Increased physiological dead space in mechanically ventilated COVID-19 patients recovering from severe acute respiratory distress syndrome: a case report

An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally [1, 2]. As of April 29, 2020, the number of total confirmed cases has exceeded 3 million, associated to 207,973 deaths worldwide [1]. Recently, several articles [3‐5] have reported that the early acute respiratory distress syndrome (ARDS) caused by coronavirus disease 2019 (COVID-19) significantly differ from those of ARDS due to other causes, such as mismatch between changes in respiratory mechanics and severity of impaired oxygenation [3], significantly decreased ventilation efficiency [4], and lower lung recruitability [5]. We also found that many mechanically ventilated COVID-19 patients recovering from severe ARDS experienced gradual increases in CO₂ retention and minute ventilation (MV). To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module (COVX module; GE Healthcare, Helsinki, Finland) on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, end-expiratory lung volume (EELV), physiological dead space, ventilatory ratio (VR) [4], and lung mechanics in two COVID-19 patients.

Case 1: A 70-year-old woman (BMI, 21.5 kg/m²) with acute respiratory failure caused by COVID-19 was transferred to Tongji Hospital (Wuhan, China) on February 26, 2020. On admission, she had severe dyspnea (respiratory rate [RR], 40 bpm) and acute hypoxemic respiratory failure (oxygen saturation 45% with oxygen flow 12 L/min) and underwent endotracheal intubation immediately. A tracheotomy was performed 6 days post-admission. She was supported in pressure control mode: inspiratory pressure 15–18 cmH₂O and positive end-expiratory pressure (PEEP) 6–8 cmH₂O. About 14 days post-admission, she experienced a gradual increase in RR (from 25 to 30–40 bpm), tidal volume (VT, from 410 to 480 ml [7.6–9.1 ml/kg PBW]), and MV (from 10 to 12–15 L/min), accompanied by an increased PaCO₂ (from 39 to 47–60 mmHg) and decreased oxygenation (arterial partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2], from 127 to 74–100 mmHg; FiO₂, from 0.5 to 0.7). On day 15, the ventilator was changed to an R860 ventilator with COVX module. The following data were recorded: oxygen consumption (VO₂) 280 ml/min, CO₂ elimination (VCO₂) 175 ml/min; ratio of dead space to VT (VD/VT) 78%, end-tidal carbon dioxide (ETCO₂) 26.1 mmHg, arterial to end-tidal CO₂ difference (P_(a-ET)CO₂) 22.3 mmHg, VR 3.57; EELV 1672 ml; airway resistance (R) 10.8 cmH₂O/L/s, and respiratory system compliance (Cresp) 12.5 ml/cmH₂O. Chest computed tomography (CT) revealed bilateral diffuse ground glass opacity, interstitial fibrosis, traction bronchiectasis, and a small amount of consolidation in the dependent aspects of the lungs on 2 day and 19 day after admission (Fig. 1). Forty days after admission, her lung function still did not recover from sustained hypercapnia in the treatment of Lopinavir/ritonavir, infusion of convalescent plasma, low molecular weight heparin and prone position ventilation, and was transferred to another hospital.

Case 2: A 42-year-old man (BMI, 22.9 kg/m²) diagnosed with COVID-19 was transferred to Tongji Hospital (Wuhan, China) on March 3, 2020. Tracheal intubation and venous-venous extracorporeal membrane oxygenation (ECMO) were performed 25 and 24 days, respectively, before admission due to severe refractory ARDS. ECMO catheters were removed after 14 days of treatment due to a severe blood stream infection. However, ECMO was performed again due to bilateral pneumothorax 8 days before admission. Post-admission, he was treated with antiviral therapy, antibiotic therapy, tracheotomy (1 day post-admission), prone ventilation, and other treatments using our standard protocol. Oxygenation improved gradually, and the ECMO catheter was removed again 19 days post-admission. Over the next week, he showed a gradual increase in MV and hypercapnia. On day 26 post-admission, he was ventilated mechanically in pressure support mode: pressure support 18 cmH₂O, PEEP 3 cmH₂O, FiO₂ 0.3, VT 651 ml (9.2 ml/kg), RR 31 bpm, and MV 17.9 L/min. Arterial blood gas revealed the following: pH 7.463, PaCO₂ 51 mmHg, PaO₂ 80.4 mmHg, HCO₃ 34.9 mmol/L, and PaO2/FiO2 268 mmHg. The following data were recorded using the COVX module: VO₂ 401 ml/min, VCO₂ 292 ml/min; VD/VT 76%, ETCO₂ 33.2 mmHg, P_(a-ET)CO₂ 17.8 mmHg, VR 3.4; EELV 1000 ml; R 7.7 cmH₂O/L/s and Cresp 19.6 ml/cmH₂O. Chest CT showed bilateral ground glass opacity, interstitial fibrosis, and traction bronchiectasis 11 days and 23 days post-admission (Fig. 1). He was disconnected from invasive ventilator and transferred to another hospital for further pulmonary rehabilitation on 38 days post-admission.

We found that the lung tissue of COVID-19 patients recovering from severe ARDS not only reflects the typical characteristics of late-phase ARDS (reduced lung compliance, pulmonary fibrosis, and decreased EELV) but is also associated with a significantly increased dead space (VD/VT 70–80%, VR 3–4), markedly higher than that in patients with severe ARDS due to other reasons [6]. Besides, some COVID-19 patients show an obvious hypermetabolic status even in the recovery period. Therefore, significantly decreased ventilation efficiency and hypermetabolism may explain why these patients experienced more severe respiratory distress and CO₂ retention in the late phase of ARDS.

A remarkably increased physiological dead space may be a prominent pathophysiological feature in mechanically ventilated COVID-19 patients recovering from severe ARDS; however, the underlying mechanism remains unclear. It may be related to significant regional ventilation/perfusion heterogeneity [7] due to loss of lung perfusion regulation and hypoxic vasoconstriction [3], pulmonary microthrombosis [8], and increased anatomical dead space from obvious traction bronchiectasis observed on chest CT.

To reduce the risk of ventilator-induced lung injury with high tidal volume (8–9 ml/kg), we tried to reduce the VT (6–8 ml/kg) and increase the RR to maintain the MV. However, severe hypercapnia (PaCO₂ 98 mmHg, pH 7.10 in case 2) was observed, and the use of sedatives and anesthetic agents had to be increased. These serious consequences are worthy of attention. In these two patients, we set a higher VT (8–9 ml/kg), lower peak airway pressure (< 25 cmH₂O), and low PEEP levels (3–6 cmH₂O) due to low lung recruitability; barotrauma did not occur. Of course, our experience from few patients cannot be extrapolated to all COVID-19 patients, however, this report provides a possible more suitable lung protective ventilation for COVID-19 patients recovering from acute respiratory failure with refractory hypercapnia, which deserved to be further investigated in clinical research.

In conclusion, during the recovery period of ARDS in mechanically ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and VR [4]. Tidal volume (8–9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be considered. In theory, extracorporeal CO₂ removal is a better choice for these patients [9] and will be more beneficial to reduce lung injury while awaiting lung tissue repair; however, further clinical investigations are warranted.