Open Access

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

  • Robertas Samalavicius1,
  • Mindaugas Serpytis1, 2,
  • Donata Ringaitiene1, 2,
  • Daiva Grazulyte1,
  • Ruta Bertasiute3, 4,
  • Bernardas Rimkus4,
  • Raimonda Matulionyte5, 6,
  • Ruta Ambrazaitiene7,
  • Jurate Sipylaite1, 2,
  • Tomas Kacergius8 and
  • Laimonas Griskevicius3, 4Email author
AIDS Research and Therapy201411:37

https://doi.org/10.1186/1742-6405-11-37

Received: 25 June 2014

Accepted: 8 November 2014

Published: 21 November 2014

Abstract

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.

Keywords

HIVveno-venous ECMOARDSmultidrug resistant bacteriaVAP

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 PaO2/FiO2 (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 gas-exchange 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 (FiO2 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, paO2/FiO2 of 84 mmHg on 85% of FiO2 and 16 cm H2O of PEEP. As well patient had permissive hypercapnia with CO2 of 87 mmHg; Murray score was 4 (up to four points in each of four categories; PaO2/FiO2, number of quadrants with alveolar consolidation, PEEP, and compliance) [6]; pulmonary compliance was only 4 ml/cm H2O; with pressure control ventilation of 30 cm H2O 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 paO2/FiO2 of less than 80 mmHg on 90% of FiO2 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 (http://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 H2O, his respiratory tidal volume was only 1–2 mL/kg to keep the ventilation pressure safe at <30 cm H2O. The patient had lung infiltration of 4 quadrants seen on chest x-ray (Figure 1). The white blood cell (WBC) count was 8.72 × 109/L (neutrophils 7.71 × 109/L, lymphocytes 0.66 × 109/L), platelets 257 × 109/L, hemoglobin 109 g/l, lactate 1.36 mmol/L and C-reactive protein (CRP) was 93 mg/L. On the first day at VUHSK, the patient was confirmed HIV positive (positive anti-HIV ½ Ag/Ab, Western Blot analysis showed three bands (p41, gp120 and p51) and HIV-1 RNA was 2.22 million copies/mL), his CD4 cell count was 134 cells/μL. The blood sample was positive for CMV DNA (442420 copies/mL). The bronchoalveolar lavage (BAL) fluid WBC count was 1.17 × 109/L (99% neutrophils) and was positive for CMV DNA (76740 copies/mL), Candida glabrata and MDR Acinetobacter baumanii. The diagnosis of ARDS, HIV infection, nosocomial VAP and possible CMV pneumonitis was made. Colistin, Linezolid, Imipenem, Ganciclovir and Anidulafungin were started. ART consisting of Kivexa (Abacavir and Lamivudine) and Kaletra (Lopinavir and Ritonavir) was initiated. The patient was continued with MV, full intensive care and intermittent vasopressor support. Blood flow during ECMO was tailored to achieve acceptable oxygenation. 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.
Figure 1

Chest x- ray on admission at VUHSK (3 hours after ECMO start) .

Table 1

Nosocomial infections and treatment

ICU day

Bacteria

Fungus

Virus

CRP, mg/L

Treatment

MIC, mg/L

Administration route

Daily dose

Acinetobacter baumanii*

Pseudomonas aeruginosa**

Pseudomonas fluorescens

Enterobacter aerogenes

Candida glabrata

Candida parapsilosis

Cytomegalovirus (CMV)

1

BAL/CAT

   

BAL/CAT

 

BAL/BL

93

Colistin

1

i.v.

13.5 m. IU

Ganciclovir

-

i.v.

0.8 g

3

SP

      

165

Colistin

1

i.v.

13.5 m. IU

8

    

BAL

  

77

Anidulafungin

0.125

i.v.

0.1 g

11

BAL

      

151

Colistin

1

i.v.

13.5 m. IU

16

 

BAL

     

286

Ciprofloxacin

0.5

i.v.

1.2 g

24

 

BAL/BL

     

22

Ciprofloxacin

0.5

i.v.

2.4 g

Colistin

2

i.v./inh

13.5/6 m. IU

28, 35, 39

BAL/ UR

      

149-157

Colistin

0.5-2

i.v./inh

13.5/9 m. IU

43

BAL/UR

      

162

Ampicillin Sulbactam

2

i.v.

36 g

51

 

BAL

     

98

Cefepim

4

i.v.

6 g

63

BAL

      

86

Colistin

0.5

i.v./inh

13.5/15 m. IU

65, 70

     

BL/ CAT

 

73

Amphotericin B

0.5

i.v.

0.08 g

75

  

CAT

CAT

CAT

  

90

Ciprofloxacin

0.38

i.v.

2.4 g

Cefepim

4

i.v.

6 g

Imipenem

1

i.v.

3 g

Amphotericin B

0.19

i.v.

0.08 g

77

   

CAT

   

108

Imipenem

<0.25

i.v.

3 g

ICU – intensive care unit, CRP – C-reactive protein, MIC – minimal inhibitory concentration, BL – blood, BAL – bronchoalveolar lavage, CAT – catheter, UR – urine, i.v. – intravenous, inh.–inhaled, m. – million, IU – international units.

*Acinetobacter baumanii was carbapenems (Imipenem, Meropenem MIC 32 mg/L), aminoglycosyde (Amikacin MIC 256 mg/L, Gentamycin MIC 24 mg/L) and cephalosporin (Cefepim MIC 48 mg/L) resistant;

**Pseudomonas aeruginosa was carbapenems (Meropenem MIC 32 mg/L), cephalosporin (Cefepim MIC 12 mg/L) resistant.

Table 2

Complications and their treatment during ECMO

ICU day

Complications

Treatment/Procedures

1- 59

Bilateral pneumothorax

Pleural cavity drainage

25, 31, 51

Pulmonary hemorrhage

Endobroncheal hemostasis

38

Tilt of left jugular vein cannula with blood loss of 2 liters

Cannula reinserted, transfusions of packed red blood cells and platelets

46

Blood-clot masses in pleural cavity

Open right side thoracotomy with clot removal and lung decortication

48

Left side tension pneumothorax with cardiogenic shock

Pleural cavity drainage, resuscitation

52

Bleeding from tracheostoma

Endobroncheal hemostasis

Endrobronchial clot-masses

Bronchoscopy and clot-mass removal

60

Cannula associated deep vein thrombosis

Heparin, compression therapy

Despite aggressive treatment, improvement of pulmonary mechanics was slow (tidal volume with Ppeak 30 cm H2O was only up to 2 ml/kg, compliance remained at 1–4 ml/cm H2O). 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 Ppeak 27 cmH2O and compliance 9–10 ml/cm H2O).

The first oxygenator was exchanged on day 38 after decrease in function. The patient was weaned off ECMO after 56 days. Unfortunately, 48 hours later, acute hypercapnic respiratory failure developed (pCO2 190 mmHg, pH 7.05). The veno-venous ECMO was reinstituted with successful weaning after 48 hours. MV was continued for additional 18 days. 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.
Figure 2

Chest x- ray after weaning off ECMO.

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 [79]. 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) [1214] 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 CO2 exchange recovery often trailing that of O2[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. Long-distance 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.

Abbreviations

ARDS: 

Acute respiratory distress syndrome

ART: 

Antiretroviral therapy

BAL: 

Bronchoalveolar lavage

CMV: 

Cytomegalovirus

CRP: 

C – reactive protein

CT: 

Computer tomography

DNA: 

Deoxyribonucleic acid

ECMO: 

Extracorporeal membrane oxygenation

HIV: 

Human immunodeficiency virus

ICU: 

Intensive care unit

IRIS: 

Immune reconstitution inflammatory syndrome

MDR: 

Multidrug resistant

MV: 

Mechanical ventilation

PEEP: 

Positive end-expiratory pressure

RNA: 

Ribonucleic acid

VAP: 

Ventilator associated pneumonia

VUHSK: 

Vilnius University Hospital Santariskiu Klinikos

WBC: 

White blood cell.

Declarations

Authors’ Affiliations

(1)
Center of Anaesthesiology, Intensive Care and Pain Management, Vilnius University Hospital Santariskiu Klinikos
(2)
Clinics of Anaesthesiology and Intensive Care, Faculty of Medicine, Vilnius University
(3)
Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos
(4)
Clinics of Internal, Family Medicine and Oncology, Faculty of Medicine, Vilnius University
(5)
Department of Infectious, Chest diseases, Dermatovenerology and Allergology, Faculty of Medicine, Vilnius University
(6)
Center of Infectious Diseases, Vilnius University Hospital Santariskiu Klinikos
(7)
Center of Laboratory Medicine, Vilnius University Hospital Santariskiu Klinikos
(8)
Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Faculty of Medicine, Vilnius University

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Copyright

© Samalavicius et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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