Airway Hygiene in COVID-19 Pneumonia: Treatment Responses of 3 Critically Ill Cruise Ship Employees

Background

In December 2019 the novel respiratory illness SARS-COV-2 broke out in Wuhan, China and rapidly spread across the globe, giving rise to the current COVID-19 pandemic. As of July 15, 2020, the World Health Organization (WHO) reported there were 13 150 645 confirmed cases throughout the world [1]. Although SARS-COV-2 largely manifests mild or nonexistent symptoms, rapid clinical deterioration can arise within the initial 2 weeks of illness [2]. Severe respiratory symptoms are associated with atypical pneumonia that can progress to acute respiratory distress syndrome (ARDS), although the pathogenesis is still being elucidated. COVID-19-related acute respiratory distress syndrome (ARDS) has been described and usually results in acute hypoxemic respiratory failure (AHRF) [3]. The incidence of COVID-19-related ARDS has ranged from 3.4% to 31% in hospitalized patients [4–8]. Timely endotracheal intubation and transfer to the ICU is critical in these cases. In a study of risk factors for COVID-19 mortality, ARDS was found to occur in 93% of patients who did not survive [8]. Interestingly, COVID-19-related ARDS does not directly resemble the “typical” ARDS due to other causes [3,9]. Therefore, treatment strategies for typical ARDS may not be as effective in COVID-19-related ARDS. The unique disease traits of COVID-19 pose unprecedented healthcare challenges, requiring strong research efforts and innovative drug repurposing strategies.

In the absence of a specific antiviral medication and vaccination, the tenets of current management have been preventive and supportive care. For cases of AHRF, high-flow nasal oxygen (HFNO) therapy can treat hypoxia and can avert the need for supportive mechanical ventilation [10]. Titration of HFNO to a target oxygen saturation (SpO2) of 90–96% along with a low threshold for endotracheal intubation has been advocated [11]. Recently, a multicenter study on COVID-19 outcomes in the New York City area reported that 320 of 2534 (12.2%) patients who were discharged alive or who died underwent supportive mechanical ventilation during their hospital course [12]. The mainstay of supportive mechanical ventilation in COVID-19 patients with AHRF is protective lung ventilation, which consists of a low tidal volume (≤6 mL/kg predicted body weight) and plateau pressure ≤30 cm H2O [11,13]. Patients with refractory hypoxemia may be considered for prone positioning, higher levels of positive end-expiratory pressure (PEEP), intravenous neuromuscular blocking agents, and extracorporeal membrane oxygenation (ECMO) [14]. Additionally, dexamethasone and high-dose vitamin C may help attenuate the aberrant inflammatory response in COVID-19-related ARDS [15,16]. A combination of treatments is needed to improve oxygenation and prevent clinical deterioration in critically ill patients with COVID-19.

An impressive distinction of COVID-19 pneumonia is the wide variability in disease progression and response to treatment. Gattinoni et al. suggested different phenotypes (Type-L and Type-H) according to lung elastance, ventilation to perfusion ratio, weight, and alveolar recruitability [17]. This corresponds with the amount of inflammatory response and consequent interstitial edema during pulmonary infection. Interestingly, postmortem studies on patients with a confirmed COVID-19 diagnosis have revealed extensive pulmonary mucous secretions and plugging [18,19]. Liu et al. described thick and sticky secretions in the trachea, bronchus, and alveoli in an autopsy with COVID-19 confirmed as the cause of death [20]. In accordance with these observations, stringent pulmonary hygiene management may be needed to optimize oxygen supplementation.

To the best of our knowledge, the role of pulmonary hygiene management in critically ill patients with SARS-COV-2 pneumonia has been largely overlooked in recent research. For the purpose of this case series, pulmonary hygiene management refers to mucolytics, bronchodilators, and tracheal suctioning. The utility of mucolytics, bronchodilators, and tracheal suctioning on the prevention of hospital-acquired pulmonary infections and mortality in the Intensive Care Unit (ICU) has been well studied in the past [21]. With the exception of bromhexine hydrochloride, a well-known mucolytic cough suppressant, research on modalities that improve mucus clearance in COVID-19 pneumonia is limited. The current report describes 3 cases of COVID-19 pneumonia, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing from nasopharyngeal swabs, in critically ill cruise ship employees who developed ARDS and required supportive mechanical ventilation (Table 1). In this article, we explore the role of a therapeutic strategy consisting of inhaled albuterol, inhaled ipratropium, inhaled n-acetylcysteine, and routine tracheal suctioning in COVID-19 pneumonia and ARDS.

Case Reports

CASE 1:

A 72-year-old male cruise ship employee with a past medical history of coronary artery disease, chronic kidney disease, diabetes mellitus type II, and hypertension was brought to the Emergency Department (ED) with 5 days of worsening shortness of breath, dry cough and fever. In the 2 days prior to hospital admission, the patient received amoxicillin-clavulanic acid, azithromycin, and oseltamivir on the cruise ship, without improvement. At the time of hospital admission, the patient was dyspneic with an oxygen saturation (SpO2) of 82% on room air. ABG values revealed pH 7.37, PaO2 46.2, PCO2 29.3, HCO3 16.4, and SO2 83 on a nasal cannula. The initial chest X-ray (CXR) is illustrated in Figure 1A. A nasopharyngeal specimen was collected in the hospital and was confirmed to be COVID-19-positive by our laboratory. Blood lab results demonstrated an elevated white blood count (13.10) and neutrophil percentage (91.2%) along with decreased lymphocyte percentage (5.3%) in the Emergency Department. For the most part, vitals were within normal limits with the exception of respiratory rate; blood pressure (BP) 136/68 mmHg, pulse (HR) 95 beats per min respiratory rate (RR) 25 breaths per min temperature (TEMP) 37.8°C. The patient was put on a non-rebreather mask but continued to be restless and had difficulty forming full sentences. Despite initiation of non-invasive ventilation, he did not surpass 88% SpO2. Consequently, the patient underwent endotracheal intubation and a nasogastric tube was placed. Initial ventilator settings in the ICU were tidal volume (TV) 500 mL per inspiration, fraction of inspired oxygen (FiO2) 50%, respiratory rate (RR) 12 breaths per min (bpm), and PEEP 5 titrated to 8 cmH20. We administered subcutaneous heparin 5000 U every 8 h, oral azithromycin 250 mg every day, intravenous dexamethasone 12 mg every 6 h, oral hydroxychloroquine 400 mg every 12 h, oral vitamin C 1000 mg every day, and oral guaifenesin 600 mg every 6 h. During inhalation therapy, a closed circuit was maintained by depositing the metered-dose inhaler aerosol through a spacer device connected to the ventilator. Breathing treatments consisted of inhaled levalbuterol 1.25 mg every 6 h, inhaled ipratropium 0.5 mg every 6 h, and inhaled n-acetylcysteine 200 mg every 6 h. Prior to breathing treatments, tracheal suctioning was performed to remove secretions. Throughout his hospital course, the patient encountered numerous complications. He developed septic shock resulting in acute kidney failure and severe hypotension, which required emergent dialysis and titrated norepinephrine bitartrate. Additionally, multiple transfusions of packed red blood cells were administered for an acute gastrointestinal hemorrhage. These conditions improved by following the Kidney Disease Improving Global Outcomes (KDIGO), American College of Gastroenterology (ACG), and Surviving Sepsis Campaign clinical practice guidelines. The CXR completed on day 14 of treatment is shown in Figure 1B. On day 24 of hospitalization, the patient was extubated. At that time, he was downgraded from ICU status and remained on a venturi mask with oxygen saturation of 94–92%. At day 30 of hospitalization, he was still alive.

CASE 2:

A 65-year-old male cruise ship employee with a past medical history of diabetes mellitus type II presented to the ED with 3 days of chest tightness, shortness of breath, fever, and diarrhea. Upon arrival to the ED, the patient was severely dyspneic and unable to form full sentences. A non-rebreather mask was immediately placed because he was displaying these signs of respiratory distress. ABG values revealed pH 7.46, PaO2 57, PaCO2 35, HCO3 24, and SO2 91.1 on a non-rebreather mask. Vitals were within normal limits with the exception of respiratory rate; BP 123/65 mmHg, HR 94 bpm, RR 28 bpm, and TEMP 36.8°C. The initial chest X-ray (CXR) is shown in Figure 2A. Laboratory results from blood drawn on admission demonstrated an elevated white blood cell count (14.3) and neutro-phil percentage (84.1%), as well as a decreased lymphocyte percentage (6.3%). A nasopharyngeal specimen was collected and confirmed to be COVID-19-positive by the hospital laboratory. Although a non-rebreather mask was placed, he continued to be restless and dyspneic, and his SpO2 decreased to 88%. The patient was transferred to the ICU and underwent endotracheal intubation as well as placement of a nasogastric tube. Initial ventilator settings in the ICU were TV 500 mL per inspiration, RR 12 bpm, fraction of inspired oxygen (FiO2) 70%, and PEEP 6 cmH20. He received subcutaneous heparin 5000 U every 8 h, oral azithromycin 250 mg every day, intravenous dexamethasone 12 mg every 6 h, oral hydroxychloroquine 400 mg every 12 h, oral vitamin C 1000 mg every day, and oral guaifenesin 600 mg every 6 h. Additionally, we administered inhaled levalbuterol 1.25 mg every 6 h, inhaled ipratropium 0.5 mg every 6 h, and inhaled n-acetylcysteine 200 mg every 6 h. Tracheal suctioning was performed routinely, prior to medication administration. On day 1 in the ICU, the patient became hemodynamically unstable, requiring 3 days of titrated norepinephrine bitartrate. Over the following week, he remained hemodynamically stable and his respiratory status improved. On day 10, the patient was successfully extubated and started on non-invasive positive-pressure ventilation (NIPPV). The patient was comfortable and breathing well on the NIPPV and was weaned off supplemental oxygen. On room air, his SpO2 was 93.1% (day 11). Figure 2B illustrates his CXR on day 14 of treatment. Throughout the remainder of his hospital course, the patient sparingly used the nasal cannula provided. His discharge was delayed until day 39 for reasons outside the control of the physician and hospital.

CASE 3:

A 48-year-old male cruise ship employee without any relevant past medical history was brought to the ED with 7 days of worsening fever, dry cough, and shortness of breath. Upon arrival to the ED, he was anxious, restless, and dyspneic. ABG values revealed pH 7.51, PaO2 42.8, PaCO2 37.4, HCO3 29.6, and SO2 83 on a nasal cannula. The patient was immediately placed on a non-rebreather mask, which led to a marked improvement in SpO2 (93%) and his ability to breathe comfortably. In the ED, he had an elevated blood pressure, heart rate, and respiratory rate; BP 155/85 mmHg, HR 108, RR 28, TEMP 37.2°C. The initial CXR is shown in Figure 3A. Laboratory results from blood drawn in the ED demonstrated the white blood cell count was within normal limits (7.55), decreased lymphocyte percentage (8.9%), and increased neutrophil percentage (80.4%). The patient was admitted to the ICU on a non-rebreather mask. We administered subcutaneous heparin 5000 U every 8 h, oral azithromycin 250 mg every day, intravenous dexamethasone 12 mg every 6 h, oral hydroxychloroquine 400 mg every 12 h, oral vitamin C 1000 mg every day, and oral guaifenesin 600 mg every 6 h. In addition, he received inhaled levalbuterol 1.25 mg every 6 h, inhaled ipratropium 0.5 mg every 6 h, and inhaled n-acetylcysteine 200 mg every 6 h. Tracheal suctioning was performed prior to medication administration. The patient maintained the targeted SpO2 (95–93%) on a non-rebreather mask until day 5 of hospitalization. At that time, he abruptly desaturated to an SpO2 of 43% and emergent endotracheal intubation was immediately performed. Titrated norepinephrine bitartrate was started for hemodynamic instability. Ventilator settings were TV 500, FiO2 100%, RR 20, and PEEP 14. Shortly thereafter, his SpO2 improved to 93%. After 9 days of supportive mechanical ventilation, his respiratory status improved, and he was extubated. A CXR from hospital day 14 is illustrated in Figure 3B. Throughout the remainder of the hospital course, the patient remained on nasal cannula with SpO2 ranging between 98–93%. He was discharged from the hospital on day 41.

Discussion

LIMITATIONS:

Our findings were limited to 3 patients in a single community hospital intensive care unit (ICU). In all 3 cases, the patients were administered multiple medications according to popular treatment strategies at that time. Hydroxychloroquine, azithromycin, and dexamethasone have been proposed to improve outcomes in patients with COVID-19. At present, the efficacy of hydroxychloroquine and azithromycin is uncertain and has become a topic of fervent debate. Conversely, dexamethasone has been shown to improve mortality in severely ill patients with COVID-19 [15]. In addition, older age (65 years and above) and comorbid conditions is an indicator of poor prognosis in severe cases [53]. One of the patients mentioned in this case series was under the age of 65 years, which may have contributed to a better outcome.

Conclusions

This case series highlights the importance of pulmonary hygiene management in mechanically ventilated patients with COVID-19 pneumonia and ARDS. Our pulmonary hygiene strategy consists of mucolytics, bronchodilators, and routine tracheal suctioning. Inhaled medications were administered through a metered-dose inhaler (MDI) in line with a closed ventilator circuit. Implementation of this pulmonary hygiene strategy may prevent acute complications in the ICU as well as long-term sequelae after hospital discharge. All 3 critically ill patients in the present study were extubated, downgraded from ICU status, and reached 30-day survival.