key: cord-285896-lb8toc1m
authors: Beurton, Alexandra; Haudebourg, Luc; Simon-Tillaux, Noémie; Demoule, Alexandre; Dres, Martin
title: Limiting positive end-expiratory pressure to protect renal function in SARS-CoV-2 critically ill patients
date: 2020-07-10
journal: J Crit Care
DOI: 10.1016/j.jcrc.2020.07.008
sha: 
doc_id: 285896
cord_uid: lb8toc1m

nan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related pneumonia is a risk factor for acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) [1, 2] . While the mechanisms of AKI in this context are not yet elucidated, it is likely that providing a lung protective mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) may worsen renal function [2] [3] [4] [5] . Accordingly, strategies of PEEP titration [6] and hemodynamic management in SARS-CoV-2 related ARDS are still open to discussion.

Herein, we report our experience in SARS-CoV-2 critically ill patients before and after having modified our practices in the view of the high occurrence of AKI that needed renal replacement therapy (RRT) in the first cases we managed. Our hypothesis was that limiting the level of PEEP (< 12 cmH 2 O) while targeting upward mean arterial pressure (> 75 mmHg) during the first 48 hours after the intubation would decrease the need for RRT.

During "period 1" (between 04 and 15 March 2020), all mechanically ventilated patients with confirmed SARS-CoV-2 admitted to our intensive care unit received volume-controlled ventilation with a tidal volume of 6 ml/kg of ideal body weight and PEEP stepwise increased to reach a plateau pressure below 28 cmH 2 O. A conservative fluid strategy (i.e. fluid expansion based on bedside evaluation of the cardiac preload dependence) was applied and norepinephrine infusion targeted a mean arterial pressure > 65 mmHg. During "period 2" (from 16 March to 06 April 2020), the following changes were applied: 1) PEEP was limited to 10-12 cmH 2 O; 2) liberal fluid strategy was applied (no systematic preload dependence evaluation) and 3) norepinephrine was administrated to achieve a mean arterial pressure > 75 mmHg. We collected baseline patient's characteristics, ventilatory and hemodynamic management, daily clinical and biological data and the need J o u r n a l P r e -p r o o f for RRT until day 14. The Lung Injury Score (so called Murray score), which is a four-category scale including: 1, chest roentgenogram score; 2, hypoxemia score; 3, PEEP score; 4, respiratory system compliance score was also collected at admission [7] . During the two periods, the management of RRT was similar and followed our local guidelines based on the delayed RRT strategy group of the AKIKI study [8] . The primary endpoint was the proportion of patients requiring RRT at day 14. The statistical analysis compared patient's baseline characteristics, therapeutic management and the proportion of patients with AKI. Our local ethics committee approved the study (CER Sorbonne University, N°2020 -CER-2020-32).

Patients or their family gave their oral consent.

Results. Seventy-three patients were included, 20 during "period 1" and 53 during "period 2". Baseline characteristics were not different between periods (Table 1) Figure 1 ). The peak airway pressure was similar in the two groups (Table 1 ). Despite a lower PEEP level during "period 2", the Lung Injury Score was similar between the two groups, as well as the mortality (Table 1 ).

Discussion. Our findings suggest that changing our practices was associated with a decreased need for RRT and a lower proportion of patients with AKI KDIGO 3. This might not be a causal relationship and further confirmation is warranted. Several factors may contribute to AKI onset, as comorbidities such as hypertension or diabetes mellitus. These factors are well-known factors of renal vulnerability and have been recently identified as risk factors for AKI in patients with ARDS [2, 10] . In patients with SARS-CoV-2 related ARDS, impairment of gas exchange and severe hypoxemia has been recognized as others risk factors [2] . The association between PEEP and AKI has been suggested in physiological studies [2, 4, 5] but recently, Panitchone et al. have suggested an association between peak airway pressure and AKI [10] . This association was not found in our patients. However, in the early phase of SARS-CoV-2 related ARDS, pulmonary mechanics may be different from traditional ARDS, with different phenotypes characterized by low lung recruitability, normal compliance and without need for very high PEEP or even deleterious effects of the latter [6] . The timeline of AKI onset is another issue. In our patients, we have found that AKI occurred most commonly within 24 hours of intubation, as Hirsch et al. have suggested [11] .

The main limitation of our study is the retrospective design that limits the causal relationship of our findings. In addition, the significant proportion (20%) of patients with extra-corporeal membrane oxygenation could have influence our findings but this case mix was inherent to our activity as expert-center. Nevertheless, our experience suggests the existence of a critical cross-talk between lungs and kidney function [2, 12] in SARS-CoV-2 critically ill patients. Careful monitoring of lung and kidney interaction is required in these patients. High levels of PEEP may not be required in the early phase of SARS-CoV-2 related ARDS.

J o u r n a l P r e -p r o o f

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19

Acute kidney injury in critically ill patients with COVID-19

Renal hemodynamic and functional effect of PEEP ventilation in human renal transplantations

Effect of PEEP Ventilation on Renal Function, Plasma Renin, Aldosterone, Neurophysins and Urinary ADH, and Prostaglandins

Lung-Kidney Cross-Talk in the Critically Ill Patient

COVID-19 pneumonia: different respiratory treatments for different phenotypes?

An Expanded Definition of the Adult Respiratory Distress Syndrome

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit

Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary

Factors associated with acute kidney injury in acute respiratory distress syndrome. Ann Intensive Care

Acute kidney injury in patients hospitalized with COVID-19

Understanding the kidney during acute respiratory failure