key: cord-0722613-zi9ebc8v
authors: Ottestad, William; Søvik, Signe
title: COVID-19 patients with respiratory failure: what can we learn from aviation medicine?
date: 2020-04-18
journal: Br J Anaesth
DOI: 10.1016/j.bja.2020.04.012
sha: f9aac076141cf3b5a40b2453472f80128556c333
doc_id: 722613
cord_uid: zi9ebc8v

nan

atypical form of acute respiratory distress syndrome. 1 Although anecdotal, a common clinical pattern has emerged, with a remarkable discrepancy between relatively well preserved lung compliance and a severely compromised pulmonary gas exchange, leading to grave hypoxaemia yet without proportional signs of respiratory distress. The compensatory ventilatory response to hypoxaemia, increased minute ventilation, may lead to extreme hypocapnia. Carbon dioxide (CO 2 ) diffuses through tissues about 20 times more rapidly than does oxygen (O 2 ), and these properties likely underlie the disproportional pulmonary exchange of CO 2 and O 2 in these patients. The pathoanatomical and pathophysiological basis for respiratory failure in COVID-19 is yet undetermined, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. 2 Varying degrees of atelectasis and consolidation likely contribute.

Experiments in hypobaric chambers have revealed that hypocapnic hypoxia is not usually accompanied by air hunger; instead a paradoxical feeling of calm and well-being may result. This phenomenon has been coined "silent hypoxia". End-tidal CO 2 values in the 1.4-2.0 kPa range have been reported in COVID-19 patients, but apart from a rapid respiratory rate the clinical presentation in these patients can be misleading. We have observed patients with extreme hypoxaemia showing little distress; rather they tend to be impassive, cooperative and haemodynamically stable. However, sudden and rapid respiratory decompensation may occur. This particular clinical presentation in COVID-19 patients contrasts with our previous experience with critically ill patients in respiratory failure in which patients with decompensated heart failure, sepsis, or massive pulmonary embolism tend to present with air hunger, dyspnoea, distress, arterial hypotension, and isocapnic or hypercapnic hypoxia.

The physiological hallmarks of hypocapnic hypoxia have been studied extensively in aviation medicine. 3 Decompression to high altitude causes severe hypoxaemia, which triggers the carotid chemoreceptors and sparks a brisk respiratory response with ensuing hypocapnia. The respiratory alkalosis shifts the oxyhaemoglobin dissociation curve to the left, thereby increasing haemoglobin's oxygen affinity, evident from a decrease in the P 50 value and an increase in arterial oxygen saturation (S a O 2 ). 4 Additionally, the alveolar gas equation predicts that decreased alveolar CO 2 tension (P A CO 2 ) will result in a corresponding increase in alveolar oxygen tension (P A O 2 ).

Combined, these two mechanisms will increase S a O 2 in hypocapnic hypoxia compared to an isocapnic or hypercapnic hypoxic state. We speculate that most clinicians' intuitive understanding of the effect size produced by these mechanisms for a given change in P a CO 2 may be limited.

The effects of hypocapnia on S a O 2 can be illustrated with data from a recent hypobaric chamber experiment. In a simulated high-altitude parachute jump from 30.000 ft, nine volunteers from the Norwegian Special Operations Command underwent repeated blood gas testing while breathing air at different ambient pressures. 5 Extreme hypocapnic hypoxia in patients with respiratory failure has previously been relatively unusual, therefore this presentation challenges our intuitive thinking and clinical pattern recognition. The physiology of hypocapnic hypoxia has implications for how we interpret physiological parameters. Instinctively, we judge an S p O 2 value of 93% as fair. However, without knowledge of the accompanying P a CO 2 value it is impossible to infer from S p O 2 the degree of hypoxaemia and consequently the severity of the respiratory failure.

COVID-19 patients have a median reported duration from illness onset to ICU admission of 12 days 1 , and they can deteriorate quickly. Ensuring timely hospital admission can therefore be challenging. These patients are evaluated by general practitioners, often by telephone due to quarantine rules, or by paramedics or emergency physicians in a pre-hospital context. To assess the risk of imminent respiratory failure, clinical evaluation should give emphasis to respiratory rate, work of breathing, use of accessory musculature, and skin perfusion. Pulse oximetry readings should be interpreted in the light of P a CO 2 values or while acknowledging the absence of this important information. Although arterial-alveolar difference in PCO 2 increases during low cardiac output states and increased dead space ventilation, end-tidal CO 2 values have been reported to correlate well with P a CO 2 in non-intubated patients, especially during hypocapnia 6 . End-tidal CO 2 can be easily measured in a pre-hospital setting.

In COVID-19 patients, a low end-tidal CO 2 should alert the physician that respiratory failure is evolving and that decompensation might be imminent. If ventilatory support is instituted, anaesthesiologists, emergency physicians and intensivists should be aware of the need to sustain a high ventilatory minute volume. In the case of intubation one should consider the danger of apnoea during induction of anaesthesia. In marginal patients with severe hypocapnic hypoxia, a rise in P a CO 2 will lead to a right shift of the oxyhaemoglobin dissociation curve, resulting in an abrupt fall in S a O 2 and a risk of circulatory collapse.

The clinical presentation and pathophysiology of the COVID-19 patient challenges our notion of how respiratory failure in critically ill patients unfolds. We must adapt to a constantly changing situation with a rapidly expanding evidence base. Awaiting reliable data, we have to integrate experience with our understanding of physiology to make rational clinical decisions.

The authors have no conflicts of interest to disclose.

Relation between arterial oxygen saturations (S a O 2 ) and arterial partial pressures of carbon dioxide (P a CO 2 ) in eight volunteers breathing air in a hypobaric chamber at ambient pressure 42.1 kPa, corresponding to a pressure altitude of ~ 22,000 ft. 5 Inspiratory oxygen pressure is 7.5 kPa. The model predicts that an increase in P a CO 2 from 2.5 to 4.5 kPa would decrease S a O 2 from 87% to 50%. R 2 = 0.88, p< 0.001.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer

The oxygen dissociation curve: quantifying the shift

Acute hypoxia in a simulated high-altitude airdrop scenario due to oxygen system failure

Correlation of end-tidal CO 2 measurements to arterial P a CO 2 in nonintubated patients