Successful use of extracorporeal membrane oxygenation in a human immunodeficiency virus infected patient with severe acute respiratory distress syndrome

Introduction We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory distress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria that was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO). Case report A 25 year old male with no significant past medical history had been admitted to a local hospital due to dyspnea and fever. His pulmonary function subsequently failed necessitating mechanical ventilation (MV) and introduction of ECMO support. The patient was transported for 300 km by road on ECMO to a tertiary medical center. The diagnosis of ARDS, HIV infection and MDR bacterial and fungal VAP was made. Patient was successfully treated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with complete resolution of the respiratory symptoms. Conclusion HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART could be successfully managed with ECMO.


Background
According to Berlin definition [1] acute respiratory distress syndrome (ARDS) is characterized by 1) lung injury of acute onset, within 1 week of an apparent clinical insult and with progression of respiratory symptoms; 2) bilateral opacities on chest imaging not explained by other pulmonary pathology (e.g. pleural effusion, pneumothorax, or nodules); 3) respiratory failure not explained by heart failure or volume overload; 4) mechanical ventilation with decreased PaO 2 /FiO 2 (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen).
Extracorporeal membrane oxygenation (ECMO) is salvage therapy for selected group of patients with gasexchange failure refractory to mechanical ventilation (MV). Severe hypoxemia despite the application of high levels of PEEP or uncompensated hypercapnia are the main indications for ECMO treatment. Mechanical ventilation at high settings (FiO 2 90%, Pplat >30 mmHg) for more than 7 days, immunosupression and intracranial hemorrhage are the main contraindications for using this mode of treatment. ECMO is associated with considerable risks for the patient, including but not limited to bleeding, infection or mechanical failure of the ECMO circuit [2]. Recently, ECMO has been shown to be very effective in treating ARDS patients during H1N1 pandemic [3] and successful use of ECMO in immunocompromised patients has been reported [4,5].
However, it remains a relative contraindication to extracorporeal life support.
The purpose of this report is to describe an human immunodeficiency virus (HIV) infected patient with ARDS complicated by multidrug resistant (MDR) bacterial and fungal ventilator associated pneumonia (VAP) who was successfully managed with veno-venous ECMO and off-label doses of antimicrobial agents.

Case presentation
A 25 year old male with no significant past medical history was admitted to a local hospital due to dyspnea and fever of 39°C. The patient's pulmonary computer tomography (CT) scan was consistent with alveolitis. Sputum and blood cultures were negative. Patient received empirical Amoxicillin prior to hospitalisation and Cefuroxime in hospital without any improvement. For suspected allergic alveolitis prednisolone 40 mg daily for 8 days was administered. As a result of worsening of respiratory function on day 10 of initial hospitalization, the patient was transferred to intensive care unit (ICU). 1 gram of methylprednisolone once, followed by three consecutive doses of 120 mg/per day were administered. Pulmonary function deteriorated and mechanical ventilation was initiated on day 6 in intensive care unit stay. No signs of any other organ system dysfunction were evident. Antibiotic therapy was changed to Imipenem and Vancomycine. On day 11 of MV, the patient's respiratory function deteriorated substantially. The decision was made to transfer the patient to Vilnius University Hospital Santariskiu Klinikos (VUHSK) with facilities for ECMO treatment.
When transport team arrived, tidal volume was decreasing to critical levels trying to achieve safe ventilation pressures, the patient had drained pneumothorax, paO 2 /FiO 2 of 84 mmHg on 85% of FiO 2 and 16 cm H 2 O of PEEP. As well patient had permissive hypercapnia with CO 2 of 87 mmHg; Murray score was 4 (up to four points in each of four categories; PaO 2 /FiO 2 , number of quadrants with alveolar consolidation, PEEP, and compliance) [6]; pulmonary compliance was only 4 ml/cm H 2 O; with pressure control ventilation of 30 cm H 2 O the inspired tidal volume was only 2 ml/kg. The decision was made to place the patient on veno-venous ECMO before the transfer because paO 2 /FiO 2 of less than 80 mmHg on 90% of FiO 2 and Murray score of 3-4 identifies the risk of mortality of 80% with conventional treatment and is an indication for initiation of extracorporeal life support according to the extracorporeal life support organization guidelines (www.elso.med.umich. edu/Guidelines.html). 23 French drainage cannula (Bio-Medicus, Medtronic Inc., Minneapolis, USA) was inserted percutaneously into inferior vena cava via femoral approach and 19 French return cannula was inserted into the left internal jugular vein. ECMO circuit consisted of bioline coated Quadrox PLS oxygenator and Rotaflow centrifugal pump (Maquet Cardiopulmonary AG, Rastatt, Germany). The patient was uneventfully transported for 300 km (200 minutes) by road ambulance to VUHSK, ECMO flow was 6 l/min.
On admission to VUHSK, the patient's lung compliance was 3-4 ml/cm H 2 O, his respiratory tidal volume was only 1-2 mL/kg to keep the ventilation pressure safe at <30 cm H 2 O. The patient had lung infiltration of   Ventilator settings were reduced to protective ventilation mode. During the ICU stay, aggressive treatment of numerous nosocomial infections was required (Table 1).
Complications during ECMO are detailed in Table 2.
Despite aggressive treatment, improvement of pulmonary mechanics was slow (tidal volume with P peak 30 cm H 2 O was only up to 2 ml/kg, compliance remained at 1-4 ml/cm H 2 O). For the downregulation of immune reconstitution inflammatory syndrome, intravenous methylprednisolone 1 mg/kg/dose per day for 7 days was administered on ECMO day 18 and then gradually tapered off over 15 days. This resulted in improved lung function (tidal volume increased to 4.4 mL/kg with P peak 27 cmH 2 O and compliance 9-10 ml/cm H 2 O).
The first oxygenator was exchanged on day 38 after decrease in function. The patient was weaned off ECMO After 70 days of ART, the patient's CD4 cell count increased to 268 cells/μL and the HIV-1 viral load became 591 copies/mL, lung chest X-ray is shown in Figure 2. The patient was transferred to a general ward and later discharged from hospital to continue rehabilitation. At the last clinic visit 115 days after having been discharged from ICU, the patient reported good health, had no pulmonary symptoms, could walk unassisted for more than 2 kilometers.
In total, 51 packed red blood cells and 14 platelet units were transfused. The total duration of ECMO was 58 days. The total MV duration was 87 days (11 pre ECMO, 58 ECMO and 18 post ECMO). The total VUHSK ICU stay was 84 days.

Discussion
ECMO use in immunocompromised patients is controversial because of high mortality [7][8][9]. To the best of our knowledge, there is only one report of ECMO use in HIV infected patient [5]. We had not been aware of the patient's HIV infection and thus were not biased when deciding to initiate ECMO support. Also, our patient may have had an early stage of HIV infection as witnessed by a high HIV-1 viral load in parallel with a weak antibody band spectrum on Western Blot analysis and relatively rapid CD4 count recovery. Importantly, our patient had a predominant pulmonary failure while the function of other organs was relatively preserved making veno-venous ECMO a good choice of gas-exchange support while anti-infective therapy took effect. Also, we chose an aggressive preemptive approach to diagnose and treat nosocomial superinfections. Increased cardiac output, leaky capillaries, enlarged volume of distribution and impaired tissue penetration in septic patients may lead to an inadequate concentration of antimicrobial agent at the target site [10]. Also, due to sequestration and increased volume of distribution patients on ECMO are at risk of suboptimal antimicrobial therapy [11]. Therefore, there is a tendency to use higher doses of antimicrobial agents in critically ill patients. In our case, antibiotics were changed as soon as nosocomial bacteria were identified at doses that in many cases were considerably higher (Table 1) [12][13][14] than indicated in the drug label. We did not observe unacceptable antibiotic related toxicity.
ART was initiated as soon as HIV positivity was confirmed. Of note, ART suppresses HIV replication and may cause immune reconstitution inflammatory syndrome [15]. We administered a short course of methylprednisolone resulting in improved lung function. A recent meta-analysis showed a possibility of reduced mortality and increased ventilator free days with steroids in ARDS [16].
Common complications during ECMO are pneumonia, sepsis and bleeding especially associated with invasive procedures [17]. In our case, pulmonary hemorrhage, bleeding from the cannulation site and pneumothorax (including one case of tension pneumothorax) were observed necessitating surgical and medical intervention ( Table 2). After first weaning off ECMO we observed hypercapnic respiratory failure leading to hemodynamic instability. This emphasizes uneven pulmonary gas exchange reconstitution with CO 2 exchange recovery often trailing that of O 2 [18].

Conclusions
In individual cases, ECMO could be succesfully applied in HIV infected patients with ARDS refractory to conventional treatment and ventilator-associated pneumonia caused by multidrug resistant bacteria whose HIV replication is controlled by antiretroviral therapy. Longdistance transportation on ECMO may be attempted in selected cases.

Consent
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.