ICN Victoria - Ravi Tiruvopati on CO2 in Critical Care
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Carbon Dioxide in Critical Care – Aim high???
Dr Ravi TiruvoipatiDepartment of Intensive Care Medicine
Frankston Hospital Frankston, VIC
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CO2 in Critical Care
• Conflict of interest: None
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Effects of CO2- Global
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Should we aim for high CO2 in critically ill ?
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• Lung protective ventilation has reduced mortality in patients with ARDS.
• May cause hypercapnia and acidosis ( ? an adverse effect).
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• 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
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– Evidence from animal experimental studies
– Clinical evidence (observational and RCT)
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Effects of Hypercapnia in Experimental Lung Injury
• Extensively studied
• Conflicting results
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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
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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
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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
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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
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Data from RCTs
• Hypercapnic acidosis may be harmful
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• 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.)
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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.
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• 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)
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Trend towards higher mortality in patients with pressure limited ventilation (46.6% versus 37.9% in control subjects)
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• Possible increase in mortality due to permissive hypercapnia and hypercapnic acidosis
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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
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• 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
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• 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)
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• 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
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• 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)
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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
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<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
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• 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.
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Thank you
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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.
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• Increasing use, improving equipment
• Invasive and complex system
• Large cannulae.
• Systemic heparin
• Limited availability
ECMO
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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.
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Novalung -Disadvantages
• Lower limb ischemia if used for a prolonged period of time.
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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
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Decap® Smart
• Modification CRRT machine
• Single double-lumen cannula inserted in the femoral vein
• Blood flow 0- 450 ml/min.
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Hemolung – Respiratory Dialysis
• One 15.5 Fr venous catheter
• Blood flow rates of 350 – 550 mL/min
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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
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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
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RCTs Evaluating Low Flow Extracorporeal Gas Exchange
Devices
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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
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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
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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.
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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
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• Facts: – CO2 causes global warming!
– CO2 increases mortality in patients with ARDS!!!
Let’s Clear it
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Acknowledgements
• A/Prof John Botha
• A/Prof David Pilcher
• A/ Prof Michael Bailey
• Mr Glenn Eastwood