Permissive Hypercapnia in ARDS

Dr Swapnil Pawar February 3, 2020 4570 4

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Lung protective ventilation has become the cornerstone of the management of ARDS patient. As a consequence, hypercapnia is inevitable. However, permissive hypercapnia is not without its own problems. In this podcast, we discuss this dogma and challenge traditional practices. 

What is permissive hypercapnia?

Permissive hypercapnia is a ventilation strategy that allows an unphysiologically high partial pressure of carbon dioxide (PCO2) to permit lung protective ventilation with low tidal volumes. The term “permissive hypercapnia” was coined by Hickling and associates in the early 1990s in their seminal descriptions of improved survival in ARDS in which plateau pressures and tidal volumes were limited. Thus, from the 1990s, lung-protective ventilation using low tidal volumes and limitation of plateau pressures emerged as a pivotal strategy in patients with acute respiratory failure, especially with acute respiratory distress syndrome (ARDS), who undergo mechanical ventilation. Amato et al., in a landmark study, titrated positive end-expiratory pressures (PEEP) levels to higher than the lower inflection point of the pressure-volume curve, with tidal volumes of less than 6 ml/kg and driving pressures of less than 20 cm of H2O in patients with ARDS. On the pressure-controlled mode of ventilator support, they allowed hypercapnia as part of a lung-protective strategy. This strategy resulted in higher PCO2 values compared to the control arm that used a tidal volume of 12 ml/kg (55 vs. 38 mm Hg). However, the lung-protective strategy led to a significantly lower 28-day mortality, less barotrauma, and a higher rate of successful weaning from mechanical ventilation. The use of a low tidal volume strategy was further supported by the ARMA trial and widely accepted as the optimal approach to ventilation in patients with ARDS.

What’s the rationale behind it?

During mechanical ventilation, target the pCO2 levels are conventionally maintained within normal limits (35-45 mmHg). However, the level of ventilator support required maintain normal pCO2 levels can cause damage to the lungs of patients with acute respiratory distress syndrome (ARDS), commonly referred to as ventilator-associated lung injury.

Ventilator-induced lung damage may be attenuated in these patients by adjusting the intensity of mechanical ventilator support. This results in a reduction in alveolar ventilation with an inevitable rise in pCO2 levels. This strategy of deliberate hypoventilation, termed “permissive hypercapnia” has been shown to reduce morbidity and mortality in ARDS and other respiratory diseases requiring mechanical ventilation.

What’s the evidence either in favour of or against it?

As we discussed previously, the benchmark studies of Amato et al. and the ARDS-net study have used the strategy of permissive hypercapnia with improved survival among patients with ARDS. However, hypercapnia may have several adverse effects, including pulmonary hypertension and right ventricular dysfunction, leading to acute cor pulmonale. Hypercapnia may also result in increased susceptibility of tissues to infection. Furthermore, high carbon dioxide levels may impair left ventricular contractility due to intracellular acidosis.

Nin et al. analyzed data from 18,302 patients with ARDS who underwent invasive mechanical ventilation for more than 24 hours or developed ARDS after 24 hours of mechanical ventilation from three international observational studies. On multivariate analysis, they observed a significantly higher mortality among patients with a maximum PaCO2 level of more than 50 mm Hg (defined as “severe” hypercapnia) during the first 48 hours of ventilation compared to those with a maximum PaCO2 level of less than 50 mm Hg. After adjusting for baseline characteristics, an independent association was observed between severe hypercapnia and ICU mortality. Furthermore, the incidence of complications and organ dysfunction, including barotrauma, renal and cardiovascular dysfunction, were more common among hypercapnic patients. ICU mortality was also significantly higher among patients who received a tidal volume of more than 8 ml/kg. 

A registry based study from the Australian and New Zealand Intensive Care Society (ANZICS) database analyzed patients who were mechanically ventilated over a 14-year period. Adult patients who received mechanical ventilation during the first 24 hours of ICU stay were included.  Patients were divided into three groups – with normal pH and PCO2, compensated hypercapnia, and hypercapnic acidosis.

On multivariate analysis, a significantly higher mortality was observed among patients with compensated hypercapnia and hypercapnic acidosis compared to patients with normocapnia and normal pH levels. The mortality difference was unrelated to the P/F ratio. Among patients with compensated hypercapnia, the mortality increased with increasing PCO2 levels to 65 mm Hg; a further rise in PCO2 revealed a trend towards lower mortality. However, in patients with hypercapnic acidosis, the mortality plateaued after a peak PCO2 level of  65 mm Hg. The authors hypothesized that the variable influence of hypercapnia on the arteriolar myogenic tone and consequent modulation of the microcirculation might contribute to this plateau effect.

These studies suggest that the permissive hypercapnia may not be entirely benign, and may worsen clinical outcomes.

Our Recommendations –

  • Low tidal volume strategy with PaCo2 45-50 mmHg
  • Monitor RV with an echo for development of Acute cor pulmonale
  • If PaCO2 remains persistently >50 mmHg &/or patient develops signs of acute cor pulmonale, consider alternate strategies such as prone positioning or ECMO. 
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Dr Swapnil Pawar January 29, 2020

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