key: cord-275012-fkawgh0e
authors: Tavazzi, Guido; Marco, Pozzi; Mongodi, Silvia; Dammassa, Valentino; Romito, Giovanni; Mojoli, Francesco
title: Inhaled nitric oxide in patients admitted to intensive care unit with COVID-19 pneumonia
date: 2020-08-17
journal: Crit Care
DOI: 10.1186/s13054-020-03222-9
sha: 
doc_id: 275012
cord_uid: fkawgh0e

nan

old; 93% male). All patients required iNO for refractory hypoxaemia of whom 4 (25%) had also superimposed RV dysfunction, in 1 case associated with pulmonary embolism. The iNO dosage was 25 [20-30] parts per million (ppm).

Respiratory parameters at t 0 and t 1 are shown in Table 1 . Overall, iNO did not improve oxygenation in our population. Only 4 (25%) patients were responders, of whom 3 iNO is a free radical gas that diffuses across the alveolar-capillary membrane into the subjacent smooth muscle of pulmonary vessels enhancing endotheliumdependent vasorelaxation and improving oxygenation by increasing blood flow to ventilated lung units [3] . In previous studies, iNO was effective in improving PaO 2 /FiO 2 and oxygenation index, although it failed in reversing acute lung injury, reducing mechanical ventilation days and mortality [4] .

In our population, the improvement of oxygenation in responders was probably magnified by an iNO-induced decrease of RV afterload, enhancing cardiac output and finally leading to an increase of mixed venous oxygen saturation.

Although the reason why patients with refractory hypoxaemia without RV dysfunction were not responder is yet to be determined, some speculation can be done. Severe endothelial injury with cytoplasmic vacuolization and cell detachment in pulmonary middle-small arteries can make the pulmonary vessels less reactive to iNO stimulation [1, 5, 6] . This could also explain the loss of hypoxic vasoconstriction and lung perfusion regulation. However, whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus, part of the ARDS pathophysiology or the intertwine of both is still undetermined. Moreover, prone position and iNO were used in refractory hypoxaemia as an escalating treatment strategy. Therefore, a positive response to the prone position may have precluded the enrolment in our study of patients that could positively respond to iNO.

Overall, iNO did not improve oxygenation in COVID-19 patients with refractory hypoxaemia, when administered as a rescue treatment after prone position. A subgroup of patients with RV dysfunction was better iNO responders probably due to the haemodynamic improvement associated with RV unloading.

The word count of our manuscript is just beyond the limit suggested by the editorial rules as we felt that the fluency and completeness would be sacrificed in further shorten the text. However, we are willing to cut some part if strongly advised by the editorial office. 

Management of COVID-19 respiratory distress. JAMA. 2020. Online ahead of print

Update in management of severe hypoxemic respiratory failure

Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential

Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults

Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection

Endothelial cell infection and endotheliitis in COVID-19

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We thank all the nurses and physicians involved in the management of such epidemics ( 

All authors contributed equally to the data collection and redaction, writing and final revision before submission of the paper. The author(s) read and approved the final manuscript.

No funding were received for the submitted work.

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Ethics approval and consent to participate Informed consent was collected following the ad hoc procedures defined by the local Ethics Committee of Fondazione Policlinico San Matteo IRCCS for the COVID-19 pandemic.Competing interests FM received fees for lectures from GE Healthcare, Hamilton Medical, SEDA SpA, outside the present work. SM received fees for lectures from GE Healthcare, outside the present work. GT received fees for lectures by GE Healthcare, outside the present work. MP, VD and GR have nothing to disclose.Received: 22 July 2020 Accepted: 3 August 2020