Carbon Dioxide in Critical Care – Aim high???

Dr Ravi TiruvoipatiDepartment of Intensive Care Medicine

Frankston Hospital Frankston, VIC

CO2 in Critical Care

• Conflict of interest: None

Effects of CO2- Global

Should we aim for high CO2 in critically ill ?

• Lung protective ventilation has reduced mortality in patients with ARDS.

• May cause hypercapnia and acidosis ( ? an adverse effect).

• 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

– Evidence from animal experimental studies

– Clinical evidence (observational and RCT)

Effects of Hypercapnia in Experimental Lung Injury

• Extensively studied

• Conflicting results

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

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

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

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

Data from RCTs

• Hypercapnic acidosis may be harmful

• 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.)

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.

• 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)

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

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

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

• 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

• 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)

• 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

• 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)

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

<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 MortalityC

arb

on

dio

xid

e (m

mH

g)

pH

• 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.

Thank you

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.

• Increasing use, improving equipment

• Invasive and complex system

• Large cannulae.

• Systemic heparin

• Limited availability

ECMO

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.

Novalung -Disadvantages

• Lower limb ischemia if used for a prolonged period of time.

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

Decap® Smart

• Modification CRRT machine

• Single double-lumen cannula inserted in the femoral vein

• Blood flow 0- 450 ml/min.

Hemolung – Respiratory Dialysis

• One 15.5 Fr venous catheter

• Blood flow rates of 350 – 550 mL/min

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

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

RCTs Evaluating Low Flow Extracorporeal Gas Exchange

Devices

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

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

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.

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

• Facts: – CO2 causes global warming!

– CO2 increases mortality in patients with ARDS!!!

Let’s Clear it

Acknowledgements

• A/Prof John Botha

• A/Prof David Pilcher

• A/ Prof Michael Bailey

• Mr Glenn Eastwood