Rebuttal from Gerard F. Curley, John G. Laffey and Brian P. Kavanagh

Authors

  • Gerard F. Curley,

    1. Department of Anesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada
    2. Department of Anesthesia, University of Toronto, Ontario, Canada
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  • John G. Laffey,

    1. Department of Anesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada
    2. Department of Anesthesia, University of Toronto, Ontario, Canada
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  • Brian P. Kavanagh

    1. Department of Anesthesia, University of Toronto, Ontario, Canada
    2. Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Email: brian.kavanagh@utoronto.ca

Beitler et al.'s (2013) review of the benefits and mechanisms of avoiding high tidal volume are right on the mark. In addition, they provide a sound biophysical basis for our concern about increasing respiratory rate to offset hypercapnic acidosis (HCA).

However, the parallels drawn from other clinical contexts are problematic. For example, the trial of intravenous salbutamol for acute lung injury – stopped early due to harm – is a poor choice. Key concerns regarding salbutamol in that study are rare with moderate hypercapnia such as arrhythmia (Amato et al. 1998; Stewart et al. 1998; Brower et al. 1999), lactic acidosis (hypercapnia reduces it) (Higgins et al. 2009), and impaired oxygen supply–demand balance (hypercapnia improves it) (Wang et al. 2008).

Likewise, HCA may certainly worsen pulmonary hypertension, and potentially the outcome; however, it attenuates a key antecedent of pulmonary hypertension, namely oxidant stress (Kantores et al. 2006). Elevated pulmonary vascular pressure in acute respiratory distress syndrome (ARDS) appears not to worsen mortality during low tidal volume ventilation (Osman et al. 2009). Indeed, HCA can augment ventilation–perfusion matching and thereby minimize the need for additional (harmful) ventilatory support (Ketabchi et al. 2009).

The sedation issue is confounded as reports exist of HCA increasing (Stewart et al. 1998) or not increasing (Brower et al. 1999) sedative use; in the absence of protocolized sedation the evidence remains deficient. Moreover, the important patient–ventilator dyssynchrony mentioned by Beitler et al. may be due to inappropriate ventilator volume or flow, rather than hypercapnia per se.

Immunosuppression from HCA is definitely a concern, especially in sepsis. However, the host response to infection may also contribute to organ injury. It is reassuring that with appropriate antibiotic use HCA does not increase bacterial load or organ injury in experimental pneumonia (Chonghaile et al. 2008); this parallels the conventional use of indicated immunosuppressive therapy in critically ill patients where the risk–benefit ratio is understood and surveillance undertaken.

Should HCA during low tidal volume ventilation be treated with buffering agents? Buffering may ablate the protective effects of HCA (Laffey et al. 2000); indeed, while tris-hydroxymethyl amino-methane (THAM) may be preferable to sodium bicarbonate (less intracellular acidosis), the evidence from Dr Hubmayr's laboratory (Caples et al. 2009) indicates that this approach may be harmful.

In summary, hypercapnia has beneficial and deleterious effects, depending on its level, timing and context. This is true of most therapies. The cumulative evidence suggests that appropriate use of permissive hypercapnia in ARDS might eventually prove beneficial.

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Acknowledgements

J. G. Laffey is supported by a Merit award and G. F. Curley by a Clinician Scientist Transition award, from the Department of Anesthesia at the University of Toronto.

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