Permissive Hypercapnia in ARDS

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.