Conservative management of COVID-19 associated hypoxemia
- Alexander Supady1,2,3,
- Philipp M. Lepper4,
- Hendrik Bracht5,6,
- Onnen Moerer7,
- Ralf M. Muellenbach8,
- Guido Michels9,
- Mascha O. Fiedler10,
- Armin Kalenka11,
- Matthias Kochanek12,
- Haitham Mutlak13,
- Guy Danziger4,
- Sebastian Muenz14,
- Dirk Lunz15,
- Sabrina Hoersch16,
- Dawid Staudacher1,2,
- Tobias Wengenmayer1,2 and
- Viviane Zotzmann1,2
- 1Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
- 2Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg im Breisgau, Germany
- 3Heidelberg Institute of Global Health, University of Heidelberg, Freiburg im Breisgau, Germany
- 4Department of Internal Medicine V – Pneumology, Allergology and Critical Care Medicine, Saarland University Medical Center and University of Saarland, Homburg, Germany
- 5Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Baden-Württemberg, Germany
- 6Department of Emergency Medicine, University Hospital Ulm, Baden-Württemberg, Germany
- 7Department of Anaesthesiology, University Medical Centre, Georg-August University Göttingen, Göttingen, Germany
- 8Department of Anaesthesiology and Critical Care Medicine, Campus Kassel of the University of Southampton, Kassel, Germany
- 9Department of Acute and Emergency Care, St. Antonius Hospital Eschweiler, Eschweiler, Germany
- 10Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany
- 11Department of Anaesthesiology and Intensive Care Medicine, Kufstein District Hospital, Kufstein, Austria
- 12First Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf (CIO), University of Cologne, Cologne, Germany
- 13Department of Anaesthesiology, Critical Care Medicine and Pain Medicine, SANA Klinikum Offenbach, Offenbach, Germany
- 14Department of Internal Medicine – Cardiology, Pneumology, Angiology and Intensive Care Medicine, SLK-Hospital Heilbronn, Baden-Württemberg, Germany
- 15Department of Anesthesiology and Intensive Care, University Hospital Regensburg, Regensburg, Germany
- 16Department of Anesthesiology, Intensive Care and Pain Medicine, Saarland University Medical Center and University of Saarland, Homburg, Germany
- Alexander Supady, Medical Center – University of Freiburg, Department of Medicine III (Interdisciplinary Medical Intensive Care), Hugstetter Strasse 55, 79106 Freiburg, Germany. E-mail: alexander.supady{at}universitaets-herzzentrum.de
Abstract
Data presented previously cannot justify a novel approach for treating hypoxic patients with severe COVID-19.
To the editor
With great interest we read the article by Voshaar et al. reporting data from a retrospective analysis of 78 coronavirus disease 2019 (COVID-19) patients treated with or without invasive mechanical ventilation, respectively. The authors conclude that avoiding invasive mechanical ventilation by allowing permissive hypoxemia was superior to current treatment standards and guidelines. Overall mortality in this cohort was 7.7% (6/78), but 50% (4/8) of the patients supported with invasive mechanical ventilation eventually died [1].
We congratulate the authors on this remarkably low mortality of COVID-19 patients treated on an intensive care unit (ICU). We agree that the indication for invasive mechanical ventilation must be made after critical evaluation of treatment alternatives, both in COVID-19 and in other forms of severe respiratory failure. While welcoming additional data that could assist in guiding clinicians in difficult treatment decisions for or against invasive mechanical ventilation at a specific point in time, we are concerned that methodological limitations of this study limit its generalisability. We doubt that the data presented support the authors’ conclusions on invasive mechanical ventilation and prognosis in severe COVID-19. In the following, we will address several concerns about both the study design and data analysis.
First, the study cohort is ill-defined. Basic information describing the patients’ clinical condition and severity of disease (e.g., clinical scores, such as SOFA, APACHE or SAPS II) is missing. This is limiting the possibility to compare findings from this cohort with data from other studies. Given that most of the patients included in this retrospective observation only required oxygen support without nasal high-flow oxygen therapy or mechanical ventilation (53/78, 68%) suggests that these patients were not as severely sick as patients from other intensive care unit (ICU) cohorts [2, 3]. From the data presented, it remains unclear, why most of these patients were treated on an ICU at all.
Second, the authors did not appropriately describe their algorithm for initiation of different respiratory support strategies. The presented “escalation sequence” from “room air” to “invasive mechanical ventilation” does not sufficiently explain triggers or parameters when to progress from one step to another. Most of the patients were treated with oxygen support, but without any type of additional respiratory support. Moreover, patients receiving nasal high-flow oxygen therapy were grouped together with non-invasively ventilated patients, without comprehensive description of the distribution between these treatment strategies. As it does not correspond to the established standard of care, the concept of permissive hypoxemia and the rationale for applying it in this context should be explained and justified in more detail [4].
Third, evaluating hypoxemia alone is insufficient for the description of severe COVID-19 related respiratory failure. Additional data on partial pressure of carbon dioxide and arterial blood pH could help to characterize the kind and degree of respiratory failure in these patients. Furthermore, the authors argue for blood oxygen content to assess tissue hypoxemia. However, in this context, oxygen delivery, considering cardiac output as an additional relevant parameter, would give a better impression of oxygen supply to the tissue and should therefore be reported instead.
Fourth, the authors did not report basic cardiocirculatory parameters, such as vasopressor dosage, nor did they report data on oxygen consumption, such as lactate or central venous saturation (ScvO2), that would further help to better understand severity of disease and discriminate patients. Also, general treatment targets, such as mean arterial pressure and urinary output, should be defined and reported.
Fifth, additional important treatment information is missing. The authors mentioned that prone positioning was applied, however, they did not report information on frequency and duration thereof. Likewise, all patients were treated with a “pneumococcal active antibiotic (ampicillin/sulbactam) in combination with a macrolide”, but no information on potential bacterial super-infection was presented.
Sixth, patients that received invasive mechanical ventilation had seriously elevated troponin and brain natriuretic peptide (BNP) levels suggesting cardiac involvement and global stress, respectively [5]. This finding needs to be explained in order to better understand clinical deterioration and death of these patients. In COVID-19 patients, elevations of troponin and BNP are known to be a strong independent predictor for all-cause mortality [6, 7].
Finally, the sub-group of patients receiving invasive mechanical ventilation (n=8) is too small to allow meaningful inferences and conclusions. Instead, it would have been helpful if the authors related their results and conclusions to relevant findings from thorough assessments of noninvasive mechanical ventilation in much larger cohorts of COVID-19 patients [8, 9].
The authors conclude, that their “data suggest that the lungs recover well from Covid 19 if they are denied the stress of invasive ventilation and over-oxygenation.” Considering the concerns discussed above, this conclusion is not supported by the presented data. In addition, it must be noted that ventilator-induced lung injury and hyperoxemia can occur even with non-invasive mechanical ventilation.
As with all retrospective observational data, causal relationships cannot be assumed and results should be interpreted with caution and in context. Observational data is helpful to generate hypotheses and inform prospective study designs, but changing clinical practice needs to be supported by multiple lines of robust evidence. We believe the data presented here cannot justify a novel approach for treating fragile patients with severe COVID-19.
Footnotes
Authors’ contributions: PML conceptualized the manuscript, AS prepared the first draft. All authors revised and edited the manuscript and added critical content. All authors read and approved the final manuscript.
- Received March 22, 2021.
- Accepted March 30, 2021.
- Copyright ©The authors 2021
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