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Extracorporeal membrane oxygenation for cardiorespiratory failure in four patients with pandemic H1N1 2009 influenza virus and secondary bacterial infection

2010; Elsevier BV; Volume: 104; Issue: 3 Linguagem: Inglês

10.1093/bja/aep396

1471-6771

Erin M. Buckley, David Sidebotham, Alastair McGeorge, Sophia Roberts, Sara Jane Allen, John Beca,

Cardiac Structural Anomalies and Repair

We report four patients with pandemic H1N1 2009 influenza virus and secondary bacterial infection who were treated with extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure. Three of the four patients had profound shock, necessitating support with venoarterial ECMO. Two patients died during ECMO support. The two survivors had prolonged hospital stays, which were complicated by renal failure and limb ischaemia. We report four patients with pandemic H1N1 2009 influenza virus and secondary bacterial infection who were treated with extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure. Three of the four patients had profound shock, necessitating support with venoarterial ECMO. Two patients died during ECMO support. The two survivors had prolonged hospital stays, which were complicated by renal failure and limb ischaemia. Four patients with severe cardiorespiratory failure associated with pandemic H1N1 2009 influenza virus and secondary bacterial infection—three with Streptococcus pneumoniae and one with Staphylococcus aureus—were admitted to different New Zealand hospitals in July 2009. Three adult patients were referred for extracorporeal membrane oxygenation (ECMO) to the Cardiovascular Intensive Care Unit (CVICU), Auckland City Hospital, Auckland, New Zealand, and one child was referred for ECMO to the Paediatric Intensive Care Unit (PICU), Starship Children's Hospital, Auckland, New Zealand. CVICU and PICU provide a national ECMO service for New Zealand, which includes ECMO retrieval. Patient characteristics, treatments, and outcomes are listed in Table 1. All patients presented to hospital with a 24 h history of shortness of breath, preceded by several days of an influenza-like illness. At presentation, all patients had respiratory failure requiring urgent intubation and mechanical ventilation. Bilateral patchy infiltrates were present on the initial chest radiograph in all cases. Cardiovascular and renal dysfunction was present in all patients. Patients 1, 3, and 4 had markedly impaired peripheral perfusion, with cold, mottled limbs.Table 1Patient characteristics. ECMO, extracorporeal membrane oxygenation; bpm, breaths per minute; VV, venovenous; VA, venoarterial; AKA, above-knee amputationPatient1234Characteristic data Age (yr)31162713 GenderFemaleMaleMaleFemale BMI40.622.923.922.2 Co-morbiditiesNoAsthmaAsthmaNo Duration of influenza symptoms before presentation (days)75145 Secondary bacterial infectionS. pneumoniaS. pneumoniaS. pneumoniaS. aureus Acute renal failureYesYesYesYesVital signs and blood tests at presentation Peripheral arterial oxygen saturation (%)92908880 Ventilatory frequency (bpm)32504052 Heart rate (beats min−1)125150130152 Mean arterial pressure (mm Hg)75648874 White blood cell count (×109 litre−1)1.494.70.30.8 Lymphocyte count (×109 litre−1)0.880.600.20.1 Platelet count (×109 litre−1)578410492 Creatinine (µmol litre−1)202180241244Cardiorespiratory parameters and arterial blood gases before institution of ECMO Ventilatory frequency (bpm)20171925 Fractional inspired oxygen1.01.01.01.0 Peak inflation pressure (cm H2O)35394040 Positive end-expiratory pressure (cm H2O)15211717 Arterial oxygen tension (kPa)7.412.55.87.3 Arterial carbon dioxide tension (kPa)9.4>3110.18.6 Bicarbonate (mmol litre−1)15.635.615.418.8 pH6.976.736.987.09 Lactate(mmol litre−1)N/A1.65.84.0 Severe haemodynamic instability presentYesNoYesYes Poor peripheral perfusion presentYesNoYesYesECMO data Time from presentation to institution of ECMO (days)1511 Type(s) of ECMOVAVVVV, VAVA Use of distal perfusion cannulaYesNoYesNo ECMO duration (days)132457Outcome SurvivedYesNoNoYes Major morbidityIschaemic toes, renal failureRight AKA, left foot ischaemia, renal failure Open table in a new tab Pandemic H1N1 influenza virus was confirmed by the reverse transcriptase–polymerase chain reaction assay of respiratory secretions in all patients. Streptococcus pneumoniae was cultured from blood in Patients 2 and 3. Staphylococcus aureus was cultured from sputum and pleural fluid in Patient 4. In Patient 1, bacterial cultures were negative but the urinary antigen test for S. pneumoniae was positive. Patients were treated empirically with oseltamivir and broad-spectrum antibacterial drugs, which were subsequently rationalized to oseltamivir plus benzyl-penicillin (Patients 1–3) or oseltamivir plus flucloxacillin (Patient 4). Within 24 h of hospital admission, all patients had severely impaired gas exchange, despite maximal ventilatory support. Patients 1, 3, and 4 had severe shock (requiring inotropes and vasopressors at high dose), metabolic acidosis, and very poor limb perfusion. Patient 2 required only modest inotropic support. Continuous venovenous (VV) haemofiltration was used in all patients for treating anuric renal failure and metabolic acidosis. Patients 1, 3, and 4 were referred for ECMO within 24 h of hospital admission. Patient 2 was managed with conventional ventilatory support and prone positioning for 5 days before referral for ECMO. In all cases, ECMO was instituted in the referring hospital and the patients transported to CVICU (Patients 1–3) or PICU (Patient 4) on ECMO. Venoarterial (VA) ECMO was used as the primary form of extracorporeal support in Patients 1 and 4. Patient 3 was initially managed with VV ECMO, but converted to VA ECMO on day 3 due to worsening metabolic and haemodynamic status. Patient 2 was managed entirely with VV ECMO. After institution of ECMO, ventilator settings were reduced to 'rest' levels (ventilatory frequency <10 breaths per minute (bpm), peak inspiratory pressure <25 cm H2O, and fractional inspired oxygen 35. Overall mortality was 14.3%. During the same time period, 68 patients with influenza-associated acute respiratory distress syndrome received ECMO support in Australia and New Zealand, of whom 48 (71%) survived to ICU discharge.2Davies A Jones D Bailey M et al.Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome.J Am Med Assoc. 2009; 302: 1888-1895Crossref PubMed Scopus (1293) Google Scholar Median duration of ECMO support was 10 (IQR, 7–15) days. Nineteen patients (28%) had a secondary microorganism identified at the time of hospital admission, the most common being S. pneumoniae (10 patients) and S. aureus (four patients). The outcome of patients with secondary bacterial infection was not reported. Compared with other patients treated with ECMO for pandemic H1N1 influenza virus, the four patients reported here represent the extreme end of illness severity. All patients had haemodynamic instability at presentation and three rapidly developed profound shock, necessitating the use of VA ECMO. VA ECMO was used as the initial mode of support in only 7% (five of 68) of the patients treated with ECMO during the 2009 Australia and New Zealand H1N1 2009 winter pandemic.2Davies A Jones D Bailey M et al.Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome.J Am Med Assoc. 2009; 302: 1888-1895Crossref PubMed Scopus (1293) Google Scholar Poor peripheral perfusion was a striking feature in three of the four patients reported here. In the two survivors, failure to utilize, or delayed utilization of, a distal arterial perfusion cannula during VA ECMO support greatly exacerbated limb ischaemia. Additionally, both survivors had protracted and complicated hospital courses, with prolonged requirements for mechanical ventilation and renal replacement therapy. ECMO is an established therapy for treating severe respiratory failure, and its use is associated with improved survival compared with conventional treatment in patients with severe respiratory failure and high predicted mortality.3Peek GJ Mugford M Tiruvoipati R et al.Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.Lancet. 2009; 374: 1351-1363Abstract Full Text Full Text PDF PubMed Scopus (2365) Google Scholar VV ECMO is the preferred method of extracorporeal support for pneumonia and can successfully support the majority of patients with isolated respiratory failure.3Peek GJ Mugford M Tiruvoipati R et al.Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial.Lancet. 2009; 374: 1351-1363Abstract Full Text Full Text PDF PubMed Scopus (2365) Google Scholar However, VA ECMO may be required in patients with concomitant severe shock. The role of ECMO in treating patients with septic shock complicating respiratory failure is less well established than its role in treating isolated respiratory failure. However, reasonable outcomes have been demonstrated in small case series.4Lamarche Y Cheung A Walley KR Dodek P Combined use of extracorporeal membrane oxygenation and activated protein C for severe acute respiratory distress syndrome and septic shock.J Thorac Cardiovasc Surg. 2009; 138: 246-247Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 5MacLaren G Pellegrino V Butt W Preovolos A Salamonsen R Successful use of ECMO in adults with life-threatening infections.Anaesth Intensive Care. 2004; 32: 707-710Crossref PubMed Google Scholar, 6Maclaren G Butt W Best D Donath S Taylor A Extracorporeal membrane oxygenation for refractory septic shock in children: one institution's experience.Pediatr Crit Care Med. 2007; 8: 447-451Crossref PubMed Scopus (145) Google Scholar For treating concomitant septic shock, VA ECMO with high blood flow rates may be required.7MacLaren G Butt W Best D Pediatric septic shock guidelines and extracorporeal membrane oxygenation management.Crit Care Med. 2009; 37: 2143-2144Crossref PubMed Scopus (3) Google Scholar This report highlights several important issues. First, the combination of H1N1 influenza virus infection and secondary bacterial infection can result in severe cardiorespiratory failure with multi-organ involvement. Second, as secondary bacterial infection is common in critically ill patients with pandemic H1N1, it is vital that such patients are treated empirically with antimicrobial therapy targeting community-acquired Gram-positive bacteria, particularly S. pneumoniae and S. aureus, until the results of microbiological testing are available. Third, if severe respiratory failure is complicated by profound shock, VA ECMO should be considered as a viable treatment option. Finally, if VA EMCO is utilized, placement of a distal femoral artery perfusion cannula is essential to mitigate the risk of lower limb ischaemia, particularly in patients with impaired peripheral perfusion.