{'fraction_non_alphanumeric': 0.0326163610719323, 'fraction_numerical': 0.01304654442877292, 'mean_word_length': 5.374157303370787, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Respiratory acidosis and acute respiratory distress syndrome: time to trade in a bull market?

Mechanical ventilation can induce or exacerbate lung injury (1). A low tidal volume strategy limiting alveolar overdistention has been shown to improve outcome in patients with acute respiratory distress syndrome (ARDS) (2, 3). Experimental data not yet clinically confirmed suggest that positive endexpiratory pressure may also help reduce ventilator-induced lung injury (VILI) by limiting tidal excursion and/or cyclic opening and collapse (4, 5). The low tidal volume and limited tidal pressure excursion inherent to such approach may result in alveolar hypoventilation and respiratory acidosis (RA), especially in patients with the largest physiologic deadspace and risk of death (6). Hypercapnia and respiratory acidosis are generally viewed as the consequences of lung-protective strategies that are to be tolerated (permissive hypercapnia), limited (increased respiratory rate or tracheal gas insufflation), or partially treated (infusion of buffer). More recently, inhaled carbon dioxide (therapeutic hypercapnia) was found in experimental models to limit various types of lung injury including VILI (7, 8). The optimal bedside approach is still debated. In theory, balancing the side effects of RA with the risks associated with the specific ventilatory settings (tidal volume or peak alveolar pressure, positive end-expiratory pressure, and ventilatory rate) used to achieve a given alveolar ventilation and PaCO2 is of paramount importance. One also needs to consider the following: a) the presence of comorbidity affecting the tolerance to RA (e.g., the myocardial function, the coronary circulation reserve, and the capacity of the central nervous system to compensate for a change in intracranial pressure); b) the severity and cause of ARDS, because the underlying injury severity may increase the risk of VILI associated with a given ventilatory strategy (9) and the effects of RA may vary with the underlying cause of lung injury (10); and c) the additional mechanical stress associated with the strategy used to maintain or restore normocapnia. Clearly, an optimal approach to RA needs to be tailored to each patient’s characteristics. Those who strongly believe in standardized care will have to “hold their breath” for the unlikely occurrence of uniform strategy applicable to all ARDS patients (excluding banning excessive tidal volume) anytime soon. For the foreseeable future, physicians will continue to be forced to make complex decisions regarding RA for individual ARDS patients with many unanswered questions. What have we learned regarding RA and mechanical ventilation that might help making such decision? Experimentally, RA has the potential to limit the increased permeability (7, 11) and inflammation induced by alveolar overdistention (8). Possible pathways for such effects may involve nuclear factorB (12), nitric oxide (7), apoptosis (13), and neutrophil “function” (14). Interestingly, no such protective effect against ventilation at low positive end-expiratory pressure (atelectrauma) appears to be afforded by RA (15). There is growing evidence that RA may be a double-edged weapon that limits the permeability alteration and impairs membrane reselling associated with overstretch (16). Additional considerations relevant to the dual protective and detrimental effects of RA include the method used to induce respiratory acidosis (inhaled CO2 vs. hypoventilation), the inspired oxygen concentration, the interaction between carbon dioxide and NO, and the lung injury model (17–19). For instance, CO2 inhalation (7) and nitric oxide production inhibition (19) appear to be protective against VILI. In contrast, RA induced by hypoventilation may be detrimental and inhaled nitric oxide may be protective in the setting of lipopolysaccharide-induced lung injury (20). In the absence of contraindications, RA appears generally well tolerated, particularly by otherwise healthy patients such as those with asthma (21). When necessary, hypoventilation and permissive hypercapnia to help limit air trapping, barotrauma, and hypotension appear to have been instrumental in reducing the mortality rate of asthmatic ventilated patients (21). At the time, this new ventilatory paradigm (22) shifted the emphasis away from attempting to normalize gas exchange toward limiting adverse effects of mechanical ventilation to buy time for the underlying condition to improve. In the latter strategy, any blood gas that does not compromise a full recovery is theoretically acceptable. A similar approach in patients with ARDS was proposed in 1994, when Hickling and colleagues (23) reported a strikingly low mortality rate (26%) using low tidal volume and tolerating a mean maximum PaCO2 of 66 mm Hg (range 38–158) and a mean arterial pH of 7.23 (range 6.79– 7.45). The relative contribution of CO2 and low tidal volume to outcome is a key question; however, it was not addressed in the latter and all subsequent randomized trials that tested the low tidal volume hypothesis. In the current issue of Critical Care Medicine, Dr. Kregenow and colleagues (24) report the results of a multivariate logistic regression that tested the hypothesis that RA was associated with a lower mortality rate. They used the data from the low vs. high tidal volume ARDSnet trial (3). Their hypothesis was confirmed only in the patients ventilated with the larger tidal volume but not in those ventilated with lower one. This study suffers from the weaknesses inherent of such approach: No cause-effect relationship can be inferred, and the mechanisms that *See also p. 1.