We are amidst a coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2. Oxygen administration is crucial in COVID-19 treatment and, unlike conventional oxygen therapy, high-flow nasal cannulas (HFNCs) prevent the need for intubation in patients with acute respiratory failure [1,2]. However, HFNC use is limited owing to concerns of aerosol generation. Accumulation of data on experiences with HFNC in COVID-19 might help to convince institutions to use HFNC; thus, we report our single-center experience with HFNCs for patients with COVID-19.
Patients using HFNC were retrospectively identified from among 266 patients admitted to our hospital due to COVID-19 between January and September 2020. HFNC is implemented when oxygenation cannot be maintained by an oxygen mask (with reservoir bag). Our institution currently lacks a clear protocol for HFNC initiation; instead, its use depends on clinical physician judgment. We adopted the F & P 850 system (Fisher & Paykel Healthcare) for HFNC therapy with a temperature setting of 37.0 °C and absolute humidity of 44 mg/L. The flow rate and fraction of inspired oxygen (FiO2) were adjusted according to individual clinical physician preferences. We classified patients administered HFNC therapy due to condition deterioration as HFNC success or failure, depending on whether intubation could be avoided. Patients who died without intubation due to do-not-attempt-resuscitation (DNAR) orders were classified as HFNC failure.
Fifteen patients (88.2%) required HFNC due to deterioration with a median time-to-HFNC of 10 days after symptom onset. The median age was 68 years and 12 patients (80%) were men. The median oxygen demand before HFNC was 8.0 L/minute. Baseline treatment was determined by each department and included remdesivir, (9 patients, 60%), hydroxychloroquine (3 patients, 23%), favipiravir (2 patients, 13.3%), lopinavir-ritonavir (1 patient, 6.7%), and corticosteroid (14 patients, 93.3%) (Table 1 ). Regarding baseline vital signs, the median saturation of percutaneous oxygen (SpO2)/FiO2 was lower in the HFNC failure group than that in the HFNC success group (Table 2 ). HFNC success, rather than HFNC failure, tended to increase the respiratory rate (RR). This might have occurred by “silent or happy hypoxia” because the HFNC failure patients received HFNC at a comparatively early phase, with a median days-to-HFNC after onset of 9 days vs. 12.5 days for the HFNC success group [3] (Table 1). Otherwise, two patients required HFNC after extubation and both recovered without re-intubation.
Table 1.
Baseline characteristics of patients administered HFNC therapy due to condition deterioration. HFNC, high-flow nasal cannula.
| Total (n = 15) | HFNC success (n = 8) | HFNC failure (n = 7) | |
|---|---|---|---|
| Age (years), median (IQR) | 68 (64–77) | 67.5 (59–76.5) | 74 (68–76) |
| Gender (Male), n (%) | 12 (80%) | 7 (87.5%) | 5 (71.4%) |
| Body mass index (kg/m2), median (IQR) | 26.4 (22.4–28.2) | 26.0 (23.8–27.5) | 27.7 (21.9–29.0) |
| Comorbidity | |||
| Hypertension | 11 (73.3%) | 5 (62.5%) | 6 (85.7%) |
| Diabetes mellitus | 9 (60%) | 4 (50%) | 5 (71.4%) |
| Dyslipidemia | 6 (40%) | 2 (25%) | 4 (57.1%) |
| COPD | 3 (20%) | 1 (12.5%) | 2 (28.6%) |
| Asthma | 1 (6.7%) | 1 (12.5%) | 0 |
| Coronary heart disease | 3 (20%) | 2 (25%) | 1 (14.3%) |
| Chronic kidney disease | 6 (40%) | 1 (12.5%) | 5 (71.4%) |
| Immunosuppression | 0 | 0 | 0 |
| Smoking status | |||
| Non-smoker | 6 (40%) | 5 (62.5%) | 1 (14.3%) |
| Current smoker | 4 (26.7%) | 2 (25%) | 2 (28.6%) |
| Former smoker | 5 (33.3%) | 1 (12.5%) | 4 (57.1%) |
| Implementation of HFNC | |||
| Days after onset (days), median (IQR) | 10 (5–13) | 12.5 (7–13.3) | 9 (5–10.5) |
| Days after admission (days), median (IQR) | 1 (1–2.5) | 1 (1–2.3) | 2 (1–2.5) |
| Oxygen demand before HFNC (L), median (IQR) | 8 (7.5–10) | 8 (6.8–8) | 10 (9–10) |
| Baseline treatment | |||
| Remdesivir, n (%) | 9 (60%) | 5 (62.5%) | 4 (57.1%) |
| Hydroxychloroquine, n (%) | 3 (23%) | 1 (12.5%) | 2 (28.6%) |
| Favipiravir, n (%) | 2 (13.3%) | 2 (25%) | 0 |
| Lopinavir-ritonavir, n (%) | 1 (6.7%) | 0 | 1 (14.2%) |
| Steroid, n (%) | 14 (93.3%) | 8 (100%) | 6 (85.7%) |
| Clinical trial, n (%) | 4 (26.7%) | 3 (37.5%) | 1 (14.2%) |
HFNC, high-flow nasal cannula; IQR, interquartile range; COPD, chronic obstructive pulmonary disease.
Table 2.
Outcomes after HFNC therapy, HFNC, high-flow nasal cannula.
| Total (n = 15) | HFNC success (n = 8) | HFNC failure (n = 7) | |
|---|---|---|---|
| Baseline | |||
| HR (bpm), median (IQR) | 94 (72–97) | 84 (73.3–94.5) | 97 (82–107) |
| RR (/min), median (IQR) | 24 (21.5–30.5) | 28.5 (22.5–32.8) | 22 (21.5–24) |
| SpO2/FiO2, median (IQR) | 131.4 (118.1–153.9) | 135.7 (130–172.4) | 116.3 (115.6–128.6) |
| 2 – 6 h after HFNC | |||
| HR (bpm), median (IQR) | 74 (68.5–90) | 73 (69.3–79) | 76 (65.5–91.5) |
| RR (/min), median (IQR) | 24 (21–24.5) | 23 (21.5–24) | 25 (22–26) |
| SpO2/FiO2, median (IQR) | 188 (140.8–225.1) | 203.9 (174.1–247.9) | 180 (130.3–191) |
HFNC, high-flow nasal cannula; IQR, interquartile range; HR, heart rate; RR, respiratory rate; SpO2, saturation of percutaneous oxygen; FiO2, fraction of inspired oxygen.
Of the 15 patients administered HFNC, 8 (53.3%) avoided intubation. Six patients (40%) required intubation and one patient (6.7%) died without intubation due to a DNAR order. The median HFNC duration in the HFNC success and intubated HFNC failure patients were 5 days and 2.5 days, respectively. The median maximum FiO2 values were 62.5% and 95%, respectively. Of the six patients intubated, four were extubated and discharged and two patients died. A total of three patients (20%) died, none of whom were in the HFNC success group (Table 3 ). Regarding sequential changes in vital signs, SpO2/FiO2 and heart rate (HR) improved in both groups after 2–6 hours of HFNC use. However, RR was aggravated in the HFNC failure group (Table 2).
Table 3.
Sequential changes after HFNC therapy. HFNC, high-flow nasal cannula.
| Total (n = 15) | HFNC success (n = 8) | HFNC failure (n = 7) |
||
|---|---|---|---|---|
| Intubation (n = 6) | Without intubation (n = 1) | |||
| HFNC duration (days), median (IQR) | 5 (2.5–6) | 5 (3.75–6.25) | 2.5 (2–4.5) | 7 |
| HFNC setting | ||||
| Maximum flow rates (L/min), median (IQR) | 50 (50–50) | 50 (50–50) | 50 (50–57.5) | 60 |
| Maximum FiO2 (%), median (IQR) | 80 (62.5–97.5) | 62.5 (60–68.75) | 95 (86.3–100) | 100 |
| Oxygen demand after HFNC (L/min), median (IQR) | N/A | 4 (4–4.25) | N/A | N/A |
| Death, n (%) | 3 (20%) | 0 | 2 (33.3%) | 1 (100%) |
HFNC, high-flow nasal cannula; IQR, interquartile range; FiO2, fraction of inspired oxygen, N/A, not available.
All patients administered HFNC used a private negative pressure room. We requested that the patients use a surgical mask if possible; however, not all patients were able to comply due to discomfort caused by high temperature and humidity.
Staff providing COVID-19 medical treatment underwent personal protective equipment (PPE) donning and doffing training beforehand. Medical care staff donned PPE including long-sleeved gowns, gloves, N95 masks, surgical masks with face shields, and hair caps while attending to patients with HFNC as well as conventional oxygen therapy. These staff usually entered the HFNC treatment area more frequently than the conventional oxygen therapy area; however, there was no restriction on the entrance frequency into the HFNC treatment area.
Nosocomial infections were not apparently reported during the study period. In July 2020, we conducted antibody tests on 1228 hospital staff, during which time 11 patients were using HFNCs. A total of 850 people were engaged in work associated with COVID-19; of these, 343 (40%) worked in high-risk conditions. Only two (0.16%) staff tested positive; however, they were not involved in COVID-19-related work. Thus, none of the healthcare workers providing COVID-19 medical care was antibody-positive [4].
Concerning the physio-pathological considerations that may benefit from HFNC, Gattinoni et al. reported that hypoxemia in early-phase COVID-19 results from ventilation/perfusion mismatch [5]. Thus, these patients may benefit from HFNC during the initial stage of the disease. HFNC may also play a crucial role in flushing the anatomical dead space, providing a positive expiratory pressure effect, reducing work of breathing, providing humidification, and increasing tolerance [6]. Furthermore, reducing the respiratory drive can help prevent patient self-inflicted lung injury as a potential contributory cause of lung damage and consequent worsening of respiratory failure [5].
Some guidelines have recommended HFNC despite the weak evidence [7], while some clinical practice guidelines have conditionally approved HFNC against concerns of nosocomial infection [[8], [9], [10]]. Additionally, in simulations, properly fitted HFNC limits the airborne dispersion of bioaerosols [11] to levels equivalent to those of a standard oxygen mask [12]. However, there is a risk of bioaerosol dispersion with loosely fitted HFNC [11]. As mentioned above, the use of HFNC for COVID-19 is controversial; thus, its use should be discussed in each facility.
Nosocomial COVID-19 infections caused by HFNC did not apparently occur at our hospital because the environment and facilities were adequately managed. Systematic reviews on HFNC effectiveness and safety have shown that optimal management might vary depending on the equipment and the availability of ventilators [13]. If possible, the use of a surgical mask in patients receiving HFNC is reasonable and beneficial because it reduces infectious droplet spread [12,14].
This study has two limitations. First, as there was no clear protocol for HFNC initiation, the treatment results may vary depending on the judgment of individual clinical physicians. Secondly, this was a single-center study with a limited number of cases.
In conclusion, the appropriate use of HFNC is beneficial because it can reduce intubation rates without nosocomial infection. Furthermore, it can relieve the current strain on medical systems. Since it might take time for the COVID-19 pandemic to resolve, HFNC use should be considered depending on the facility environment and availability of respiratory equipment.
Conflict of Interest
The authors have no conflicts of interest.
Acknowledgments
The authors thank all National Center for Global Health and Medicine staff who provided medical care to COVID-19 patients and Editage (https://www.editage.jp/) for English language editing.
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