The Use of Intermittent Non-Invasive Ventilation as an Alveolar Recruitment Method for Patient with Severe COVID-19 Pneumonia
Mazen Zouwayhed1, *, Saria Gouher2, Balu Bhaskar1, Moeena Zain2, Samer Burghleh2, Rania Khani3, Razan Yousef2, Abdul Rahman Khan2, Naim Aoun1
1 Department of Pulmonary/ Critical Care, American Hospital Dubai, Dubai, UAE
2 Department of Internal Medicine, American Hospital Dubai, Dubai, UAE
3 Department of Pharmacy, American Hospital Dubai, Dubai, UAE
The use of non-invasive ventilation (NIV) as a therapy for acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia has been controversial. NIV is an aerosol generating procedure which may increase the risk of viral transmission amongst patients and staff. Because of fear of aerosolizing the virus and transmitting the disease, initial expert recommendation was to avoid NIV and proceed with early intubation. With further experience of the virus, this recommendation has been challenged and NIV has been used widely with some retrospective studies quoting between 11 to 56 percent of COVID-19 related respiratory failures being treated with NIV.
The objective of this study is to assess the efficacy and safety of using non-invasive mechanical ventilation as an alveolar recruitment method for patients with severe COVID-19 pneumonia. This method was used by our respiratory team on selected patients during the early phase of the COVID-19 pandemic.
We reviewed the charts of patients that were admitted to the American Hospital Dubai intensive care unit, or our medical step-down unit who had diffuse bilateral infiltrates requiring oxygen supplementation between March and October 2020. We identified patients who were on intermittent BiPAP in addition to standard care. We also monitored the rate of infection among staff taking care of these patients.
Average length of stay after starting BIPAP therapy was 6.8 days, while the average total length of stay was 13.6 days. Only one patient was transferred to the ICU after being on the BIPAP protocol and did not need intubation. All patients were discharged home either without oxygen or with their chronic baseline home oxygen requirement. Radiological improvement in aeration was seen in 100% of patients at follow-up x-ray post-intervention. There were no reported pulmonary complications from barotrauma, such as pneumothorax or pneumomediastinum. There were no reported cases of staff infection to the health care workers that were taking care of these patients.
Our first of its kind observational study showed clearly that using BIPAP therapy for one hour three times daily during nebulization therapy in addition to standard care resulted in a significant reduction in hospital length of stay and hastened the clinical and radiological improvement of patients with severe COVID-19 pneumonia.
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* Address correspondence to this author at Department of Pulmonary/ Critical Care, American Hospital Dubai, Dubai, UAE; Tel: 0545011075; E-mail: firstname.lastname@example.org
COVID-19 was initially recognized as an emerging disease in China in December 2019 which rapidly spread to become a public health emergency [1, 2]. Disease severity is variable with more severe infections occurring in 14% of cases and critical cases occurring in approximately 5% of cases [1, 2]. Disease progression leads to acute respiratory failure and in some cases ARDS. Patients with severe and critical disease that develops acute respiratory failure often require mechanical ventilation, which data consistently shows that it carries associated high mortality [3-8].
The use of non-invasive ventilation (NIV) - which includes both Bi-level Positive Airway Pressure (BiPAP) and Continuous Positive Airway Pressure (CPAP)- for the therapy of ARDS secondary to COVID-19 has been controversial. Early in the pandemic, experts recommendation was to avoid NIV and proceed to early intubation if the patient required over 6 L/min with refractory hypoxemia or increased work of breathing [9, 10]. This was recommended on the basis that the efficacy of NIV was unclear in this novel virus and many patients proceeded to mechanical ventilation when reaching the parameters mentioned above. As NIV is classed as an aerosol generating procedure, the additional risk was to staff and nearby patients with regards to aerosol mediated disease transmission [9, 10]. As experience developed, this recommendation was increasingly challenged as the documented efficacy in improvement of mortality and reduction in intubation grew [11, 12]. The avoidance of proceeding to mechanical ventilation was particularly attractive due to the anticipated avoidance of the many complications associated with invasive positive pressure ventilation (IPPV) in this patient group . During the second wave, there was an increased utilization of both high flow nasal canula and non-invasive ventilation, reserving intubation and ventilation for those who continued to deteriorate despite non-invasive techniques. Adoption of early non-invasive techniques varied but some studies showed that 11 to 56 percent of COVID-19 related respiratory failure was treated with NIV .
Recruitment maneuvers are now used as a salvage therapy for the patients suffering from acute respiratory failure due to ARDS [15, 16]. The positive pressure used during the recruitment maneuver is thought to improve aeration to the diseased alveoli and improve oxygenation . Application of recruitment maneuver with non-invasive ventilation has never been studied, although there is some evidence that the use of non-invasive ventilation results in improved tidal volumes [17-19].
In our pioneering observational study, we tried to evaluate the effectiveness of using non-invasive ventilation as a recruitment tool. In addition to this, we also aimed to enhance nebulized medication delivery into the alveoli by placing the patients on periods of non-invasive mechanical ventilation when receiving nebulized medications. This method was used by our pulmonary critical care team in the early stage of the COVID-19 pandemic as a salvage therapy for patients who were not improving on standard therapy both early and late in their disease course.
We reviewed the charts of patients that were admitted to the American Hospital Dubai intensive care unit or our medical step-down unit. We included patients with diffuse bilateral pulmonary infiltrates and a supplemental oxygen requirement between March and October 2020.
We identified 15 patients who, in addition to the standard care provided by their primary team, were placed on BIPAP (Setting IPAP 10-15, EPAP 5-6 cmH2O) for 1 hour 3 times daily while they received their nebulized medications. We excluded those patients who were on continuous non-invasive mechanical ventilation due to acute respiratory failure. The use of NIV for short periods during the day was expected to result in better gas exchange and we postulated that we could achieve better delivery of the nebulized medications deep into the lungs for a patient with severe COVID-19 pneumonia.
Importantly we also monitored the number of infected staff to insure that the use of BIPAP did not result in increased staff infection (as this was one of NIVs main criticisms).
We used non-fenestrated BIPAP masks to reduce the risk of aerosolization of the virus during the maneuver.
2.1. Patient Population
15 patients were included between March and October 2020 (Table 1). At baseline and before starting the BIPAP therapy, all patients were categorized as having severe disease as per the COVID-19 severity scale .
Baseline x-ray showed bilateral ground glass opacities involving > 50% of the lung fields in 11/ 15 patients (73%) and involving 25-50% of the lung fields in 4/15 patients (26%) as reported by an independent radiologist not aware of the study intervention (Table 2).
Baseline laboratory findings include average WBC count 9500 Cell/ ml, average D-Dimer 922.9 ng/ ml, average Ferritin 1451.2 ug/L, Average CRP 91.5mg/L, average procalcitonin 1.5 ng/ml.
Labs and X-ray findings.
X-ray Ground glass opacity
- > 50% of the lung fields in 11 patients (73%) - 25-50% of the lung fields in 4 Patients (26%)
9500 Cell/ ml,
922.9 ng/ ml
Labs and X-ray findings.
Average fraction of inspired oxygen at baseline was (FIO2) was 0.52. 6 / 15 (40%) required 5-8 L nasal cannula (NC), 4/15 (26%) required 2-4 L NC, 2 /15 (13%) required 50% via a venturi mask, 2/15 (13%) were on 100% oxygen via a non-rebreathing mask and 1/15 (6%) patient required 60L/100% high flow oxygen.
2.2. Medication Therapy
All patients received corticosteroids intravenously. 13 /15 (86%) received methylprednisolone 40 mg Q8H and 2 /15 (13%) received dexamethasone 8mg daily.
All patients were receiving IV antibiotics. 12/15 (80%) received Piperacillin / Tazobactam, 2/15 (13%) received levofloxacin and 1/15(6%) received azithromycin plus ceftriaxone. The use of antibiotics was popular during the period of the pandemic, where it was difficult to differentiate between COVID-19 pneumonia and other types of bacterial pneumonia.
Inhaled medications included Budesonide 1-2 mg nebulization twice daily in 14/15 patients (93%) and salbutamol/ ipratropium nebulization 3 times daily in 14 /15 patients (93%).
No COVID-19 specific medications were used on any of the study participants as they were not available at our facility at the time of the study (Table 3).
Patients included in the study received the study protocol at varying times from admission as inclusion was dependent on disease severity/progression. We included only patients who agreed to use the BIPAP and were able to tolerate the BIPAP therapy for at least 1 hour, 3 times daily. Data were collected retrospectively by reviewing the charts of the patient's post-discharge.
Average length of stay after starting BIPAP therapy was 6.8 days, while the average total length of stay was 13.6 days. (Mean LOS +/- SD)
There were no reported complications related to the use of non-invasive mechanical ventilation, specifically there were no GI complications (such as vomiting) and no reported barotrauma related complications such as pneumothorax. There were no reported deaths. All patients were discharged without any oxygen supplementation other than one patient who were discharged on their baseline home oxygen. Three patients had visits to the emergency department post discharge. There were no readmissions.
All patients had a repeated chest x-ray carried out approximately 3 to 6 days after starting the BIPAP therapy. 100% of patients showed radiologically improved aeration. There were no reported cases of staff becoming infected with COVID-19 (Table 4).
Table 4 Results.
Average length of stay after starting BIPAP
6.8 days (6.8 ±2.6)
Total average length of stay
13.6 days(13.6 ± 5.4
Requirement of ICU transfer
1 patient (6%)
Number of deaths
Patients discharged on O2
Visit ED post discharge
Barotrauma or pneumothorax
Reported staff infection
Table 4 Results.
During the initial phase of the COVID-19 pandemic, it was difficult to standardize therapy for patients who were deteriorating with multiple methods and different medications. It was very popular at that time to use antibiotics due to the difficulty in differentiating between viral and/or bacterial pneumonia related to COVID-19. Our pulmonary critical care team at American Hospital Dubai decided to use BIPAP therapy as an added therapy for patients who were deteriorating or not improving on standard therapy for COVID-19 pneumonia. Non-invasive ventilation has always been used as a salvage therapy to try and avoid or delay intubation in patients with acute respiratory failure. Similarly, recruitment manoeuvres have always been used for patients who are on mechanical ventilation, and have severe respiratory failure with associated severe hypoxemia. The use of non-invasive mechanical ventilation as a tool for recruitment of functional alveoli has never been studied in the past. This intervention combines BIPAP with nebulized medication. The effect of the positive pressure produced by the NIV was expected to recruit some of the diseased alveoli and to enhance medication delivery into the alveoli. We think that the positive pressure ventilation produced by the BIPAP machine caused alveolar recruitment which resulted in better alveolar aeriation and better gas exchange. The improved gas exchange in turn reduced the need for oxygen supplementation and the progression to invasive mechanical ventilation. The improved respiratory mechanics produced by the intermittent NIV resulted in faster clinical and radiological improvement which resulted in lower hospital length of stay. Although there was no specific control group for comparison, we believe that the use of intermittent BIPAP was helpful in hastening the recovery of these patients and shortening their length of stay. Discharging the patient early out of the hospital to their community environment shortens their recovery time and prevents other causes of nosocomial morbidity and infection, deconditioning and muscular weakness.
The study also showed that the use of BIPAP for patients with COVID-19 pneumonia is safe for both patients and the staff members with no reported staff infections. These findings provide further evidence that proceeding to early intubation and mechanical ventilation may not be required. The use of BIPAP wisely and in selected severe COVID-19 infection using a non-fenestrated BIPAP mask was not only safe and tolerable but also helpful in preventing patient deterioration.
The major strength of this study is that it is the first study to evaluate the use of non-invasive mechanical ventilation as a recruitment method rather than a salvage therapy for the patient with respiratory distress due to COVID-19 pneumonia. Non-invasive mechanical ventilation has always been used as a step-up therapy in the management of respiratory failure after supplemental oxygen fails but was never used as adjunctive therapy to prevent deterioration.
The limitation of our study is that it was a small observational study using chart review only and not a randomized control trial which would likely be unfeasible. Numbers and data collection were limited due to the manpower utilisation dealing with the pandemic crisis. This prevented us from having a desired comparative group with standard care only.
We believe that the utilisation of intermittent NIV early on in the severe COVID-19 disease course, in addition NIV facilitated nebulisation, results in faster clinical improvement and reduces the in-hospital length of stay. We believe that a larger study that includes a control group for comparison to validate those findings observed in our pioneering observational study is warranted to validate our findings.
This observational study demonstrated that using BIPAP therapy for 1 hour, three times daily during nebulization therapy in addition to standard care resulted in a significant reduction in hospital length of stay and hastened the clinical and radiological improvement of patients with severe COVID-19 pneumonia. The intervention has resulted in less deterioration and indeed, there were no reported deaths or the need for mechanical ventilation among study participants. There were no signs of barotrauma like pneumothorax or pneumomediastinum as a result of BIPAP use. Importantly there was seemingly no increased risk to staff contracting COVID-19 whilst looking after patients using this non-invasive modality.
LIST OF ABBREVIATIONS
= Bilevel Positive Airway Pressure
= Non-Invasive Positive Pressure Ventilation
= Non-Invasive Positive Pressure Ventilation
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
This study was approved by the ethics committee of the American Hospital Dubai.
HUMAN AND ANIMAL RIGHTS
No animals were used in this research. All human research procedures were followed in accordance with the ethical standards of the committee responsible for human
experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2013.
CONSENT FOR PUBLICATION
STANDARDS OF REPORTING
STROBE guidelines and methodologies were followed for this study.
AVAILABILITY OF DATA AND MATERIALS
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
Special acknowledgment to the respiratory therapy team at American hospital Dubai who provided non-invasive mechanical ventilation for COVID-19 patients.
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Abdullah Shehab Emirates Cardiac Society Emirates Medical Association Dubai (United Arab Emirates) Biography
Biography of Abdullah Shehab
Dr. Abdullah Shehab has 22 years of experience in Internal medicine, cardiology and interventional cardiology and medical education. Currently, he serves as the General Secretary of Emirates Cardiac Society and Vice President of Gulf Intervention Society. He is a Fellow of royal college of physicians UK, American college of physician, European society of cardiology, American college of cardiology, American society of cardiac intervention and fellow of the American heart association. Professor Shehab is the Chief Editor of Emirates Medical Journal and also serves as Editor in many other regional and international journals. Dr. Shehab has published 149 paper in Medline. His research interest includes: Heart failure, Coronary artery disease, Dyslipidaemia, Hypertension, Arrhythmias, Cardiac intervention, Cardiac imaging, Screening for cardiac disease in sport players, cardiovascular disease in pregnancy.