Noninvasive Ventilation

Patients were classified as having limb, bulbar or diaphragmatic onset ALS. For the purposes of analysis, those with diaphragmatic onset were classified with those with limb onset because of the common spinal basis of lower motor neuron degeneration. ALS milestones for investigation as potential staging criteria were selected on the basis of being easily clinically available by being routinely collected at any clinical visit, straightforward to define in terms of presence or absence of involvement, and useful for phenotypic classification (Wijesekera et al., 2009 (link)). Milestones were defined as symptom onset (functional involvement by weakness, wasting, spasticity, dysarthria or dysphagia of one CNS region defined as bulbar, upper limb, lower limb or diaphragmatic), diagnosis, functional involvement of a second region, functional involvement of a third region, needing gastrostomy and non-invasive ventilation. As wasting was almost always associated with weakness, and for patients with ALS spasticity manifests as weakness, we did not differentiate between those patients whose onset was not weakness, but rather spasticity or wasting without weakness. Timing of involvement was based on the date of onset of symptoms and dates of development of functionally significant symptoms in a second and third region, which were gathered from the clinical history. Diagnosis was defined as a confirmed diagnosis of ALS made either by the referring neurologist or at the tertiary centre, as recorded in the case records. The need for gastrostomy was defined as the time gastrostomy or nasogastric feeding was provided or refused. The need for non-invasive ventilation was defined as the time non-invasive ventilation was provided, trialled or refused.
Milestone timings were standardized as proportions of time elapsed through the disease course using information from patients who had died by dividing time to a milestone by disease duration, a similar method to that used in a previous study of timings of medical interventions (Bromberg et al., 2010 (link)). Thus the time to each milestone was a value between 0 and 1, with 0 being symptom onset and 1 being death. Date of death was ascertained by clinic records, death certificates and contact with the patient's registered general practitioner. The highest milestone recorded at last follow-up was used. Riluzole use was also recorded and defined as any use longer than 2 weeks.

This retrospective and cross-sectional study was conducted in Trakya University Hospital Respiratory Intensive Care Units which was approved by the Trakya University Clinical Research Ethics Committee (TÜTF-BAEK 2021/275) and the Turkish Ministry of Health (2021-06-07T10_06_44). Patients diagnosed with ARF due to lung involvement of laboratory-confirmed (RT-PCR) COVID-19 and managed with HFNC at ICU admission were included in the study between April 2020 and January 2022.
As per the Turkish Ministry of Health COVID-19 management guideline,²¹ HFNC is indicated for patients with persistent hypoxemia or respiratory distress symptoms under low flow oxygen therapy systems. HFNC was administered in the ICU with HI-Flow Star^TM (Dragerwerk AG & Co., Germany), which is set to deliver a flow rate up to 50 l/min with FiO₂ to keep the patient’s SpO₂ above 90%.
If deterioration in the patient’s level of consciousness, worsening dyspnea, malign arrhythmia, or hemodynamic instability were detected or more than 60% FiO₂ under 50 l/min flow rate was required to keep the patient’s PaO₂/FiO₂ over 150 mmHg, it was considered a treatment failure. Non-invasive ventilation (NIV) or IMV was initiated as rescue therapy.
Data were abstracted from the hospital records and nurse charts. Patients’ demographics, body mass indices, comorbidities, Charlson Comorbidity Indices,^{22 (link)} disease severity scores [Acute Physiology and Chronic Health Assessment (APACHE),^{23 (link)} Sequential Organ Failure Assessment (SOFA)^{24 (link)}] and laboratory findings (hemogram, d-dimer, ferritin, C-reactive protein, procalcitonin, arterial blood gas parameters within 2 hours thereafter HFNC initiation) at ICU admission; ROX indices at initiation, 2^nd, 8^th, 12^th, 24^th and 48^th hours of HFNC; and out-comes (ICU and hospital length of stay, in 28-day mortality) were recorded (Figure 2). ROX index was calculated using the formula (SpO₂/FiO₂)/respiratory rate.^{18 (link)} Patients were excluded who were younger than 18 years old and HFNC failed within 2 hours of the therapy.