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The wisdom of organizing illness into clinical syndromes—sepsis, ARDS, and the like—has been debated for at least 50 years, perhaps longer.1,2 The utility comes from a syndrome’s ability to facilitate the recognition or understanding of an important common element among the people who receive the label.3 The “lumpers,” being in favor of syndromes as a paradigm, note the promise of more reliable clinical recognition, efficient enrollment into studies, and optimization of care processes. The “splitters,” taking the opposite position, emphasize the peril of grouping patients with different pathophysiology, different natural histories of disease, and differing responses to treatment. If the average outcome poorly represents how individuals will respond, both individual care and the efficiency of trials suffer.
Hypercapnic respiratory failure is the syndrome that occurs when alveolar ventilation is insufficient to match metabolic demand. Is the “syndrome paradigm” the right way for us to improve how we treat these patients? Or would efforts be better spent focusing on individual diseases? Comparison to where other syndrome-based research has excelled or struggled might provide guidance.
The heterogeneity of patients labeled as having ARDS or sepsis is one proposal for why few trials studying therapies for those conditions have shown replicable benefits.4 A diverse range of pathologies can lead to hypercapnia. Permutations of physiologic derangements limiting the maximal sustainable ventilation (unfavorable respiratory system loads, muscle weakness, mechanical disadvantage, unstable ventilatory control) and those leading to a large ventilation requirement (ventilatory inefficiency, elevated metabolic rate) contribute to hypercapnia in differing degrees in different diseases.5 Will most patients with hypercapnic respiratory failure respond similarly to a proposed management strategy? The demonstrated benefit of noninvasive ventilation (NIV) in COPD is contingent on selecting only specific patients (that remain hypercapnic after 2–4 weeks of stability) and applying a specific strategy (high …
Correspondence: Brian W Locke MD. E-mail: brian.locke{at}hsc.utah.edu
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