key: cord-0899764-9srclxkv
authors: Scarpino, Maenia; Bonizzoli, Manuela; Lazzeri, Chiara; Lanzo, Giovanni; Lolli, Francesco; Ciapetti, Marco; Hakiki, Bahia; Grippo, Antonello; Peris, Adriano; Ammannati, Andrea; Baldanzi, Fabrizio; Bastianelli, Maria; Bighellini, Annamaria; Boccardi, Cristina; Carrai, Riccardo; Cassardo, Annalisa; Cossu, Cesarina; Gabbanini, Simonetta; Ielapi, Carmela; Martinelli, Cristiana; Masi, Giulia; Mei, Cristina; Troiano, Simone
title: Electrodiagnostic findings in patients with non‐COVID‐19‐ and COVID‐19‐related acute respiratory distress syndrome
date: 2021-04-22
journal: Acta Neurol Scand
DOI: 10.1111/ane.13433
sha: b1def977762068ae26d20ae9446911deffc8d498
doc_id: 899764
cord_uid: 9srclxkv

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID‐19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID‐19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single‐centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016‐June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID‐19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID‐19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

At the end of 2019, many pneumonia cases occurred in Wuhan, China, which later spread to all over the world. This outbreak was caused by a new virus of Corona (CoV) called COVID-19. 1 for different reasons. 12 In particular, this neurological disease has already been described in patients with ARDS of different aetiologies, including influenza A (H1N1) or bacterial infections, 13,14 despite confounding factors mainly concerning mechanisms underlying CIPNM onset. [14] [15] [16] Recent evidence 5, 9 suggested that critically ill patients affected by COVID-19 may differ from typical ARDS patients in ICU exposures associated with ICUAW and CIPNM. 17 There are only few studies 8, 9, [18] [19] [20] in which CIPNM presence was investigated with instrumental (electroneurography -ENG and electromyographic -EMG) tests which allowed a quantitative approach and, at the same time, were not subject to confounding factors, often present in critically ill patients.

In addition, to the best of our knowledge, there is still no evidence of literature regarding an instrumental comparison of the detection of CIPNM in ARDS patients of different aetiologies, including COVID-19.

Given these limitations, we compared patients admitted to the ICU for ARDS of different aetiologies on whom an ENG/EMG evaluation for the detection of the CIPNM was performed, to patients with ARDS from COVID-19 infection. The aim was to evaluate if there were any differences between these two groups of ARDS patients, in terms of frequency of CINPM and outcome at discharge from the ICU. 

Patients were managed according to local clinical practice; in particular, the standard therapeutical approach to ARDS, including lung protective ventilation, was applied. 21, 22 All ARDS patients were treated with neuromuscular blockade, for at least 48 h after starting mechanical ventilation, and with light sedation (propofol 1-2 mg/Kg/h). Low doses of systemic steroids were also used, especially in patients with ARDS due to COVID-19

ARDS, CIPNM, COVID-19, ENG/EMG, neurological manifestations infection. 23 Antibiotics and/or antiretrovirals were administered according to ARDS aetiology.

ECMO treatment was started on the basis of the Italian Ministry of Health criteria. 24 Conditions of severe hypoxia or hypercapnia, exceeding the limit values for protective ventilation (tidal volume less than 6 ml/kg and plateau pressure of 30 cm H2O), represented the criteria for proceeding with the treatment. 25, 26 Early physiotherapy was performed in all patients according to local protocol. 27 The evaluation of osteotendinous reflexes in bilateral upper and lower limbs was also considered.

We collected the following biochemical parameters: creatine phosphokinase (CPK) and lactic dehydrogenase (LDH), using colorimetric method, as muscle damage indices and the mean morning glycaemia. Neurography values were referenced to upper and lower limits of normality, which were calculated from 80 normal subjects in our laboratories. 30 The presence of CIPNM was defined by a low or very low amplitude of CMAP and, in some cases, of SNAP on ENG exam with normal or mildly reduced nerve conduction velocities, associated with myopathic features on needle electromyography. 31 Neurophysiological evaluation was performed at least 24 h after the last administration of neuromuscular blockers.

Qualitative variables were presented as frequency (percentage), and quantitative variables are provided as mean (standard deviation, SD) or median (interquartile range, IQR). We used the Chi-square test or

Fisher's exact test (for qualitative variables) and Student's t test or

Mann-Whitney U test (for quantitative variables) to study the different variables in the patient cohorts. For all the tests, we considered p-values <.05 as statistically significant.

As no guidelines have indicated a unique severity EMG criterion of CMAP and/or SNAP amplitude reduction in the instrumental diagnosis of CIPNM, we employed a cluster analysis (k-means algorithm in SPSS, ver. 26) to dichotomize our patients, using the whole ENG results. They were segmented as normal/good results in one cluster and as CIPNM in another cluster. Patient demographic characteristics are reported in Table 1 .

Patients with non-COVID-19 ARDS were significantly younger than COVID-19 ARDS subjects ( Table 1 ). The most frequent comorbidities included type 2 diabetes, hypertension and obesity ( In Table 3 , we reported the mean values of neurophysiological data according to ARDS aetiology and presence of CIPNM. All patients with CIPNM regardless the aetiology showed significantly reduced CMAP amplitude in all explored muscles with the exception of the extensor digitorum brevis muscle without differences in the amount of reduction between the two groups of ARDS patients. No (Table 3) .

Concerning needle EMG, 32 over 44 (73%) patients were not cooperative and therefore could not perform voluntary recruitment. 

According to our analysis, a high incidence of CIPNM was observed in critically ill patients with ARDS from all the aetiologies with a TA B L E 2 Demographic, anamnestic and clinical findings in patients with (+) or without (-) critical illness polyneuropathy and myopathy

Peroneal MCV(m/s) 43 Finally, concerning the post-acute phase in the Intensive Rehabilitative Unit, patients with CIPMN could benefit from rehabilitation but may achieve lower functional outcomes. 47, 48 Thus, in addition to pulmonary rehabilitation, a physical motor rehabilitation should also be recommended to reduce symptoms of respiratory failure and distress and to restore the pre-illness functionality. 49,50

This study has some limitations. Firstly, since it was a retrospective study, the clinical and biochemical data were collected from patient charts and in some cases were incomplete (for example, there was a lack of information on markers of inflammation 

As the COVID-19 infection continues to spread, our understanding of the neurological manifestations in affected patients is also evolving. Considering the existing knowledge of other coronaviruses and respiratory viral infection pathogeneses, the extensive association of both central nervous system and peripheral nervous system manifestations with COVID-19 is not surprising. In particular, in the exploration of potential COVID-19-associated neurological diseases, the statistical probability of unique disease occurrence in the context of a pandemic is the data required to investigate causation appropriately. On the basis of a similar CIPNM incidence rate in our patient cohort between patients with COVID-19 infection compared to patients with ARDS from other aetiologies (65% of patients with COVID-19 infection and 71% of patients with ARDS from other aetiologies), we indirectly suggested the lack of increased correlation between COVID-19 infection and CIPNM onset. Therefore, we assume that the involvement of muscular tissue and peripheral nerves in COVID-19 patients might be secondary to critical illness; however, the problem relating to the interpretation of the possible different physiopathologies that lead to the development of the critical illness remains unclear about the possible viral mechanism. Therefore, further prospective multicentre trials, also based on quantitative ENG/ EMG, a more complete stratification of patients and the careful use of muscle biopsy are needed to provide a foundation for the data reported in our work. 

None of the authors has any conflict of interest to disclose. 

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

https://orcid.org/0000-0002-9997-8564

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