ICN Victoria presents Associate Professor Ravi Tiruvoipatl talking onCO2 management in critical care.

1. Carbon Dioxide in Critical Care
– Aim high???
Dr Ravi Tiruvoipati
Department of Intensive Care Medicine
Frankston Hospital
Frankston, VIC

2. CO2 in Critical Care
• Conflict of interest: None

3. Effects of CO2- Global

7. Should we aim for high CO2 in
critically ill ?

8. • Lung protective ventilation has
reduced mortality in patients with
ARDS.
• May cause hypercapnia and acidosis
( ? an adverse effect).

9. • Some suggest hypercapnia and acidosis may be
protective by itself
• Hypothesise that inducing hypercapnia by
supplemental carbon dioxide may be beneficial
• To the contrary many consider hypercapnic acidosis
to be harmful

10. –Evidence from animal experimental
studies
–Clinical evidence (observational and
RCT)

11. Effects of Hypercapnia in Experimental Lung Injury
• Extensively studied
• Conflicting results

12. Beneficial Effects in Animal Models
• Rabbit model of ischemia and reperfusion injury
– Attenuated pulmonary inflammation and preserved lung
mechanics
– Buffering hypercapnic acidosis worsened lung injury
• Rabbit model of endotoxin induced lung injury
– Attenuated lung injury by reducing inflammation via inhibition
of NF-kappaB activation
• In vivo rat model of endotoxin / sepsis induced lung
injury- attenuated lung injury

13. Harmful Effects in Animal Models
• In vivo rat model of HCL induced lung injury
– Worsens lung injury with hemodynamic instability
• In vivo rat model of E coli sepsis induced lung
injury
– Worsens lung injury

14. Harmful Effects in Animal Models
• Ex vivo perfused rat lung model of ventilator
induced lung injury
– Reduces wound repair in alveolar epithelial cells
• Isolated rat lung model
– Impairs alveolar epithelial cell function

15. Observational Studies
• Hickling et al (1990)
– Retrospective review of 50 patients with ARDS
– Limiting airway pressures and accepting hypercapnia
showed an improved survival (compared with APACHE II
predicted mortality).
• Kregenow et al (2006)
– hypercapnic acidosis was associated with reduced 28-day
mortality in the 12 mL/kg
– no survival benefit in patients ventilated with lung
protective tidal volumes

16. Data from RCTs
• Hypercapnic acidosis may be harmful

17. • Multicentre RCT
• 120 patients
• Peak inspiratory pressure < 30 (tidal vol 8 ml
or less) Vs up to 50 cm of water (tidal vol 10-
15 ml)
• Allowed pH to drop till 7.0 (allowing
permissive hypercapnic acidosis)
(N Engl J Med 1998; 338:355-61.)

22. Reasons for increased incidence of AKI
• A variety of factors (lower pH due to respiratory
acidosis) could have resulted in the use of dialysis
• Permissive hypercapnia had a direct role, since
carbon dioxide has known vasoactive properties
that may have impaired renal blood flow, leading,
in turn, to the need for dialysis.

24. • Multi-center RCT comparing low plateau pressure (25
cm H2O, VT <10 ml/kg) versus VT >/=10 ml/kg.
• Permissive hypercapnia with pH > 7.05
• Planned sample size 240 patients (recruitment stopped
after 116 patients)

26. Trend towards higher mortality in patients with pressure limited
ventilation (46.6% versus 37.9% in control subjects)

27. • Possible increase in mortality due to
permissive hypercapnia and hypercapnic
acidosis

28. Prospective, randomized, controlled clinical trial
comparing traditional versus reduced tidal volume
ventilation in acute respiratory distress syndrome
patients.
Brower RG, et al Critical Care Medicine 7(8), 1999, pp
1492-1498

29. • Prospective, Multicentre RCT
• Tidal volume 10-12 mL/kg (Plateau pressure <55
cm) Vs. tidal volume 5-8 mL/kg (< 30 cm)
• Planned sample size 130, but stopped at 52

31. • There were no significant differences in
– Use of vasopressors, sedatives, or neuromuscular blocking
agents,
– Ventilator days,
– Mortality (46% in the high volume group and 50% in low
volume group)

32. • 2 centre study; 53 patients with ARDS
• Conventional arm
• Tidal volume of 12 ml and normal arterial carbon dioxide levels
(35 to 38 mm Hg).
• Protective ventilation
• Tidal volume of less than 6 ml
• pH>7.2, HCO3 infusions PRN

35. • Multicentre RCT; 6 ml Vs 12 ml/KGBW
• Strict control of acidosis aiming for near normal
CO2 and pH (increasing ventilator rate and
bicarbonate infusions)
• Mortality (31.0 percent vs. 39.8 percent, P=0.007)

38. Data from ANZIC APD
• Data from 2000 to 2010
• Total of 304696 ventilated patients
• Aim to assess the impact of CO2 and pH on
hospital mortality

39. <7.24 7.24-7.30 7.31 - 7.36 7.37 - 7.42 >7.42
<34 2.77 2.73 2.57 2.26 2.25
34-38 1.91 1.53 1.35 1.18 1.35
38-42 1.87 1.23 0.97 0.84 1.33
42-49 1.55 1.09 0.95 1 1.95
>49 1.47 1.46 1.42 1.64 2.2
Odds Ratios For Hospital MortalityCarbondioxide(mmHg)
pH

40. • In summary,
– the effects of hypercapnia and hypercapnic
acidosis remain unclear, but potentially harmful.
– the effect of low volume ventilation was proved to
be beneficial, but only when pH and pCO2 were
maintained close to normal.

41. Thank you

42. Carbon Dioxide Clearance Techniques
• Possible options
– ECMO
– Low flow extracorporeal gas exchange devices - Partial
support
• Interventional Lung Assist (ILA) (NovaLung GmbH)
• Low flow venovenous extracorporeal carbon dioxide
removal
• Decap Smart
• Hemolung.

43. • Increasing use, improving equipment
• Invasive and complex system
• Large cannulae.
• Systemic heparin
• Limited availability
ECMO

44. Pump Less Arteriovenous Interventional Lung Assist: Novalung
• Experience in over 1800
patients
• Arterial(15F) and venous (17F)
cannulation
• Blood flow by AV pressure
gradient. No pump and heat
exchanger
• Blood flow 1- 2.5 LPM.

45. Novalung -Disadvantages
• Lower limb ischemia
if used for a
prolonged period of
time.

47. Minimally Invasive CO2 Removal
• Main features of this system as opposed to the
ECMO or iLA NovaLung are
– Less invasive, no need for arterial cannulation
– lower blood flow (200-500 mL/min)
– Small oxygenator
– Smaller double-lumen catheters

50. Decap® Smart
• Modification CRRT machine
• Single double-lumen cannula
inserted in the femoral vein
• Blood flow 0- 450 ml/min.

51. Hemolung – Respiratory Dialysis
• One 15.5 Fr venous
catheter
• Blood flow rates of
350 – 550 mL/min

52. Low Flow Extracorporeal Gas Exchange Devices-
Reported uses
• Acute severe asthma
• Support of ALI/ARDS patients
• Neurosurgery patients with ARDS with repeated
intracranial bleeds
• Inter-hospital transfers of patients
• Bridge to lung transplant

53. Low Flow Extracorporeal Gas Exchange Devices-
Reported uses
• Post pneumonectomy ARDS patients
• Diffuse alveolar haemorrhage
• Traumatic head injury patients
• Complex thoracic surgical procedures
• Downgrade from ECMO

54. RCTs Evaluating Low Flow
Extracorporeal Gas Exchange
Devices

55. Extrapulmonary Interventional Ventilatory Support in Severe ARDS
(Xtravent)
• Multicentre RCT investigating the effects
‘Novalung’on the implementation of a lung-protective
ventilatory strategy in patients with ARDS.
• The duration of ventilation, intensive care and hospital
stay and in-hospital mortality were investigated.
• N= 120, completed last year… results awaited

56. Low-flow ECCO2-R and 4 ml/kg vs. 6 ml/kg Tidal Volume to
Enhance Protection From VILI in Acute Lung Injury (ELP)
• Multicenter RCT
• Control of PaCO2 in the ~4 ml/kg arm accomplished by ECCO2-R.
• Primary outcome measure
• Ventilator free days during the 28 days post randomisation
• Secondary outcome measures
• 28 day, 90 day mortality, ICU free days at 28 days

57. Extracorporeal CO2 Removal in COPD Exacerbation (DECOPD)
• Multi-center experimental single study
• Efficacy of the ‘Decap Smart’in
– reducing the intubation rate or
– the duration of invasive mechanical ventilation in
COPD patients
• Currently recruiting
• Planned sample size 20 patients.

58. Future
• Low flow partial support devices may become
a standard practice in most of the ICUs
(similar to RRT)
• These devices may
– aid in instituting lung protective / ultra protective
ventilation
– reduce the need for mechanical ventilation
– reduce the need for ECMO for respiratory support

59. • Facts:
– CO2 causes global warming!
– CO2increases mortality in patients with ARDS!!!
Let’s Clear it

60. Acknowledgements
• A/Prof John Botha
• A/Prof David Pilcher
• A/ Prof Michael Bailey
• Mr Glenn Eastwood