Effectiveness of high flow nasal cannula oxygen therapy in patients of acute pulmonary thromboembolism with acute hypoxemic respiratory failure

Abstract

Background

Acute Pulmonary thromboembolism (PTE) is associated with acute hypoxemic respiratory failure (AHRF), which is a leading cause of death in these patients. High-Flow Nasal Cannula (HFNC) oxygen therapy is a cornerstone of the treatment of respiratory failure. The aim of the present study is to explore the efficacy of HFNC in the treatment of patients of acute PTE with acute hypoxemic respiratory failure in India.

Methods

This is a retrospective study of patients admitted to a tertiary care center with acute PTE with AHRF during the period from January 2018 to January 2020. After reviewing medical files, patients of acute PTE with AHRF treated with HFNC were included in the study. We analyzed the improvement in oxygenation parameters and respiratory rate, as well as outcome in these patients.

Results

During the above specified period, 12 patients suffering from PTE with AHRF were treated with HFNC. After 1 h of the initiation of HFNC along with anticoagulation, the respiratory parameters of patients significantly improved. HFNC was applied for a period of 6–10 days. None of the patients required intubation for AHRF, and all patients were discharged from the hospital on oral anticoagulants.

Conclusion

HFNC oxygen therapy in patients with acute PTE with AHRF showed rapid improvement of oxygenation and respiratory rate. HFNC oxygen therapy is an efficacious treatment for patients with AHRF secondary to acute PTE without any significant hemodynamic effect. It acts as a superior modality of oxygen therapy avoiding noninvasive and invasive ventilatory support.

Introduction

Acute Pulmonary thrombo embolism (PTE) is a dreaded complication secondary to various etiologies. PTE is a part of the concoction of a large multifarious clinicopathological entity, venous thromboembolism, which is associated with high mortality and morbidity.¹ High-Flow Nasal Cannula (HFNC) oxygen therapy has become a prime modality of the management of patients with Type 1 respiratory failure. Its superiority upon noninvasive ventilation (NIV) and conventional oxygen therapy (COT) is established for mortality reduction and avoidance of intubation in patients with acute hypoxemic respiratory failure (AHRF). HFNC therapy delivers a high flow rate of oxygen and has added benefit of providing essentially required minimum positive end-expiratory pressure (PEEP) to AHRF patients. Acute respiratory failure and ventricular failure with resulting reduced systemic output to vital organs are the leading causes of death in patients with acute PTE. Supportive oxygen therapy is essential in patients with acute PTE who develop hypoxemia and respiratory failure.² Type 1 Respiratory failure (AHRF) is defined as PaO₂ less than 60 mm Hg with normal or low PaCO₂.³ All the cases of our study have Type 1 Respiratory failure. Prompt diagnosis of acute PTE is decisive because of the associated high mortality and morbidity, which may be prevented with early treatment and intervention.⁴ Endogenous fibrinolysis plays a vital role in impeding the continuous propagation of a growing thrombus in PTE.⁵ Patients with acute PTE and hypoxemic respiratory failure who do not tolerate NIV frequently get intubated due to high oxygen requirement and endotracheal intubation leads to a poor patient outcome and prognosis. HFNC oxygen therapy is the latest method of providing a high flow of heated and humidified oxygen to the patient. It is superiorly tolerated compared to NIV, as it provides high fraction of inspired oxygen (FiO₂) and minimal essential PEEP via nasal prongs.⁶ HFNC gives a prompt improvement in respiratory parameters without any significant hemodynamic side effect and work as a scion to allow a time frame for endogenous fibrinolysis.⁷ The role of HFNC oxygen therapy in patients of hypoxemic respiratory failure in the subgroup of patients with acute PTE has not been studied in India as per the author's knowledge. The aim of this present study is to explore the efficacy of HFNC oxygen therapy in the treatment of patients with acute PTE with AHRF.

Material and methods

This is a retrospective study of 12 patients admitted to a tertiary care center with acute PTE with AHRF during the period from January 2018 to January 2020. After reviewing medical files, patients treated with HFNC oxygen therapy for acute PTE with AHRF who required more than 6 L/min oxygen on nasal prong to achieve more than 92% of oxygen saturation (SpO₂) along with PaO₂/FiO₂ < 300 were included in the study. The study was approved by the ethics committee of the hospital and informed consent was obtained from all the subjects. Patient selection criteria included those diagnosed radiologically as cases of acute PTE and who developed AHRF. Patients intubated (requiring mechanical ventilation) after the diagnosis of PTE and patients with oxygen requirement less than 6 L/min (FiO₂ approximately less than 40%) were excluded from the study. The baseline data of the selected patients were collected, which included age, gender, duration of symptoms, oxygenation parameters, chest radiograph, Computed Tomography Pulmonary Angiography (CTPA) of the chest, and arterial blood gas (ABG). Anticoagulation using low molecular weight heparin and HFNC Oxygen Therapy at the maximum rate of 60 L/min was administered to these patients with a maximum FiO₂ of 1.

Results

Characteristics of PTE – HFNC treated patients

During the above specified period, 12 patients suffering from PTE with AHRF were admitted to our center. Breathlessness was the commonest presenting symptom in all patients, and four patients had chest pain. The ages of the participants were with a minimum to maximum range of 37 to 72 yrs (Median and mean age 52 yrs with standard deviation (SD) 11.25). There were 92% men as compared to 8% women in the study. The SpO₂ parameters at presentation were with a minimum to maximum range of 70% to 87% (Median SpO₂ 83% and Mean SpO₂ 81% with SD 5.3). PaO₂ in mm Hg at presentation were with a minimum to maximum range of 37 to 57 (Median PaO₂ 51 and Mean PaO₂ 49 with SD 7) on room air. The respiratory rate per minute of the participants were with a minimum to maximum range of 28 to 38 (Median and mean respiratory rate 32 with SD 3). The patient’s characteristics are summarized in Table 1. Most of the patients had normal chest radiographs while the CTPA scan reports diagnosed PTE (Fig. 1, Fig. 2, Fig. 3, Fig. 4). ECG showed sinus tachycardia in all patients. 2D Echo showed the presence of paradoxical septal motion in most of the cases.

Table 1.

Base Line Characteristics Of PTE With AHRF Patients At The Time of Presentation.

Features	Case 1	Case 2	Case 3	Case 4	Case 5′	Case 6	Case 7	Case 8	Case 9	Case 10	Case 11	Case 12
Age (yrs)	48	39	43	72	59	56	56	37	48	39	65	66
Gender	M	M	M	M	M	M	M	M	F	M	M	M
Duration of dyspnoea	02 days	04 days	10 days	30 days	03 days	05 days	04 days	01 day	15 days	07 days	01 day	02 days
Duration of chest pain	02 days	02 days	Nil	Nil	Nil	03 days	Nil	Nil	05 days	Nil	Nil	Nil
Resp Rate(Rate/Minute)	32	34	30	36	36	38	30	28	32	30	32	30
BP at presentation (mm of Hg)	102/64	100/66	106/68	104/62	100/60	104/62	100/64	102/62	104/62	106/66	104/60	108/68
Heart rate at presentation (beats/Minute)	118	125	120	132	136	128	130	116	120	114	116	117
SpO2 (%) at room air	84	80	82	75	70	74	82	87	86	86	84	86
ABG Analysis-pH	7.46	7.47	7.44	7.43	7.41	7.44	7.42	7.40	7.39	7.47	7.38	7.46
PaO2 (mm Hg) at room air.	52	46	49	39	37	38	50	57	56	55	53	55
PCO2 (mm Hg)	38	36	39	37	40	35	40	39	40	42	38	37
HCO3-(meq/L)	23.1	22.9	23.8	26.2	24.9	23.2	24.8	25.3	26.5	23.4	28.1	24.9
BE (mmol/L)	−1.2	+1.1	−1.5	+1.2	+1.0	−1.5	−1.	+1.3	−1.2	−1.4	+2.0	+1.8
P/F Ratio at room air (FiO2-21%)	247	219	233	185	176	180	238	271	266	261	252	261
ECG	Sinus Tachycardia,	Sinus Tachycardia	Sinus Tachycardia. S1, Q3, T3	Sinus Tachycardia,S1,Q3,T3	Sinus Tachycardia	Sinus Tachycardia,	Sinus Tachycardia	Sinus Tachycardia	Sinus Tachy cardia,	Sinus Tachycardia	Sinus Tachy cardia.	Sinus tachycardia,
Chest X-ray	NAD	NAD	NAD	Blunted bilateral costophrenic angle.	Prominent broncho vascular markings	Prominent broncho vascular markings	NAD	Blunted left costo phrenic angles	NAD	NAD	NAD	NAD
Location of clot on CTPA	RPA	RPA and LPA	RPA	RPA and LPA	RPA and LPA	RPA and LPA	LPA and Segmental PA	RPA and Segmental and sub segmental PA	Segmental PA	RPA and left descending PA	RPA and sub segmental artery	RPA and segmental artery
2D Echo	RA/RV dilated. Paradoxical septal motion	RA/RV dilated.	Moderate TR. Paradoxical septal motion	RA/RV dilated. Paradoxical septal motion	RA/RV Dilated.	RA/RV Dilated	RA/RV Dilated	NAD	RA/RV dilated.	RA/RV dilated	RA/RV dilated.	RA/RV dilated

Abbreviations: ABG-Arterial blood gas, BE-Base Excess, P/F ratio-Arterial partial pressure of oxygen divided by Fraction of inspired oxygen (FiO₂) in percentage, RPA-Right pulmonary artery, LPA-Left pulmonary artery, PA-Pulmonary artery, RA-Right atrium, RV-Right ventricle.

Fig. 1.

CTPA of a patient with acute pulmonary thromboembolism in the right pulmonary artery.

Fig. 2.

CTPA of a patient with acute pulmonary thromboembolism in the bilateral pulmonary artery.

Fig. 3.

CTPA of a patient with acute pulmonary thromboembolism in the segmental pulmonary artery.

Fig. 4.

CTPA of a patient with acute pulmonary thromboembolism in the subsegmental pulmonary artery.

HFNC use and patients evolution

All patients received HFNC oxygen therapy treatment for AHRF along with injectable low molecular weight heparin at the dose of 1 mg/kg every 12 hourly during the hospital stay. Initial HFNC settings were FiO₂ ranging between 0.9 and 1 and flow ranging between 50 and 60 L/Min. Respiratory parameters significantly improved after 1 h with the initiation of HFNC. Baseline initial low SpO₂ increase was in the minimum to maximum range of 92% to 96% (Median SpO₂ 94% and Mean SpO₂ 93.6% with SD 1.3) during therapy. PaO₂ in mm Hg increase was in the minimum to maximum range of 68 to 84 (Median PaO₂ 76 and Mean PaO₂ 75 with SD 5) on room air during therapy. The respiratory rate per minute reduction was in the minimum to maximum of 20 to maximum range of 24 (Median and mean respiratory rate 22.5 with SD 1.3) during therapy. Hemodynamic parameters did not show any significant variation after the initiation of HFNC. HFNC was applied for a duration of 6–10 days. No patient required intubation for AHRF. Thrombolysis was not administered to any patients as they remained hemodynamically stable. All were successfully weaned off from HFNC once they maintained the target SpO₂ with nasal prong oxygen (Less than 6 L/min oxygen requirement). All patients were given conventional oxygen therapy through nasal prong after 6–10 days of HFNC therapy. Finally, COT through nasal prong was also weaned off and all patients maintained target oxygen saturation at room air. All patients were discharged to home with oral anticoagulant therapy. In this retrospective series, we described HFNC oxygen therapy use in 12 PTE patients. Its prompt clinical efficacy was attested by improvement in oxygen saturation and decreased respiratory rate, as early as 1 h of HFNC use (Table 2).

Table 2.

Outcome of patients and effectiveness of Hfnc after one hour of therapy.

Features	Case 1	Case 2	Case 3	Case 4	Case 5`	Case 6	Case 7	Case 8	Case 9	Case 10	Case 11	Case 12
Respiratory Rate (Rate/Min)	22	22	24	22	24	24	22	24	23	21	22	20
SpO2(%)	93	94	95	92	94	92	94	92	96	95	94	93
Pa O2 (mm Hg)	72	76	80	68	76	68	76	68	84	80	76	72
Blood pressure (mm of Hg)	112/72	110/ 76	122/ 80	118/ 70	104/ 64	106/ 68	118/ 78	106/66	122/76	116/74	110/70	122/76
Heart Rate (beats/min)	94	92	98	96	96	96	94	93	91	90	92	95
Duration of HFNC provided (No of Days of therapy)	09	07	08	10	10	10	08	09	06	07	08	07
Discharged after number of days of hospitalisation	15 days	14 days	14 days	20 days	21 days	21 days	16 days	16 days	14 days	15 days	14 days	14 days

Discussion

High-Flow Nasal Cannula oxygen therapy has been used previously in various etiologies of acute hypoxemic respiratory failure. Our aim was to investigate the efficacy of HFNC therapy in patients of acute PTE who developed acute hypoxemic respiratory failure. There are numerous benefits of using HFNC in the treatment of patients with acute PTE and AHRF. COT will not be able to deliver the required FiO₂ and PEEP to AHRF patients in comparison with HFNC. The FiO₂ requirement for patients who need 6 L/min of oxygen on nasal prong with SpO₂ more than 92% approximately corresponds to 44%, and PaO₂/FiO₂ will be less than 300.³ Patients requiring oxygen support of more than 6 L/Min should be put on a face mask or non-rebreather mask.³ Application of a face mask is uncomfortable and challenging to the patient during feeding, as removing the face mask will compromise the oxygen requirement. HFNC oxygen therapy allows the patient to speak and feed without compromising FiO₂ requirements. Oxygen therapy by HFNC eliminates the complications related to noninvasive ventilation like air leaks, nasal trauma, skin lesions, pressure ulcers, and patient intolerance due to the delivery of high pressure. In acute PTE, the use of NIV escalates intrathoracic pressure. This may result in a decrease in right ventricular stroke volume and arterial pressure, which leads to NIV intolerance and NIV failure. Patients with acute PTE and AHRF get intubated due to NIV failure and leads to poor patient outcomes and prognosis. The use of HFNC improves oxygenation along with providing the essentially required airway pressure. This eludes the use of NIV and endotracheal intubation. HFNC provides a low level of positive end-expiratory pressure and offers washout of dead space ventilation in the upper airways. This helps in improving mechanical pulmonary properties of lungs and unloading inspiratory muscle effort of patients.⁶ HFNC decreases alveolar dead space and aids in the secondary enhancement of alveolar ventilation. HFNC oxygen therapy improves thoracoabdominal synchrony, lessening the work of breathing and reducing the breathing frequencies of patients with acute PTE who develops AHRF.⁸ Hence the findings of HFNC therapy in patients of AHRF with Acute PTE are quite fascinating. Detrimental hemodynamic effects related to HFNC are not seen and have not been reported. Oxygen therapy may be viewed as an epoch channel to autogenous fibrinolysis in patients of PTE. HFNC oxygen therapy helps to alleviate respiratory distress, and it provides time for natural primary fibrinolysis to occur.⁷ A rapid improvement in patient’s oxygenation and respiratory rate and consequently relief in respiratory distress was found in the patients when treated with HFNC. This alleviation of respiratory failure seems to be the hallmark of HFNC oxygen therapy and its efficacy.

Messika et al. analyzed 17 patients with severe acute PTE, and HFNC oxygen therapy was given for AHRF patients.⁷ In his study, three patients received thrombolysis, and two patients died. Their study concluded that respiratory parameters markedly improved after 2 h of therapy with HFNC without substantial differences in hemodynamic parameters. In their study, SpO₂ increased from 93% to 100%, and the respiratory rate reduced from 29 to 20 cycles per minute.⁷ Case report published by Alvarez et al⁹ buttresses the hitherto published data of Messika et al. Their case report proposed that HFNC oxygen therapy is a successful modality of treatment in patients with PTE, although the authors have also emphasized the need for more randomized clinical trials to evaluate the usefulness of HFNC in these patients.⁹ Lacroix et al. illustrated that HFNC oxygen therapy helps to maintain SpO₂ to an acceptable level in patients having PTE with AHRF. Their case report concluded that HFNC oxygen therapy aids in avoiding mechanical ventilation and provides time for therapeutic effects of anticoagulants to occur in patients with PTE.¹⁰ HFNC had been established to have not only medical benefits to the patients but also associated with increased patient comfort and relaxation. In a randomized crossover study, Mauri et al. found a higher amount of comfort and coziness level in patients treated with HFNC as compared to NIV.¹¹ An observational survey among ICU physicians to judge the effectiveness of HFNC oxygen therapy in clinical situations like PTE showed that AHRF was considered as a pertinent initial indication of HFNC.¹² The results of the survey showed that HFNC therapy was successful in 60% of patients in avoiding intubation.¹²

A meta-analysis of three databases, namely PubMed, Cochrane, and EMBASE, carried out to evaluate the effectiveness of HFNC oxygen therapy compared with COT and NIV for the treatment of AHRF showed that use of HFNC therapy in AHRF patients in emergency departments (EDs) would reduce the intubation rate compared with COT. In addition, the meta-analysis showed that HFNC oxygen therapy would reduce the need for escalation of the treatment regime.¹³ The use of HFNC therapy reduces the dyspnoea level and increases the patient’s comfort level compared with COT through a face mask or non-rebreathing mask.^13,14 Frat et al. (FLORALI study) showed that management with HFNC oxygen therapy improved the comfort and endurance rate among all observed 106 patients out of 310 patients with AHRF. The study also illustrated that HFNC oxygen therapy is superior and effective as compared with COT or NIV in patients with AHRF.¹⁵ In patients with AHRF, HFNC displayed manifold physiologic effects, including the reduction of inspiratory effort and decreased respiratory rate.¹⁶ HFNC also helps in the improvement of lung volume and lung compliance. These physiologic effects might inspire the clinical and practical effectiveness of HFNC.^16,17

Our study holds some limitations; The number of patients was small in this single-center study without a control arm. But one must bear in mind that patients with acute PTE with AHRF are not that frequent. There were no deaths probably due to prompt treatment, and none underwent thrombolysis, as all were hemodynamically stable after initiation of treatment. Our present retrospective study on the efficacy of HFNC oxygen therapy in patients of acute PTE with AHRF is promising as it has minimal missing data. A strength of our study is that it included a homogenous series of acute PTE with AHRF. Most had Bilateral PE, with paradoxical septum motion and profound hypoxemia with a mean Sp02 of 81%. All patients having acute PTE with AHRF were treated in our institute using HFNC oxygen therapy along with anticoagulants, and all patients survived.

Conclusion

HFNC use has been described in various situations of AHRF. Here we showed the efficacy of HFNC oxygen therapy in patients of acute PTE with acute hypoxemic respiratory failure from India. We found a rapid improvement in patient’s respiratory distress in terms of oxygenation and respiratory rate. This alleviation of dyspnoea in patients with acute PTE and AHRF seems to be the vital evidence and hallmark for the use of HFNC oxygen therapy and its efficacy. HFNC oxygen therapy can be implemented in the emergency department and intensive care unit, where a number of patients suffering from acute PTE with AHRF are managed. It facilitates a prompt improvement in respiratory parameters without any significant hemodynamic effect and providing a time frame for endogenous fibrinolysis. HFNC oxygen therapy is an effective modality for the treatment of patients with acute PTE and can be helpful in avoiding noninvasive and invasive ventilatory support. However, further randomized control trials are required to confirm its superiority over NIV.

Disclosure of competing interest

The authors have none to declare.