Phenotypes of COVID-19-associated dysautonomia in patients requiring veno-venous extracorporeal membrane oxygenation

Background. Patients with novel coronavirus infection (COVID-19) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) are typically prone to hemodynamic disorders of various severity. Tachycardia, increased cardiac output, or arterial hypotension affect the effectiveness of VV-ECMO. One of the possible causes of hemodynamic disorders leading to ineffective VV-ECMO may be dysautonomia (DA), which refers to an imbalance of sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). The development of DA in various critical conditions was described previously. Dysautonomia also develops in COVID-19 (COVID-19-associated DA), but it was studied only in stable non-ICU patients. The presented study focuses on COVID-19-associated DA in critical COVID-19 patients requiring VV-ECMO support.

The study was aimed at determining COVID-19-associated DA phenotypes, their impact on VV-ECMO effectiveness and disease outcomes.

Materials and methods. The study included 20 patients: 12 (60%) females, 8 (40%) males. The patients had an average age of 55 years. All the patients underwent 24-hour Holter monitoring with spectral analysis of heart rate variability (HRV) assessing low-frequency component of the spectrum (LF), the high-frequency component of the spectrum (HF), the LF/HF ratio on days 1, 3, and 5 of VV-ECMO. Diagnostic criteria for COVID-19-associated DA was a decrease in LF/HF < 2.28 or an increase in LF/HF > 6.94. The diagnostic criteria of predominant tone of sympathetic nervous system (sympathetic tone) was an increase in LF/HF > 6.94, while a decrease in LF/HF < 2.28 indicated predominant parasympathetic tone. Low sympathetic tone was determined by a decrease in LF < 15%, and an increase in LF > 40%. Low parasympathetic tone was determined by a decrease in HF < 15%, and an increase in HF > 25%. The criteria used were based on the results of previous studies.

The following parameters were registered in the study population: VV-ECMO weaning, duration of respiratory and VV-ECMO support, length of stay in the intensive care unit (ICU) and in hospital, and disease outcomes.

Results. COVID-19-associated DA was diagnosed in all the patients. LF/HF median value was 0.1. HRV spectrum parameters changed significantly over time: on day 5 of VV-ECMO support LF and HF values significantly decreased. The patients were divided into three groups according to the DA phenotype: group 1 (n = 4 [20%]) with normal sympathetic tone and high parasympathetic tone (nShP phenotype); group 2 (n = 14 [70%]) with low sympathetic tone and high parasympathetic tone (lShP phenotype); group 3 (n = 2 [10%]) with low sympathetic tone and normal parasympathetic tone (lSnP phenotype). The latter group was excluded from further statistical analysis due to the small sample size. In group 2, the mean HR was significantly higher compared with group 1. In group 1, VV-ECMO weaning was successful in 50% of cases, whereas in group 2 it was successful in 7.2% (p = 0.04).

Conclusions. To determine a dysautonomia phenotype, it is necessary to continuously monitor DA status in COVID-19 patients during VV-ECMO. Tachycardia in COVID-19 patients during VV-ECMO does not exclude the ANS imbalance with a significant predominance of parasympathetic tone over the sympathetic tone. It is this COVID-19-associated DA phenotype that is significantly associated with the unfavorable outcomes.