Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate order

doi:10.21203/rs.3.rs-3220709/v1

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Research Article

Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate order

https://doi.org/10.21203/rs.3.rs-3220709/v1

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Journal Publication

published 29 Dec, 2023

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Background

High flow nasal oxygen (HFNO) is recommended as a first line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF.

Methods

Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔP_es), clinical variables before and after 2 hours of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔP_es values and the relative change in breathing effort and clinical variables after 2 hours of HFNO was explored.

Results

Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔP_es (12 VS 16 cmH₂O, p < 0.0001), respiratory rate (RR) (22 VS 28 bpm, p < 0.0001), PaO₂/FiO₂ (133 VS 126 mmHg, p < 0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p < 0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 000.1). Patients with baseline ΔP_es below 20 cmH₂O where those who improved all the explored variables, while patients with baseline ΔP_es above 30 cmH₂O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔP_es values and after 2 hours of HFNO (R² = 0.9, p < 0.0001). ΔP_es change 2 hours after HFNO significantly correlated with change in BORG (p < 0.0001), ROX index (p < 0.0001), HACOR score (p < 0.001) and RR (p < 0.001).

Conclusions

In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

inspiratory effort

acute respiratory failure

high flow nasal oxygen

high flow nasal cannula

do not intubate order

patient’s self-inflicted lung injury

dyspnea

High-flow nasal oxygen (HFNO) therapy has been increasingly used in the management of patients with acute hypoxic respiratory failure (AHRF) in recent years^1,2. Indeed, various guidelines and expert consensus statements support its use as initial therapy in this setting, highlighting the potential benefits in improving oxygenation, reducing the need for endotracheal intubation, and potentially improving patient outcomes^3–5. Several studies provided evidence that HFNO therapy can mitigate the respiratory drive, as indicated by reduction in respiratory rate and work of breathing^6–11. Moreover, Bräunlich et al. specifically investigated the effect of HFNO on inspiratory effort as assessed by esophageal manometry in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)¹² showing a significant reduction in respiratory rate, inspiratory effort, and work of breathing. In this scenario, HFNO therapy can play a valuable role in managing the respiratory needs of patients who receive a "Do Not Intubate" (DNI) order, aligning with the goals of care outlined in the ceiling to treatment escalation¹³. Goals of care that preclude intubation and mechanical ventilation (MV) are more frequently decided by patients suffering from AHRF; thus, the individualization of the therapeutic approaches employed to support respiratory function is of pivotal importance to respect patient’s preferences and improve quality of life¹⁴. Furthermore, despite patients with DNI orders have a significantly increased risk of hospital mortality compared to patients without DNI orders, some studies suggest that more than half of all DNI patients with AHRF receiving some forms of respiratory support survive to hospital discharge¹⁵. Nevertheless, relieving inspiratory effort is the main goal in the management of these patients, in order to achieve effective palliation^14,15. Peters et al. examined the effect of HFNO on oxygen saturation and respiratory rate in 50 DNI patients with hypoxemic respiratory distress admitted to ICU and reported an improvement in average oxygen saturations and breathing frequency¹⁶. Further, in a study on 84 patients with AHRF associated to interstitial lung disease, HFNO was tolerated better than non-invasive ventilation (NIV) with no difference in 30-day survival nor in-hospital mortality¹⁷. Even though HFNO therapy may constitute an effective treatment option to comfortably assist the respiratory function in this specific population, there are clinical scenarios where HFNO may not provide sufficient support, resulting in respiratory distress persistence and favoring patient self-inflicted lung injury (P-SILI). Indeed, patients suffering from AHRF may exhibit an alteration of neural respiratory drive, related to inflammatory mechanisms and respiratory mechanics derangement, which may result in excessive inspiratory effort poorly responsive to pressure support or HFNO¹⁸. However, in DNI patients with AHRF, the effect of HFNO on inspiratory effort has not been elucidated yet. In this line, given that DNI patients cannot access to invasive controlled mechanical ventilation that turns off the respiratory drive, exploring the impact of HNFO on breathing effort during AHRF may be of clinical relevance. The primary aim of the study is to assess the effect of HFNO on inspiratory effort in a population of DNI patients suffering from AHRF. The correlation between the change in inspiratory effort after HNFO application and the variation in clinical respiratory indices and dyspnea served as secondary outcomes.

Study cohort

Patients with AHRF admitted to the Respiratory Intensive Care Unit (RICU) at the University Hospital of Modena between January 1st, 2018 and May 30th, 2023 were prospectively considered eligible for enrollment. This was a pre-planned sub-study of a prospectively registered protocol (ClinicalTrial.gov: ID NCT03826797). The local Ethics Committee (Comitato Etico Area Vasta Emilia Nord) approved the study (protocol number 4485/C.E., document 266/16) and informed consent was obtained from all participants or their relatives, as appropriate.

Inclusion criteria were: 1) age > 18 years; 2) presence of AHRF with with PaO₂/FiO₂ ratio < 200 mmHg during conventional oxygen therapy with Venturi mask with an inspiratory oxygen fraction (FiO2) of 0.6 and candidate to treatment escalation to HFNO; 3) DNI orders as expressed on a multidisciplinary and multicomponent ‘shared decision making’ basis considering patients and family goals of care, prognosis, baseline health (functional status, cognition, quality of life, living in a nursing home), age, frailty and comorbidities; esophageal manometry.

Exclusion criteria were: 1) the use of sedative regimens before RICU admission; 2) concomitant hypercapnia (PaCO₂ > 45 mmHg); 3) cardiogenic acute pulmonary edema; 4) previous diagnosis of interstitial lung disease, 5) neuromuscular disease, 6) diagnosis of active severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated disease (COVID-19). These latter categories were excluded due to the peculiar features of inspiratory effort reported during AHRF^19,20.

Clinical variables assessment and measurements

Demographics and clinical characteristics, comorbidities and clinical severity as assessed by the Sequential Organ Failure Assessment (SOFA) score were assessed at the time of RICU admission (T0). Arterial blood gases, hemodynamic parameters, the ratio between the partial pressure of oxygen and fraction of inspired oxygen (PaO₂/FiO₂ ratio), the Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, the Respiratory rate Oxygenation (ROX) index, values of esophageal pressure swing (ΔP_es) were collected at T0 and 2 hours after the application of HFNO (T1). HFNO failure within 24 hours and mortality was also recorded.

Physiological measurements

A multifunctional nasogastric tube with a pressure transducer (NutriVent^™, SIDAM, Mirandola, Italy) connected to a dedicated monitoring system (OptiVent^™, SIDAM, Mirandola, Italy) to record swings in esophageal pressures was placed before starting HFNO as previously reported²¹ and according to the recommended calibration protocol^22,23. All measurements were performed during a stable spontaneous breathing pattern of 3 minutes. Data sampling was numerically stored and downloaded via USB stick at each time of assessment. Offline breath-by-breath analysis was then performed for each measurement then averaged by a specific software (Flux View Respiratory Mechanics Monitor NBMED- Medical Graphics, Milano, Italy).

Management of high flow nasal oxygen

At our center, the criteria for being referred to RICU to upgrade to HFNO were in accordance with local protocols and included a peripheral oxygen saturation (SpO₂) < 90% during conventional oxygen therapy with Venturi mask and/or the presence of respiratory rate (RR) > 25 breaths/m(bpm) and/or the presence of subjective respiratory distress. HFNO was delivered with a high flow device (Optiflow^TMand AIRVO^™, Fisher & Paykel Healthcare Ltd, Auckland, New Zealand) through appropriately sized nasal cannulas. Flow delivery was initially set at 60 L/min and oxygen fraction at 50% and temperature at 37°C then adjusted according to the patient’s tolerance; oxygen fraction was then titrated to target a SpO₂ ≥ 92%. As per protocol, patients did not receive sedation with drugs affecting respiratory drive for the first 2 hours of HFNO treatment. Thereafter, the use of sedative regimens to reach a Richmond Agitation Sedation Scale within − 1 and 0 was allowed.

Outcome definition

The change in ΔP_es after 2 hours from HFNO application was identified as primary outcome. The change in clinical parameters and blood gas analysis after 2 hours from HFNO application and HFNO failure rate within 24 hours were also explored. HFNO failure was defined in the presence of the following: 1) PaO₂/FiO₂ ratio ≤ 100 mmHg and/or RR > 25 bpm and/or persistence of respiratory distress and dyspnea; in this case, patients may receive a trial of escalation to NIV if deemed indicated by the treating clinician; decision to escalate from HFNO to helmet/facemask NIV was taken by the attending physician, blinded to the results of esophageal manometry, according to clinical judgment; 2) switch to NIV; 3) death.

Analysis plan

In a previous work by our group, the application of HFNO was found to reduce ΔP_es after 2 hours from 13.5 cmH₂O to 8 cmH₂O (average reduction − 4.2, standard deviation [SD] 5.2 cmH₂O), in a population of patients with prevalently COVID-19 induced AHRF²⁰. Assuming α = 0.05, the accuracy of estimate = 0.5 cmH₂O and a margin of error of 5%, a sample size of 82 patients was sufficient to give value to the primary outcome.

Normality of data was assessed with visual inspection of quantile-quantile plots, and data are reported as median and interquartile range (IQR), if not stated otherwise. Categorical variables are expressed as frequencies and percentages. Continuous variables are compared using the Student t test or Mann-Whitney U test, as appropriate.

The change in physiological and clinical parameters according to the intensity of baseline breathing effort as assessed by esophageal manometry was also explored. During spontaneous breathing, the precise upper limit for a safe inspiratory effort is still to be identified. However, studies performed in critically ill patients under mechanical ventilation showed that ΔP_es ≥ 10 cmH₂O during a T-piece trial or immediately after extubation is usually associated with weaning failure^24,24. Thus, we consider ΔP_es < 10 cmH₂O as an acceptable/low inspiratory effort, while ΔP_es ≥ 10 cmH₂O as an index of abnormal effort. In order to stratify the level of effort as assessed by esophageal manometry, we arbitrarily categorized the baseline values of ΔP_es in 4 groups as follows: 1) ΔP_es < 10 cmH₂O (low effort); 2) 10 cmH₂O ≤ ΔP_es < 20 cmH₂O (intermediate effort); 3) 20 cmH₂O ≤ ΔP_es < 30 cmH₂O (high effort); 4) ≥ 30 cmH₂O (very high effort). Paired Student t test was used to compare values of ΔP_es and other clinical variables at different time points for each category. Other analyses were conducted to explore the correlation between the individual values of ΔP_es at baseline and after 2 hours of HNFO and the relative change in ΔP_es, BORG, ROX index, HACOR score and RR after 2 hours of HNFO. Correlation was sought using Pearson’s R or Spearman correlation coefficient as appropriate. A two-sided test of less than 0.05 was considered statistically significant. Statistics were performed using SPSS version 25.0 (IBM Corp.New York, NY, USA) and Graphpad prism version 8.0 (Graphpad Software, Inc. La Jolla, Ca, USA) unless otherwise indicated.

Patient characteristics

Eighty-two out of 114 consecutive patients admitted to the RICU in the considered time-lapse with AHRF and DNI orders who underwent esophageal manometry were enrolled (Fig. 1). Reasons for exclusion were presence of hypercapnia (N = 15), COVID-19 (N = 11), ongoing sedation (N = 8), cardiogenic pulmonary edema (N = 3), interstitial lung disease (N = 2) and neuromuscular disease (N = 1). The clinical characteristics of the study population at study inclusion is showed in Table 1. Patients were predominantly male (56.1%) with pneumonia being the most common reason for RICU admission (52.4%). COPD was present as a comorbidity in more than one-third of patients (36.6%) while more than half had hematologic or solid malignancy. Median SOFA score on admission was 4 IQR(3–8). More than one third of patients (n = 29) experienced HFNO failure within 24 hours and 21 (25.6%) died during their RICU stay.

Table 1

Characteristics of the study population
Variable	Value
Age, years (IQR)	71 (67–79)
Male, n (%)	46 (56.1)
BMI, kg/m² (IQR)	24 (22–26)
RICU admission diagnosis
Pneumonia, n (%)	43 (52.4)
ARDS, n (%)	39 (47.6)
Major comorbidities
Leukemia/lymphoma, n (%)	26 (31.7)
NYHA IV chronic heart failure, n (%)	24 (29.3)
Metastatic solid malignancy, n (%)	19 (23.2)
COPD, n (%)	30 (36.6)
Non-metastatic solid malignancy, n (%)	9 (11)
Dementia, n (%)	7 (3.7)
Charlson, index (IQR)	5 (4–7)
SOFA, score (IQR)	4 (3–8)
HFNO failure, n (%)	32 (39)
NIV upgrade, n (%)	29 (35.4)
Mortality, n (%)	21 (25.6)

BMI, body mass index, RICU, respiratory intermediate care unit, IQR, interquartile ranges, ARDS, acute respiratory distress syndrome NYHA, New York Heart Association, COPD, chronic obstructive pulmonary disease, SOFA, Sequential Organ Failure Assessment, HFNO, high flow nasal oxygen, NIV, non-invasive ventilation

Effect of HFNO on ΔP_esand clinical variables

The effect of HFNO on respiratory drive and other clinical variables is shown in Table 2. Two hours after HFNO start, patients presented lower ΔP_es values (T2 value showed first, 12 VS 16 cmH₂O, p < 0.0001) and RR (22 VS 28 bpm, p < 0.0001) as compared to baseline. Blood gas exchanges (PaO₂/FiO₂ 133 VS 126 mmHg, p < 0.0001, pCO₂ 34.3 VS 33 mmHg), clinical scores (HACOR 4 VS 6, p < 0.0001, ROX index 8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 0.001) also resulted significantly improved.

Table 2

Characteristics of the study population and measurements (baseline and 2-hour apart from HFNO initiation)
Variable	Baseline (T0)	2 hours apart from HFNO start (T1)	p
HACOR, score (IQR)	6 (3–7)	4 (2–5)	< 0.0001
ROX, index (IQR)	5.7 (4.3–8.3)	8.5 (5.4–11.9)	< 0.0001
BORG (score)	4 (2–7)	1 (0–6)	< 0.0001
PaO₂/FiO₂, mmHg (IQR)	126 (94–170)	133 (104–191)	< 0.0001
FiO₂, % (IQR)	55 (45–70)	48 (35–58)	< 0.0001
PaO₂, mmHg (IQR)	66.9 (60–76.1)	63.2 (60–68)	< 0.0001
PaCO_2, mmHg (IQR)	33 (31–35)	34.3 (32–36.3)	< 0.0001
HR, bpm (IQR)	98 (87–112)	93 (87–103)	< 0.0001
RR, bpm (IQR)	28 (25–36)	22 (20–28)	< 0.0001
Lactate, mmol/L (IQR)	1.6 (1.1–2.7)	1.5 (1–2.2)	0.0002
BE, mmol/L (IQR)	-1 (-2–0)	-0.5 (-3–1)-	0.05
HCO3-, mEq/L (IQR)	23 (22–24)	23.5 (21–25)	0.08
ΔP_es, cmH₂O (IQR)	16 (9–29)	12 (6–27)	< 0.0001

HFNO, high flow nasal oxygen, ROX, respiratory rate oxygenation, BMI, body mass index, IQR, interquartile ranges, HR, heart rate, RR, respiratory rate, BE, base excess, ΔP_es, esophageal pressure swing.

Sensitivity analyses

The change in ΔP_es, PaO₂/FiO₂, RR and BORG scale after 2 hours of HNFO according to the intensity of baseline breathing effort is showed in Fig. 2. The reduction of ΔP_es resulted significant for patients who presented a baseline value below 20 cmH₂O (panel A, Fig. 2). HFNO treatment resulted in a significant decrease of perceived dyspnea and RR for patients with baseline ΔP_es value below 30 cmH₂O (panel C and D, Fig. 2) while PaO₂/FiO₂ significantly improved only for patients with baseline breathing effort below 20 cmH₂O.

Figure 3 has been obtained by plotting the individual value of ΔP_es after 2 hours of HNFO and its relative change from baseline and showing HFNO failure by means of closed symbols. All the patients who failed HFNO were unable to reduce their breathing effort within 2 hours and/or presented ΔP_es value ≥ 20 cmH₂O after HFNO application. None of the patients that presented a ΔP_es below 10 cmH₂O following 2 hours of treatment experienced HFNO failure. All the patients that presented a baseline value of ΔP_es > 30 cmH₂O, still showed elevated values of ΔP_es (> 20 cmH₂O) two hours after HFNO start and further experienced HFNO failure. A significant correlation between ΔP_es values measured at baseline and after 2 hours of HFNO was found (R² = 0.9, p < 0.0001, eFigure 1, Supplementary materials). All the patients who failed HFNO showed ΔP_es values above 20 cmH₂O after 2 hours of treatment. The change in breathing effort 2 hours after HFNO resulted significantly and moderately correlated with change in perceived dyspnea as assessed by BORG (r = 0.63 95%CI[0.47–0.75], p < 0.0001, panel A, eFigure 2, Supplementary materials). A weak to moderate significant correlation was also found between ΔP_es change and the variation of ROX index (r= -0.57 95%CI[-0.7 - -0.4], p < 0.0001, panel B, eFigure 2, Supplementary materials), HACOR score (r = 0.37 95%CI[0.17–0.55], p < 0.001, panel C, eFigure 2, Supplementary materials) and RR (r = 0.49 95%CI[0.31–0.64], p < 0.001, panel D, eFigure 2, Supplementary materials) following HFNO application.

Our study shows that in a population of patients with AHRF and DNI orders the use of HFNO significantly improved inspiratory effort, respiratory rate, gas exchange and perceived dyspnea 2 hours after its application. However, for a proportion of patients exhibiting an excessive baseline activation of respiratory drive (ΔP_es > 30 cmH₂O, n = 18), HFNO was not effective in reducing respiratory distress and failed within 24 hours. Further, the change in ΔP_es within 2 hours from HFNO start was significantly moderately correlated with BORG, while the correlation with other clinical indices of respiratory distress (ROX, HACOR, RR) resulted in weak to moderate.

HFNO and inspiratory effort in DNI patients

Although most studies in AHRF have focused exclusively on patients without preset limits on life support, a recent meta-analysis by Wilson et al. showed that up to 25% of patients undergoing NIV or HFNO for AHRF have a DNI order, with increasing rates over time²⁵. Placement of DNI orders and thus withholding of MV may favor treatment strategies that honor patient preferences and pursue patient-centered goals²⁶. In this scenario, providing timely palliative interventions with adequate symptoms relief represents a major issue¹³. However, it has been reported that more than half of all patients with a DNI order who receive non-invasive respiratory support for AHRF survive to hospital discharge—often with no worse quality of life compared to those with no ceiling to treatment escalation¹⁵. Moreover, the use of NIV in patients with preset limits on life support has been called into question, given that its burdens (namely patient’s discomfort) may outweigh potential benefits²⁷. Thus, the optimal management of DNI patients with AHRF is far more challenging than mere symptoms control and would benefit from tailoring the respiratory assistance based on clinical and physiological variables. Our study shows that HFNO can early relieve breathing effort but only for patients with ΔP_es below 20 cmH₂O. This finding is in line with what reported by Mauri et al. in 15 patients with AHRF with average ΔP_es = 9.9 ± 4.2 cmH₂O, where HFNO significantly improved breathing effort compared with conventional oxygen supply⁷. However, a study by our group showed that patients with moderate to severe AHRF may reach an average baseline value of ΔP_es up to 34 cmH₂O²¹. Therefore, considering on data from this study, it is reasonable to assume that a significant proportion of patients with AHRF may not respond to HFNO in terms of work of breathing reduction. Whether the use of a different respiratory support (namely, NIV) may be more adequate to mitigate respiratory discomfort in this subgroup of patients is still debated. Indeed, the hyperactivation of respiratory drive in AHRF depends on a complex interaction of factors, including gas exchange, lung mechanical derangement, inflammatory stimuli and cortical triggers²⁸. The identification of AHRF patients for whom the application of non-invasive respiratory support has no effect on inspiratory effort may lead the attending clinician to consider a pharmacological strategy to modulate the respiratory drive in order to mitigate patient’s discomfort. Conversely, those patients who benefit the most from respiratory assistance may have conservative sedative interventions aimed at sparing side effects and pharmacological interactions.

HFNO and dyspnea in DNI patients

Dyspnea is a debilitating symptom that affects quality of life in various respiratory conditions and is associated with poor outcomes²⁹. However, the mechanisms of dyspnea remain not completely understood, being a subjective experience whose objective measurements still challenge clinicians. Further, like reports of pain, the description of dyspnea may be influenced by cultural and linguistic factors, as well as patient’s ability to communicate during distress. However, in most DNI patients, dyspnea relief represents the focus on which the different non-invasive respiratory supports (HFNO, NIV) are targeted³⁰,³¹. Thus, an objective variable to use and monitor at bedside that reflects the real respiratory discomfort experienced by the patient may improve the palliative goal of treatment. Our study showed the change in ΔP_es 2 hours after HFNO is correlated with the variation of dyspnea. This may indicate the benefit achieved by HFNO in relieving shortness of breath could lay in the reduction of breathing effort. Further, in patients with DNI orders on HFNO, we suggest timely assessment of dyspnea since it has been shown to be correlated with respiratory effort, and, thus, with the risk of HFNO failure.

Strengths and limitations

To our knowledge this is the first study that assesses the effect of HFNO on inspiratory effort in DNI patients with AHRF. Further, the sample is wide enough to confidently preform analysis on the primary outcome. Nevertheless, our study still has several limitations. First, data on dyspnea as assessed by BORG was available only for a proportion of patients (n = 74). Second, the use of esophageal manometry may appear disproportionate in DNI patients and results might not be applicable in clinical practice. In this line, the precise bedside assessment of dyspnea could be a valid surrogate to estimate inspiratory effort; this may allow to forecast HFNO outcomes and to identify patients who may benefit from respiratory drive control measures, such as sedation. Our results showed a significant, although weak, correlation between ΔP_es change within 2 hours from HFNO start and variation of clinical indices of respiratory distress. Thus, the integration of these variables with non-invasive tools to assess inspiratory effort (namely ΔP_nose) may improve the management of DNI patient with AHRF. Also, the single-center design may limit the external validity of our results. Furthermore, the study was conducted in a center with high expertise in assessing breathing effort; thus, the switch to NIV may have been influenced by close monitoring of signs of increased work of breathing, even though the attending physicians were blinded to esophageal manometry. Our study population consisted of a heterogeneous cohort of patients with DNI orders with different trajectories of their disease and various comorbidities. The interaction between the baseline disease and AHRF may have acted as effect modifier for the impact of HFNO on the change in respiratory effort. Finally, the sedative regimens allowed after 2 hours of HFNO were not standardized, and some patients may have received sedatives (i.e. opioids) for pain management due to baseline comorbidities; therefore, a potential interaction between the use of pharmacological management and HFNO failure/success at 24 h cannot be excluded.

The use of HFNO to assist DNI patients with AHRF resulted effective in mitigating breathing effort and improving respiratory and clinical variables, such as dyspnea only for those patients with not excessive inspiratory effort. Further research is warranted on how to tailor the respiratory assistance to the goals of care outlined for DNI patients.

AHRF, acute hypoxic respiratory failure, ARDS, acute respiratory distress syndrome, DNI, do not intubate, bpm, breaths per minute, MV, invasive mechanical ventilation, HFNO, high flow nasal oxygen, SOFA, sequential organ failure assessment, RICU, respiratory intermediate care unit, ΔP_es, esophageal pressure swing, IQR, interquartile range, COPD, chronic obstructive pulmonary disease, P-SILI patient self-inflicted lung injury, PaO₂/FiO₂ ratio between the partial pressure of oxygen and the fraction of inspired oxygen, HACOR, Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate, ROX, respiratory rate oxygenation

Ethics approval and consent to participate

This study was conducted in accordance with Ethics Committee “Area Vasta Emilia Nord” approval (registered protocol number 216/16). Informed consent to participate in the study and to allow their clinical data to be analyzed and published were obtained from participants, as appropriate.

Consent for publication

Informed consent was waived because of the retrospective nature of the study and the analysis used anonymous clinical data.

Availability of data and materials

Data are available at the Respiratory Disease Unit of the University Hospital of Modena, Italy, upon request.

Competing interests

Authors have no competing interests with any organization or entity with a financial interest in competition with the subject, matter or materials discussed in the manuscript.

Funding

No funding available.

Author contributions

RT and RF designed the study, enrolled the patients, analyzed the data, and wrote the paper and should be considered as first authors. AC, LP, CC, LT, IC and A Moretti made substantial contributions to the literature review, data collection, and paper writing. G Bruzzi, DP, FG, SR, MT, BR, and G Bellesia reviewed the literature, wrote the manuscript, and produced the figures. EC and A Marchioni designed the study, wrote, reviewed, and edited the manuscript. All authors have read and approved the final version of the manuscript. RT and RF share first authorship. EC and AM share senior authorship.

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published 29 Dec, 2023

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Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate order

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Abstract

Figures

INTRODUCTION

MATERIALS AND METHODS

Study cohort

Clinical variables assessment and measurements

Physiological measurements

Management of high flow nasal oxygen

Outcome definition

Analysis plan

RESULTS

Patient characteristics

Sensitivity analyses

DISCUSSION

HFNO and inspiratory effort in DNI patients

HFNO and dyspnea in DNI patients

Strengths and limitations

CONCLUSION

Abbreviations

Declarations

References

Supplementary Files

Status:

Journal Publication

Version 1