Acute respiratory distress syndrome

Dear Editor,

Wick et al [1] brilliantly update the knowledge on acute respiratory distress syndrome (ARDS). Progress over the last 50 years was sluggish, with some achieving a 16% 28-day mortality [2], while most achieve a 30-50 % mortality. The present state-of-the-art uses early controlled mechanical-mandatory ventilation (CMV): mechanical ventilator-induced inflammation adds on disease-induced inflammation [1], with a high toll. Therefore, refined CMV combined eventually with immunotherapy to address dis-ease-induced inflammation [1], leads to high mortality.

At variance with the state-of-the-art, treatment should be considered entirely on a non-invasive basis to start with. CMV is a backup only when large tidal volume (Vt) is uncon-trolled upon spontaneous breathing (SB). The tenet is that CO2 excretion and O2 diffu-sion are being achievable without intubation and CMV. Indeed, ventilatory failure en-compasses two entirely different processes when decompensated chronic obstructive pulmonary disease (COPD) is opposed to ARDS:

First, COPD. The extraction of CO2 by the ventilatory pump is the main issue, with CO2 production a function of the temperature of the patient. Therapy of decompensated COPD is obvious: CMV extracting CO2.

Second, ARDS. CO2 is low with high tidal volume (Vt) [3]. The ventilatory pump is intact, with a caveat for sepsis [4]. CMV becomes unnecessary. But O2 diffusion is now the issue (altered VA/Q: low: atelectasis, alveolar flooding; high, I.e., micro or macro-thrombi as in Covid-19). Treatment is difficult [1]: a) CMV causes mechanical inflamma-tion b) a large Vt under SB generates mechanical self-induced lung injury worsening dis-ease-induced inflammation.

ARDS treatment addresses temperature, agitation, cardiac output, microcirculation and local pH, inflammation, positioning, systemic pH, PaCO2 and PaO2. If only CO2 and O2 are considered:

a) lowering the temperature [5] to about 35°C reduces VCO2 (minus 8-10% per °C) [6]. This lowers Vt and/or respiratory rate. Low flow veno-venous CO2 removal handles VCO2, with little use for CMV. Low normothermia avoids coagulation and immunological disorders.

b) arterial oxygenation is achieved with very high O2 flow (VHFN, 120 L.min-1 [7]), com-bined with high flow O2 mask (30 L.min-1) avoiding O2 dilution through the mouth. O2 greater than or equal to 150 L.min-1 achieves relatively high PEEP (7-16 cm H2O) and acceptable arterial oxygenation despite very high intrapulmonary shunting (80 mm Hg less than PaO2 less than 120 mm Hg, i.e., no permissive hypoxemia). This buys time for self-healing. Helmet non-invasive ventilation (NIV) is a backup. Additionally, the abundant vascular drainage via the hemorrhoidal plexuses may be considered. The blood returning to the lung may be oxygenated using rectal insufflation of O2 with continuous re-aspiration of the left colon. A modified “enteral ventilation”[8] is combined with lowered intraabdominal pressure (e.g., appropriate exoneration). If normothermia or VHFN achieve normocapnia or appropriate oxy-genation, CO2 removal or enteral oxygenation are unnecessary.

Prolonged VHFN/NIV requires addressing anxiety and agitation, without resorting to propofol, midazolam and fentanyl. High dose alpha-2 agonists (clonidine, dexme-detomidine: 2 or 1.5 microg.kg-1.h-1 respectively) address temperature, agitation and patient’s comfort (with haloperidol if sedation is inadequate [9]) without respiratory depression. Indeed, general anesthetics and opioids generate inflammation. By contrast, alpha-2 agonists normalize sympathetic hyperactivity and lower inflammation of relevance with hyperinflammation. Cardiac output is normalized [10] before high PEEP (VHFN) and alpha-2 agonists.

This bundle (low normothermia, VHFN, veno-venous ECMO, enteral oxygenation) requires feasibility and validation [11]. The emphasis is on mechanical and disease-induced inflammation, according to ARDS phenotypes. CMV remains only a rescue therapy, e.g. in the setting of major abdominal sepsis. This last line of defense is used only when “absolutely necessary” [12] avoiding a high toll.
 
1. Wick KW, Ware, L.B, Matthay M.A. Acute respiratory distress syndrome. British Medical Journal 2024;369:e076612.
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