The Successful Use of Extracorporeal Membrane Oxygenation in a Newly Diagnosed HIV Patient with Acute Respiratory Distress Syndrome (ARDS) Complicated by Pneumocystis and Cytomegalovirus Pneumonia: A Case Report

Abstract

Background: We report a case of an adult patient with newly diagnosed human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), and acute respiratory distress syndrome (ARDS) secondary to pneumocystis and cytomegalovirus pneumonia that were present on presentation, which were successfully managed with venovenous extracorporeal membrane oxygenation (VV-ECMO). Case Presentation: A 40-year-old patient with a past medical history of asthma was admitted to a local hospital due to dyspnea, cough, and wheezing, where the patient was diagnosed with HIV infection, ARDS, and combined pneumocystis and cytomegalovirus pneumonia. Their pulmonary function quickly declined, necessitating mechanical ventilation (MV). After all conventional therapies failed, the patient was transferred to a tertiary medical center for VV-ECMO therapy. The patient was successfully treated with antiretroviral therapy (ART), antibiotics, antivirals, steroids, and 48 days of VV-ECMO support, with complete resolution of their respiratory symptoms. The patient was discharged on hospital day 82. Conclusions: HIV-positive patients with ARDS that is complicated by opportunistic pulmonary infections can be successfully managed with ART, appropriate anti-infective therapies, and VV-ECMO.

1. Introduction

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is often used as a form of rescue therapy for patients with acute respiratory distress syndrome (ARDS) despite maximal mechanical ventilation. VV-ECMO has gained popularity over the past 15 years as a successful treatment modality for ARDS due to the 2009 influenza (H1N1) pandemic and the ongoing COVID-19 pandemic [1]. An immunocompromised status has traditionally been regarded as a contraindication for VV-ECMO in ARDS given the poor outcomes in this subset of patients [2,3]. Currently, the evidence remains limited to case reports and small case series regarding VV-ECMO use in patients with ARDS secondary to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) who have failed to improve with optimal mechanical ventilation. Respiratory failure remains the most common cause of ICU admission in HIV/AIDS patients, with bacterial pneumonia and Pneumocystis jirovecii pneumonia (PJP) being the most common etiologies [4]. Since the use of invasive ventilation is an independent predictor for poor outcomes in HIV/AIDS-related ARDS patients, especially those with PJP [5], VV-ECMO has been emerging as an alternative avenue of treatment. The majority of the available literature describes the successful use of ECMO in HIV/AIDS patients with PJP-associated ARDS [6]. Our case report demonstrates the successful use of VV-ECMO in a previously untreated HIV/AIDS patient with ARDS due to PJP and cytomegalovirus (CMV) pneumonia, who achieved a full clinical recovery after adequately improving their immune system and treating the PJP and CMV.

2. Case Report

Initial presentation: A 40-year-old patient with a past medical history of asthma, who presented to an outside hospital with a 3-week history of coughing, wheezing, and dyspnea, was found to have extensive bilateral ground glass opacities on the CT scan and X-ray of the chest (Figure 1 and Figure 2). Admission testing revealed the patient to be HIV-positive with a CD4 count of 9 cells/mL and a viral load of 20,800. Additionally, the patient tested positive for P. jirovecii via direct immunofluorescence on admission, for which the patient was treated with trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone. Despite ongoing treatment, the patient’s clinical status continued to decline, necessitating mechanical ventilation on hospital day 10. At this time, the patient underwent bronchoalveolar lavage, which was positive for cytomegalovirus by polymerase chain reaction testing, in addition to serum-positive CMV (viral load of 175,000), for which ganciclovir was initiated and maintained for 11 days. The PCR test of BAL was also positive for CMV, suggesting CMV pneumonia. Unfortunately, the patient progressed into ARDS refractory to lung-protective ventilation, prone positioning, and inhaled nitric oxide.

Transfer of care: The patient was transferred to our facility for evaluation for ECMO on hospital day 18 (8 days after intubation). At the time of transfer, the arterial blood gas analysis showed hypoxia (PaO₂ of 79 mm Hg) on 100% fraction of inspired oxygen (FiO₂), Bi-level with P high/P low (30/1 cmH₂O), and T high/T low (3/0.6 sec). It is worth noting that the patient was not able to promptly receive antiretroviral therapy (ART) upon diagnosis of HIV in the setting of ileus due to poor enteral absorption and acute kidney injury. ART with abacavir, lamivudine, and dolutegravir was immediately started on ECMO day 1 when the symptoms of ileus began to resolve.

ECMO course: The patient’s respiratory status failed to improve due to maximal ventilator setting with volume control under the setting of tidal volume 6 mL/kg, FiO₂ 100%, positive end expiratory pressure (PEEP) 14, which suggested poor pulmonary compliance due to PJP and CMV pneumonia. Due to the failure to improve the respiratory condition, VV-ECMO was initiated via a 28-French dual-lumen catheter placed into the right internal jugular vein under transesophageal echocardiography. The initial circuit settings were a flow of 4.3 L/min, sweep gas 5.5 L/min, on an FdO₂ (fraction of delivered oxygen) of 100%. The mechanical ventilator settings were adjusted to pressure control with a pressure difference of 10, PEEP of 10, respiratory rate (RR) of 10, and FiO₂ of 40%. It is worth noting that the patient did not require a significant amount of inotropes or vasopressors during the ECMO course.

The VV-ECMO settings were titrated to a goal flow of 4–6 L/min, mean arterial pressure of 65–85 mmHg, mixed venous oxygen saturation on drainage cannula of 65–75%, and a PaO₂ > 50 mmHg until the patient began to have significant respiratory contribution with tidal volumes > 200 mL on day 30 of ECMO support. During ECMO day 33 to 36, the ECMO flow and sweep were weaned from 4.5 to 3 LPM and 5 to 0.5, respectively, as the patient was taking adequate tidal volume and showing signs of respiratory recovery. However, the patient progressively required more ECMO support from ECMO day 37 to 41. Repeat PCR testing for CMV showed an increase in the viral load to 18,000 from 1290. IV ganciclovir was re-initiated on ECMO day 41. The patient’s respiratory function markedly improved thereafter, allowing for the successful weaning of ECMO within the next 5 days. The patient was eventually decannulated from VV-ECMO on ECMO day 48 and maintained adequate ventilation on pressure support via tracheostomy. The patient continued to make clinical progress following VV-ECMO decannulation and was discharged to an acute inpatient rehabilitation facility on hospital day 82. ART was maintained throughout the hospitalization, and the CD 4 count and HIV viral load improved from 9 to 38 and 20,800 to <20 at discharge, respectively.

Other events during hospital stay: It is worth nothing that the patient’s clinical course had several complications. First, the patient developed recurrent bilateral pneumothoraces requiring pigtail placement for 12 days, which eventually resolved completely. The patient was also found to have VRE bacteremia with no evidence of endocarditis on the echocardiogram, which was first treated with 3 weeks of linezolid and then with 6 weeks of daptomycin. Finally, there was a very small subarachnoid hemorrhage that was thought to be due to the disruption of the cerebral autoregulation, which was managed for a brief cessation of systemic anticoagulation for 2 days. The repeat CT scan showed a stable size of the subarachnoid hemorrhage.

3. Discussion

The exponential increase in the use of VV-ECMO, starting with the H1N1 pandemic in 2009, became more evident during the COVID-19 pandemic. VV-ECMO can alleviate the burden of mechanical power from mechanical ventilation, thereby reducing the incidence of ventilator-induced lung injury, which is frequently seen in patients with ARDS. However, VV-ECMO is a resource-intensive therapy with high costs and is associated with life-threatening complications such as thrombosis, coagulopathy, infection, and brain injury. There are no clear guidelines established for the use of VV-ECMO in HIV/AIDS patients with severe ARDS. The currently available ECMO guidelines state that an immunocompromised status is considered as a relative contraindication because of high mortality—the overall 6-month survival was only 30%, and immunosuppression was an independent risk factor for mortality in the prognosis scoring system used for respiratory failure in ECMO [7,8]. To this date, only case reports and small case series have reported the successful use of VV-ECMO to treat refractory ARDS in HIV/AIDS patients. It is important to note that the majority of the case reports (11 out of 14) describe the use of VV-ECMO in HIV/AIDS-related ARDS due to PJP [6]. Our patient had untreated HIV with PJP and concomitant CMV pneumonia, and their respiratory function was fully recovered after treating the CMV pneumonia. The patient’s respiratory function, previously not improving despite prolonged VV-ECMO therapy and adequate medical treatment of PJP, finally turned the corner after treating the CMV pneumonia.

A retrospective study of 147 patients with HIV infection suggests that an infectious etiology accounts for 78% of the causes of acute respiratory failure. Bacterial pneumonia and PJP were the two most common infectious etiologies, with 50% and 35%, respectively [4]. In addition, 3% of the patients experienced acute respiratory failure due to opportunistic pneumonia secondary to cytomegalovirus [4]. The incidence of full-blown respiratory failure due to CMV is very rare and limited to case reports [9]. To our knowledge, the successful use of VV-ECMO in such a patient is limited to only one case report [10].

The incidence of CMV pneumonia in HIV patients is rare and reported to be 5–8% [11]. The mainstay of treatment for CMV infection in an HIV patient is the restoration of the immune system with ART [12]. Even though our patient received ganciclovir treatment upon the diagnosis of CMV pneumonia in the beginning of the hospital course, the patient’s immune function was not adequately restored to fight against CMV, as the ART was delayed due to ileus and poor enteral absorption. Although the diagnosis of PJP was quickly made and immediately treated with a high dose of TMP/SMX for 21 days and steroids, the respiratory function failed to improve, resulting in continuous support on VV-ECMO. The CMV viral load, which initially responded appropriately after initial ganciclovir treatment, was shown to be elevated again when the patient had an acute hypoxic episode requiring higher ECMO support around hospital day 55 (ECMO day 40). The CD4 count was less than 50 cells/mm3 at this time. Although the HIV viral load during this time was lower than 20, the patient’s CD4 count was less than 30, suggesting incomplete restoration of immune system (Figure 3). As a result, the patient had an opportunistic infection with CMV pneumonia, as supported by the increase in the CMV viral load (Figure 4). As the 2-week course of ganciclovir treatment was re-initiated, the patient began to pull better tidal volumes and required less VV-ECMO support, leading to successful decannulation within the next 7 days.

We believe that the patient’s ARDS was caused by both PJP and CMV pneumonia rather than immune reconstitution inflammatory syndrome (IRIS). IRIS is unlikely in this patient, because the timing of the acute respiratory deterioration episode did not correspond with the immune recovery. Also, an IRIS-associated Pneumocystis jirovecii infection usually presents after 1–3 weeks of ART [13], whereas our patient experienced this episode 6 weeks after ART. The treatment of CMV pneumonia resulted in an obvious improvement in the pulmonary function, which previously failed to achieve full recovery despite a complete course of PJP treatment.

Despite the absence of well-established guidelines, our case report clearly suggests that VV-ECMO should be considered, even in treatment-naïve HIV/AIDS patients with persistent ARDS despite mechanical ventilation, corroborating the findings in the recent systematic review and individual patient data analysis (n = 29, 22 studies), which demonstrated that ECMO support was used successfully in 93% of patients [14]. Thorough work-up and diagnosis of the etiologies of ARDS should be completed to ensure prompt initiation of the appropriate treatment. Also, rare causes of opportunistic infections causing ARDS should be explored when a patient’s respiratory function is not progressing despite conventional management.

4. Conclusions

The management of ARDS in HIV/AIDS patients is challenging. Immediate ART should be initiated, in addition to promptly identifying the causative organisms and appropriate targeted treatment. As our case and recent case reports suggest, VV-ECMO can be a viable treatment modality for ARDS related to HIV/AIDS complications. Clinicians should consider it as an alternative option for carefully selected patients with refractory ARDS. Further studies are required to validate our outcome and adjust the indication for ECMO therapy in patients with severe immunosuppression. Additionally, more research is warranted to explore the clinical characteristics and predictors for ECMO success in immunocompromised patients, the timing of ART and its association with successful ECMO decannulation, and specific considerations and management of ECMO in these patients.