Presented by Dr Gerry Capatos at the Egyptian ECMO Day 2017 held at Cairo, Egypt as part of the Egyptian Critical Care Summit .

1. Respiratory Failure in HIV: Why
ECMO?
Dr Gerry Capatos
Intensivist
Arwyp Hospital
Johannesburg

4. Current State of HIV in South Africa
• Human Sciences Research Council survey 2012:
• South Africa has the highest number of new HIV infections world-wide
• Increase in proportion of infected individuals in 2012 = 12.2% vs 10% in 2008
• 2012: 6.4 million infected people
• Highest infection rate in women aged 30-34 years, males aged 35-39 years
• Black African females aged 20-34 recorded the highest incidence of HIV
amongst all of the analysed population groups
•2012: 2 million patients on ARVs

5. Overview of our experience
• P. jirovecii pneumonia (PJP) remains one of the most common causes of
admission to ICU and ventilation in HIV positive patients
• Commonest cause of Acute Respiratory Failure in HIV patients
• In our experience, PJP may be the best indication for use of ECMO in AIDS
patients
• Other causes of respiratory failure may be carefully considered, including:
• Strep. Pneumoniae pneumonia, Tuberculosis, H1N1, other bacterial pneumonias
• VV ECMO was used for Acute Respiratory Failure in all of our patients.
• No patients were primarily treated for haemodynamic instabilityusing VA
ECMO.

6. In the Position Statement (2013) of the Critical Care Society of Southern Africa,
Extra Corporeal Membrane Oxygenation (ECMO) is NOT Recommended for:
• Pneumocystis jiroveci pneumonia requiring ventilation

8. Retrospective analysis of 22 HIV +ve patients requiring ICU admission to
private health care facilities
• 22 patients with severe ARDS, treated over 5 years
Variable N Mean Std Dev Median
Age 22 40.6 9.6 38.5
CD4 count on admission cells (cells/uL) 20 51.6 43.5 41
MurrayScore Pre-ECMO 17 3.3 0.2 3.5
Worst PF Ratio Pre-ECMO 22 95.6 56.4 79
Worst PaO2 Pre-ECMO (mmHg) 22 65.5 31.7 53.35
Worst pH pre-ECMO 22 7.3 0.1 7.33
Lowest systolicBP pre-ECMO 21 107.5 25.4 104
Duration ofECMO (days) 22 11.3 7.2 9.5
Duration ofICU stay(days) 22 23.1 15.0 18
MSOF Score at time of ECMO 21 2.0 0.9 2
Albumin Level at time of ECMO (g/L) 19 23.6 5.4 24
Duration ofVentilationin ECMOUnit 22 8.7 6.6 9
P = 0.020 r=0.53)

9. • The median duration of ECMO for those who survived
was 7 days, which was significantly shorter than for
those who died (13 days)
• (Wilcoxon rank sum test; p=0.020). The effect size
was moderate (r=0.53).
Died Survived

10. Why ECMO?
• Socioeconomic
• High mortality
• Developed countries : mortality = 85%
• Developing countries : nears 100%
• Prolonged hospital stay = increased cost (ECMO vs hospital stay)
• Significant morbidity
• Social catastrophe
• Since the availability of ARVs, outcomes have been improved in HIV
patients

11. EX: Foamy exudate
Pink arrows:Inflammationand cellularinfiltrate
F: fibrosis
Orange arrows:Type II pneumocyte proliferation
Blue arrows:normal alveolarwall and lining
Red arrows: scattered macrophages
Benfield T et al. CHEST 1997;111:1193-1199
Alveolar damage in AIDS-relatedPneumocystis carinii pneumonia
Why ECMO? Can one safely ventilate this kind of pathology?

12. Loss of Type I pneumocyte integrity
Thin arrows: Pneumocystisremains apposed to Type I pneumocytes
Thick arrows: Basement membrane left denuded

14. Shaddock EJ, Richards G, Murray J.
SAJHIVMED June 2012, Vol. 13,
No. 2

15. Remodelling
J Clin Invest. 2011; 121(6):2065–2073

16. Factors determining Mortality
(poorprognostic factors)
• Prolonged mechanical ventilation prior to commencement of ECMO
• Presence of multi-organfailure
• Multiple con-committantinfections (different organisms)
• Nosocomial Infections
• Require inotropic support prior to the initiation of ECMO
• Age
• Cachexia
• Pneumothorax
• LDH > 1000
• Note: CD4 count, PO2, Murray Scores were NOT used to predict which patients would have
poorer outcomes

17. High mortality factors in patients with PJP
Patients requiring MV despite having three days worth of
maximized appropriate treatment, including NIV
and who have a need for mechanical ventilation of more than
5 days,
have a predicted mortality of 80%

18. Factors associatedwith poor outcomes once
ECMO has commenced
• Duration of ECMO run
• Patients who survived had an ECMO run on average of 7 days
• Patients who died had an average ECMO run of > 13 days
• Inotropic support required while on ECMO

19. Improving Survival on ECMO
• Early extubation or ultra-protective ventilation
• ARVs (Morris A. et al, AIDS 2003;17:73-80)
• 25% mortality on ARVsand 63% NOT on ARVs
• Steroids (Gagnon S. et al. Engl J Med 1990;323:1444-50)
• Diagnosing of Cytomegalovirus co-infection and treatment

20. When should these patients be placed on
ECMO?
• EARLY intervention
• Rescue vs Salvage treatment
• Non-invasive ventilation failure
• Patients intubated for safety and safe cannulation

21. How should these patients be treated?
Awake ECMO
• Early Diagnosis and Early ECMO
• Awake ECMO : Control of Breathing
• Spontaneous Breathing
• Early Extubation
• Aggressive Mobilization
• “One Chance” – The patient becomes part of the Team

23. Langer T. et al Crit Care 2016; 20: 150

24. Dangers of Spontaneous Breathing
• Respiratory Distress may lead to worsening Trans-pulmonary
pressures due to extremely low pleural pressures
Langer T. et al Crit Care
2016; 20: 150

25. Spontaneous Breathing
• Eliminate contribution of ventilator to Trans-pulmonary pressure
• Excessive mechanical power
MauriT. et al IntensiveCareMed 22 June 2016
• Control work of breathing can control Trans-pulmonary pressure
(mean airway pressure – pleural pressure)
• Avoid ventilation induced lung injury
• Achieve low Driving Trans-pulmonary pressure (inspiratory T-
pulmonary pressure – expiratory T-pulmonary pressure) = GOLD
STANDARD
Kassis E. et al IntensiveCareMed 18 June 2016

26. Case Study: Severe PJP pneumonia

31. CT Scan pre discharge

33. Case 3
• 23 year old female patient
• Presented with confirmed PJP pneumonia (CD4 count 195
cells/uL)
• Patient started on PJP therapy and ARVs
• Failed NIV
• Decision taken to place on VV ECMO
• Able to extubate soon after cannulation
• Approximately 5 days later, work of breathing markedly
increased
• Needed re-intubation
• Soon after re-intubation,it was noted that she was having

35. CT Scan Brain

36. • Possibilities considered:
• Worsening condition due to super-imposed infections
• CMV PCR positive on Sputum: treatment started
• TB PCR negative on Sputum
• LP performed to exclude infection

37. • Most likely cause of deterioration IRIS (Immune Reconstitution
Inflammatory Syndrome)
• Pointers :
• Patient presented with an unusually high CD4 count for PJP
• Started on ARVs early
• Steroids dose
• No other infections found
• Aseptic picture on LP with high protein

38. In this case presentation the patient’s CD4 count was 33 cells / ml

40. Case Progress
• Patient improved on high dose steroids
• Never fully regained consciousness
• Died in septic shock after repeated episodes of sepsis
• Sputum Culture showed Candida Auris (moderate growth)
• At time of death CD4 count = 358 cells / uL

41. IRIS
• In patients with proven PJP
• Seen not long after initiation of ARVs
• Paradoxical deterioration: Pneumonitis
• Blood CD4 count raised
Barry SM et al. ImmuneReconstitution pneumonitis following Pneumocystis cariniipneumonia in HIV-infected subjects. HIV Medicine(2002), 3, 207-211

42. • Diagnostic on BAL fluid
• A) No pathogens seen
• B) Raise in CD4 and CD8 counts
There appears to be sequestration of CD4/8 cells in the lung, resulting in raised levels,
however, this is not always reflected in blood CD4 levels
• Response to Steroids
• Improvement on stopping ARVs

43. Worsening of PJP patient once on ECMO
• Jarisch – Herxheimer Reaction
• Re-perfusion injury
• Ventilation
• Drug pneumonitis (Abacavir)
• IRIS
• Nosocomial

46. Conclusions
• ECMO is a useful treatment modality in HIV with severe ARDS
providing that the diagnosis is potentially reversible.
• Low CD4 count solely, should not be an exclusionary criterion.
• ECMO in PJP with severe ARDS may not only be effective therapy, but
may also shorten ventilation and be cost effective
• In these patients, ECMO should be performed in experienced centres
for the best outcomes

47. Conclusions
• The concept of “early ECMO” may have applicability to other patients
requiring ECMO.
• Early extubation may be the ultimate form of lung protection if this is
possible.
• Patient recruitment improves outcomes and shorten length of stay
• Indications for ECMO could be patient specific, not ONLY pathology
specific.