportional hazard model (Co-morbid, Glasgow Coma Scale, vasopressor, and age) • Nonparametric Wilcoxon rank sum test used to assess significant outcome differences between groups • Kaplan-Meir method was used to analyze Time to event/survival. • P-value considered significant if it is equal or less than 0.05 • SAS Version 9.3 (SAS Institute, Inc., Cary, North Carolina).

16. Total 328 septic shock patients admitted between Jan 2011 and Dec 2011 58 patients excluded: Incomplete patients data  28 Do Not Resuscitation (DNR)  16 Readmission to ICU 11 Head injury  4 Ventilated septic shock patient total 187 Study Population 129 APRV 38 CMV 91 Results: Study flow diagram:

17. Results: Patients Demographic aAppropriate antibiotics were based on the site of infection and available culture, *Fisher exact test, ‡ Mann-Whitney rank sum test.

18. Results: Baseline and prognostic characteristics at the time of initiation of ventilator support between two groups 95% CI – 95% Confident Interval

19. Results: Confounder factors

20. Results: Wilcoxon Scores (Rank Sums test)  graph for Vasopressor Maximum hours distribution between the groups. P= 0.010 P= 0.0214

21. Results: Kaplan-Meier Curve 75% of CMV group required Inotrops support till Day 7, in APRV only 45% needed Inotrops support.

22. Results: Reversal of shock within 72 Hrs was highly significant between two groups. APRV n=16(42%) & CMV n=8(9%) P=0.0001

23. Results: Survival outcome Proportion of survival after initiation of ventilator therapy was higher in APRV than CMV group (71% vs 49%, P<0.0001).

24. Results: Kaplan-Meier Curve Survival Probability between two groups. Patient who Survived between groups are statistically significant (P=0.0201) Kaplan-Meier survival analysis comparing ventilated septic shock patients treated with APRV and CMV mode (solid blue line represents the APRV group and dotted red line represents CMV group)

25. Results: Survival Outcome between APRV and CMV group ‡‡ Wilcoxon Scores - Rank Sums Test, * Fisher's Exact Test

26. Limitation of the study The retrospective nature of this report prevents direct comparisons between APRV and CMV. 2. Patients may have been selected for APRV on the basis of risk factors and severity of illness, introducing potential selection bias 3. Other confounders variables like hospital admission time, ICU staffing, etc. that may play a role in the observed differences

27. Conclusion • The use of APRV in septic shock patients restore hemodynamic stability earlier than CMV mode • There was a significant improvement in ICU survival by using APRV over CMV • Early initiation of APRV in ventilated septic shock patient was associated with decrease in ICU mortality • APRV is a promising mode, and further research is needed to strengthen support for its more widespread use • Prospective studies are needed to further validate our findings

28. Conflict of Interest The author declares that they have no competing interests. Authors’ contributions AM was responsible for study design, interpretation of data and analysis, and manuscript writing. He takes full responsibility for the integrity of the study. AAE was responsible for study design, data analysis, and manuscript revision. HL was responsible for study design, data analysis, Interpretation and manuscript revision. All authors read and approved the manuscript.

29. Thank you for your attention