Extracorporeal membrane oxygenation in acute respiratory distress syndrome due to influenza A (H1N1)pdm09 pneumonia. A single-center experience during the 2013-2014 season

ABSTRACT

Objective:

This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy.

Methods:

This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014.

Results:

A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge.

Conclusion:

The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.

Keywords:
Extracorporeal membrane oxygenation; Respiratory distress syndrome, acute; Influenza A virus, H1N1 subtype

RESUMO

Objetivo:

Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea.

Métodos:

Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014.

Resultados:

Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar.

Conclusão:

Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves.

Descritores:
Oxigenação por membrana extracorpórea; Síndrome do desconforto respiratório do adulto; Vírus da Influenza A subtipo H1N1

INTRODUCTION

Extracorporeal membrane oxygenation (ECMO) has been a therapeutic option for severe acute respiratory distress (ARDS) for approximately forty years.⁽¹⁾ The efficacy of ECMO for treating severe ARDS in adults has been supported by a single randomized controlled trial, which demonstrated a significant improvement in survival, with good neurological function in 180 patients randomized for referral to ECMO consideration versus conventional ventilator support (CESAR trial). This study was published in the fall of 2009, just as a global pandemic of a newly emergent H1N1 influenza virus, or swine flu, peaked.

This pandemic originated in Mexico in March 2009,⁽²⁾ and it was found to have resulted from a quadruple re-assortment between 2 swine, 1 human, and 1 avian influenza strains.^(3,4) The epidemiological expression of this pandemic was distinct compared to previous typical seasonal influenza activity.⁽⁵⁾ The influenza-related hospitalization rate for adults 18 - 49 years of age increased six-fold.^(6-8) Unusually high numbers of young, previously healthy adults suffered severe ARDS requiring mechanical ventilation and, in some centers, ECMO. The Centers for Disease Control and Prevention estimated that 12,500 deaths resulted in the United States,⁽⁶⁾ including 85% younger than 65 years of age. When the relative youth of the patients who succumbed was considered, it was estimated that 334,000 - 1,973,000 years of life were lost in the pandemic.⁽⁷⁾ The predilection for severe disease in young adults was attributed to the immune naïve status of younger patients in relation to H1N1 influenza strains. Fourteen studies from Europe, Japan, the United States and Australia/New Zealand reported ECMO treatment results from a cumulative population of 487 patients with H1N1 influenza during the 2009 pandemic, with reported survival rates ranging from 32 - 92%.^(9-12)

The CESAR trial and 2009 flu pandemics were important motivators in the initiation of our ECMO program in May 2010.⁽¹³⁾ From 2010-2012, however, H3N2 emerged as the predominant clinical strain of influenza A, and the apparent need for ECMO support for influenza patients at our institution dropped sharply.⁽¹⁴⁾ H1N1 then re-emerged in the fall of 2013.⁽¹⁵⁾ Seasonal influenza A activity in the United States began to increase in mid-November 2013, and referrals of patients with severe ARDS due to influenza A quickly increased at our institution in January 2014. Other ECMO centers in Arizona simultaneously experienced peak ECMO demand. Although we coordinated our efforts, our combined capacity to provide ECMO was nearly completely engaged in February 2014.

This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy.

METHODS

The Banner Health Institutional Review Board approved this study, and informed consent and ethical approval requirements were waived (Project # 01-15-0112).

All adult patients who were treated with veno-venous ECMO (vvECMO) for severe microbiologically proven influenza A during the winter of 2013-14 in our medical/surgical intensive care unit at Banner University Medical Center were included. Influenza A virus was detected through polymerase chain reaction, direct fluorescent antigen, rapid enzyme immunoassay test, and/or viral cultures, in clinical specimens obtained through nasopharyngeal swabs, suction of endotracheal secretions or bronchoalveolar lavage. Patients were triaged to vvECMO at the discretion of intensivist and cardiothoracic surgeons. Our triage policy favors vvECMO in patients with an arterial oxygen partial pressure to fraction of inspired oxygen (PaO₂/FiO₂) ratio < 100, who do not have life-threatening co-morbidities and who have not received prolonged injurious mechanical ventilation (> 7 days) likely to have resulted in severe ventilator-associated lung injury. Venous access is typically achieved with 27 - 31 F Avalon catheters placed in the right internal jugular vein. The Seldinger technique was used to insert the catheter. Correct positioning was confirmed through fluoroscopy and chest X-ray. Maquet Rotaflow^® and Maquet Cardiohelp^® ECMO pumps and Quadrox oxygenators were used. The ECMO flow rates were set to achieve arterial oxygen saturations > 85%, while limiting negative inflow pressure to less than 100mmHg. Oxygen was used as our sweep gas and titrated to achieve adequate arterial partial pressure of carbon dioxide (PaCO₂). Non-adjusted heparin infusions at 1000 units per hour were typically administered. The ventilator settings targeted a lung-rest strategy, generally with fraction of inspired oxygen (FiO₂) ≤ 50% and peak airway pressures of 20 - 25cmH₂0.

We collected the following data: the patient demographics, risk factors for severe influenza H1N1 pneumonia and major co-morbidities, respiratory parameters before the ECMO initiation, technical characteristics of ECMO therapy, complications and outcomes. Illness severity was determined using the Sequential Organ Failure Score Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluations score (APACHE IV). Secondary pneumonias were diagnosed through clinical and radiographic findings, in conjunction with quantitative bronchoalveolar lavage cultures.

RESULTS

A total of 10 patients received vvECMO for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for ECMO consideration, all within 72 hours of initiation of mechanical ventilation. The clinical features and management, complications and outcomes details are described in table 1. The median patient age was forty years, and 30% were female. Seven patients were obese, with a body mass index greater than 30kg/m². Four patients had significant comorbidities, including chronic obstructive pulmonary disease and coronary artery disease. Most patients, however, were otherwise previously healthy, with few comorbidities. One patient was pregnant and underwent an emergency Caesarean section before starting ECMO. None of our patients had received seasonal influenza vaccinations.

Table 1
Baseline characteristics

Patient	Age	Sex	BMI	Co morbidities	Viral testing	Rescue therapy	p/f ratio	SOFA at ECMO initiation	Days on ventilator prior to ECMO
1	27	M	26.5	None	Rapid antigen	Proning	62	13	< 24 hours
2	31	M	41.6	None	Rapid antigen	Prone, Inhaled nitric oxide	44	13	< 24 hours
3	42	M	40	Hypertension, smoking	Viral culture	None	45	10	48 hours
4	44	F	52	Asthma, heart failure	Rapid antigen	Neuromuscular blocking agents, HFOV, inhaled nitric oxide, Prone	43	11	72 hours
5	30	F	NA	Pregnant	DFA	Neuromuscular blocking agents	69	13	24 hours
6	58	M	32	CLL, COPD, smoking	Viral PCR and culture	Bilevel ventilation	66	9	5 days
7	66	M	37	Hypertension, WPW	DFA	Inhaled nitric oxide	56	12	48 hours
8	34	M	33.3	None	PCR	Bilevel ventilation	57	14	24 hours
9	41	F	25.9	Asthma, ulcerative colitis	PCR	None	63	10	24 hours
10	40	M	50	None	PCR	None	49	16	24 hours

• BMI - body mass index; SOFA - Simplified Organ Function Assessment; ECMO - extracorporeal membrane oxygenation; M - male; F - female; HFOV - high frequency oscillator ventilation; NA - no assessment; DFA - direct fluorescent antigen testing; CLL - chronic myeloid leukemia; COPD - chronic obstructive pulmonary disorder; WPW - Wolf-Parkinson White; PCR - polymerase chain reaction.

Influenza virus was diagnosed in all patients using at least one of the following viral diagnostic tests: positive reverse-transcriptase polymerase chain reaction (Quest Diagnostics, nine patients), positive viral culture (Quest Diagnostics, two patients), and positive direct fluorescent antibody staining (Quest Diagnostics, three patients). Co-infection with other viruses was found in two patients, one with metapneumovirus and another with respiratory syncytial virus. Nine patients had a bronchoscopy with bronchial wash and lavage performed within 24 hours after hospitalization at our center. Respiratory cultures were sent for viral, bacterial and fungal analysis.

Most patients demonstrated typical symptoms of influenza for at least a week before medical attention was sought but then rapidly deteriorated over 48 - 72 hours. Upon admission, nine patients presented with septic shock requiring vasopressors. The median PaO₂/Fi0₂ ratio was 62.5. Six patients had severe and bilateral air space disease involving three or four quadrants. The most common radiological patterns were dense consolidation in all ten patients, ground glass opacities in two patients and pleural effusions in one patient. Interestingly, one patient had a normal chest radiograph upon admission and then, forty-eight hours after admission, progressed to having infiltrates involving four quadrants.

Half of the patients received volume-controlled ventilation, and half received airway pressure release ventilation prior to the initiation of ECMO (Table 2). Oseltamivir was started after a median 24 hours following symptom onset. Three patients received inhaled nitric oxide, and four patients were prone-positioned as rescue therapy before ECMO was initiated. Nine patients were placed on ECMO within 48 hours of admission, and one was placed on ECMO after six days of mechanical ventilation. The median SOFA score at the time of ECMO initiation was 12. Hemorrhagic complications occurred in a total of 6 patients. Four patients suffered bleeding from the ECMO catheter site, which required the temporary discontinuation of heparin. Two patients required transfusions of at least two units of packed red blood cells. Gastrointestinal bleeding was noted in two patients, and it resolved with blood transfusion and temporary withholding of heparin. Entrainment of air into ECMO circuit occurred in one case, but it did not result in systemic air embolization. Six patients suffered seven episodes of secondary bacterial ventilator-associated pneumonia: five due to Pseudomonas aeruginosa, one due to methicillin-susceptible Staphylococcus aureus and one due to Enterococcus cloacae. One patient each suffered acute cardiomyopathy and diffuse alveolar hemorrhage presumably related to influenza. One patient who had underlying lymphoproliferative malignancy developed hemophagocytic lymphohistiocytosis shortly before his death. No patient suffered barotrauma.

Table 2
Additional ventilator settings

Patient	Mechanical ventilator settings before ECMO	Mechanical ventilator settings after ECMO	Maximum first day ECMO sweep (L/Min)	Maximum first day ECMO flow (L/min)	Addition of steroids Yes/No	Additional rescue therapies during ECMO
1	APRV, 100 FiO2, Th/Tl, 4/0.5s	CMV, TV-500, PEEP-5,50%	2	5	No	None
2	CMV, TV-350, PEEP-16, FiO2-80	CMV-350, PEEP-14,50%	6	4.1	No	None
3	CMV, TV- 450, PEEP-20, FiO2-80	PS -15, FiO2-40	7	4.0	Yes	None
4	HFOV, 100%, Mean pr-35	CMV, TV-200, PEEP-20, FiO2-50%	6	4.5	Yes	Proning, inhaled nitric oxide
5	APRV, Th/Tl-3.7/0.3, FiO2-100	TV-250, PEEP-20, FiO2-50	5	2.7	No	None
6	CMV, TV-350, PEEP-20, FiO2-100	APRV, Pr-22/15, Th/Tl-4/0.8, FiO2-100	2	4	Yes	None
7	CMV-400, PEEP-20, FiO2-100	CMV, TV-350, PEEP-14, FiO2-45	4.5	3.3	No	None
8	APRV, Th/Tl-/0.5, FiO2-60	APRV-26/16, Th/tl 4/0.5,50%	4.5	3.7	No	None
9	CMV 350, PEEP-15, Fi02-100	CMV, TV-300, PEEP-10, FiO2-30	2	3.7	No	None
10	CMV, TV 350, PEEP-20, FiO2-100	CMV, TV-350, PEEP-15, FiO2-40	7	3.5	No	None

• ECMO - extracorporeal membrane oxygenation; APRV - airway pressure release ventilation; FiO₂ - fraction of inspired oxygen; Th/Tl- time high/time low; CMV - controlled mandatory ventilation; TV - tidal volume; PEEP - positive end expiratory pressure, PS - pressure support; HFOV - high-frequency oscillator ventilation.

The median duration of mechanical ventilation was 22 days (range, 14 - 32), and vvECMO was provided for a median of 12.5 days (range, 8 - 19 days). The median length of stay in the intensive care unit was 27 days (range, 14 - 39), and the median hospital length of stay was 29 days (range, 16 - 46). In two cases, ECMO was terminally withdrawn after the patients failed to recover and after discussions with the surrogate decision makers. Among our eight survivors, all were ambulatory, and seven were on room air at the time of discharge to home.

DISCUSSION

Here, we describe the outcomes of a cohort of ten patients with severe H1N1 ARDS treated with vvECMO during the winter of 2013-2014 at our institution. The statewide need for ECMO support increased sharply this season compared to prior years, in conjunction with the re-emergence of H1N1 influenza. The observed increase in ECMO utilization was not reflected in the overall mortality of influenza during the 2012-2013 winter, which was not significantly increased compared to the 2010-2012 seasons.⁽¹⁶⁾ It appears that a relatively small subset of young adults who developed severe complications related to H1N1 influenza impacted the ECMO utilization profoundly, without significantly contributing to the much larger overall mortality rate. This phenomenon was also observed in the 2009 pandemic.^(17,18)

In many aspects, our patients were similar to those reported to have received ECMO for H1N1 influenza in 2009. The median patient age of 40 in our series is similar to that previously reported.^(18-20) Other characteristics, such as obesity and comorbidities, were similar to those reported in previous studies.^(9,18,21) The SOFA scores of our patients were higher than those reported in a few recently published studies,^(11,18) however, the PaO₂/FiO₂ ratio and lung injury score were similar to those in other reported studies.^(10,17,18) ECMO was started within 48 hours of mechanical ventilation in nine patients, similar to other studies.^{(11,17,18,21)}

Life-threatening complications were common in our cohort (Table 3). The most frequent complication seen in patients treated with ECMO was bleeding.^(22-27) Cannula insertion sites, which were the most frequent bleeding site reported in the Extracorporeal Life Support Organization (ELSO) registry (occurring in 17% of patients), were also the most frequent bleeding site in our study.⁽²⁶⁾ Nine patients suffered septic shock, and six required continuous renal replacement therapy. Our patients suffered a high rate of ventilator-associated pneumonia (VAP), despite active quality improvement efforts at our hospital to prevent VAP. The incidences of secondary bacterial VAP have ranged from 40 to 71% in previous studies of influenza patients on ECMO,^(9,12,23) and we are not the first group to report a preponderance of gram-negative pathogens.^(9,28) It is likely that post-influenza bacterial pneumonias are fundamentally different than VAP in non-influenza patients and more difficult to prevent. Less common complications, such as diffuse alveolar hemorrhage, myocarditis and hemophagocytic lymphohistiocytosis, significantly impacted morbidity and mortality rates in our patients. Virus-associated hemophagocytic syndrome has been reported to be a major cause of death in 9 of 17 patients who received ECMO for H1N1 Influenza related ARDS.⁽²⁹⁾ Renal dysfunction is also a common complication, with six patients requiring continuous renal replacement therapy, and it reportedly occurred in 13% of patients in the ELSO registry.⁽²⁶⁾ In an analysis of 72 patients receiving ECMO for respiratory failure, only pre-ECMO serum creatinine levels correlated with survival.⁽³⁰⁾ It is unclear if this finding is related to the overall severity of organ dysfunction and not specifically to ECMO.

Table 3
Complications

Complications	N
Septic shock requiring vasopressors	9
Acute renal failure requiring continuous renal replacement therapy	6
Viral cardiomyopathy	1
Diffuse alveolar hemorrhage	1
Ventilator associated pneumonia	6
Hemophagocytic lymphohistiocytosis	1

Despite the complications described above, our outcomes were encouraging and comparable to those reported during the 2009 H1N1 pandemic (Table 4). Our 80% survival rate is similar to that reported by Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators (79%), Zangrillo et al. (72%), Pham et al. (64%) and Holzgraefe et al. (92%).^(9,11,18,21) A small study in a French hospital (n = 12) reported a high survival rate, despite many complications, such as VAP, which was observed in 6/12 patients, and major hemorrhage, which was reported in 8/12 patients.⁽²⁵⁾ Our surviving patients were all discharged with good functional status. Other small observational studies have reported lower survival rates, including a 35% survival rate reported in a Japanese series (n = 14), 39% survival in a series from Germany (n =18), 44.4% in some French centers (n = 9) and a 44.4% survival rate reported by Spanish hospitals (n = 9).^{(19,22,24,27)} While these findings could be attributed to hemorrhagic complications and longer durations to the initiation of ECMO, lack of experience and technical challenges could also have influenced survival rates.^(19,22,24) Although ECMO is an expensive support modality, its cost effectiveness is enhanced in the treatment of relatively young patients likely to enjoy good functional status at discharge. Such patients are likely to enjoy many future years of high-quality life.

Table 4
Outcomes

Outcomes	N
Median duration of days on ECMO	12.5 (8 - 19)
Median duration of days on mechanical ventilation	22 (14 - 32)
Median duration of days in the intensive care unit	27.5 (14 - 39)
Survivors	8 (80%)

• ECMO - extracorporeal membrane oxygenation.

Regional ECMO triage was an important factor related to our patient series. It was our shared statewide experience that influenza A caused many more cases of severe ARDS requiring vvECMO in 2013-2014 compared to any previous recent year, with the possible exception of 2009. To the best of our knowledge, this result was a legitimate reflection of the virulence of the strain and not due to triage bias. By January 2014, our ECMO utilization was the highest that we had experienced in the short history of our program. At several points over the winter, all four of our available ECMO units were in use, necessitating the loan of a backup circuit. A statewide organization of ECMO providers was formed to discuss management and provide a state-wide triage system in which patients could be transferred from one ECMO center to another (if needed), depending on the availability of ECMO circuits/pumps. This system was effective in placing all patients for whom ECMO was indicated in a center (located somewhere in the state) that could provide the required care. We believe that this cooperation was instrumental in the high survival rate reported here.

CONCLUSION

H1N1 might re-emerge in the future and cause severe respiratory disease, despite the increasing immunity of our population. Other respiratory viruses, such as H5N1 avian influenza and Middle Eastern respiratory virus MERS, may also emerge to burden regional extracorporeal membrane oxygenation capacities with unpredictable timing. We believe that extracorporeal membrane oxygenation capacity should be regionally planned and that triage should be regionally coordinated. Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.

• Responsible editor: Luciano César Pontes de Azevedo
• Key messages
  – H1N1 might re-emerge in the future and cause severe respiratory disease.– In our experience, HIN1 primarily affected young adults who developed severe complications.– Our mortality rate was encouraging despite the number of complications.– Even a new ECMO program can play an important role in patient care and provide excellent outcomes.– ECMO capacity should be regionally planned, and triage should be regionally coordinated.
  

  – H1N1 might re-emerge in the future and cause severe respiratory disease. – In our experience, HIN1 primarily affected young adults who developed severe complications. – Our mortality rate was encouraging despite the number of complications. – Even a new ECMO program can play an important role in patient care and provide excellent outcomes. – ECMO capacity should be regionally planned, and triage should be regionally coordinated.

ACKNOWLEDGMENTS

We thank Rebecca Sunenshine, MD (CDR, US Public Health Service, CDC Career Epidemiology Field Officer and Medical Director, Disease Control Division, Maricopa County Department of Public Health, Phoenix, Arizona, USA) and Vjollca Berisha, MD, MPH (Senior Epidemiologist, Maricopa County Department of Public Health, Phoenix, Arizona, USA) for their technical assistance in providing us with the adult influenza mortality rates in Maricopa County by age group from the 2009-2010 to 2013-2014 seasons.

We also thank the following physicians who participated in the care of patients who were included in this case series: Thomas Bajo, MD, Gregory Chu, MD, Leonor Echevarria, MD, Kenith Fang, MD, Roxanne Garcia-Orr, MD, and, Edwin Yu, MD.

REFERÊNCIAS

• ¹
  Hill JD, O'Brien TG, Murray JJ, Dontigny L, Bramson ML, Osborn JJ, et al. Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Engl J Med. 1972;286(12):629-34.
• ²
  Centers for Disease Control and Prevention (CDC). Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep. 2009;58(17):467-70.
• ³
  Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team; Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360(25):2605-15. Erratum in: N Engl J Med. 2009;361(1):102.
• ⁴
  Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325(5937):197-201.
• ⁵
  Jhung MA, Swerdlow D, Olsen SJ, Jernigan D, Biggerstaff M, Kamimoto L, et al. Epidemiology of 2009 pandemic influenza A (H1N1) in the United States. Clin Infect Dis. 2011;52 Suppl 1:S13-26.
• ⁶
  Shrestha SS, Swerdlow DL, Borse RH, Prabhu VS, Finelli L, Atkins CY, et al. Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010). Clin Infect Dis. 2011;52 Suppl 1:S75-82.
• ⁷
  Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary estimates of mortality and years of life lost associated with the 2009 A/H1N1 pandemic in the US and comparison with past influenza seasons. PLoS Curr. 2010;2:RRN1153.
• ⁸
  Cox CM, D'Mello T, Perez A, Reingold A, Gershman K, Yousey-Hindes K, Arnold KE, Farley MM, Ryan P, Lynfield R, Morin C, Baumbach J, Hancock EB, Zansky S, Bennett NM, Thomas A, Schaffner W, Finelli L; Emerging Infections Programs Network. Increase in rates of hospitalization due to laboratory-confirmed influenza among children and adults during the 2009-10 influenza pandemic. J Infect Dis. 2012;206(9):1350-8.
• ⁹
  Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators, Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, et al. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA. 2009;302(17):1888-95.
• ¹⁰
  Töpfer L, Menk M, Weber-Carstens S, Spies C, Wernecke KD, Uhrig A, et al. Influenza A (H1N1) vs non-H1N1 ARDS: analysis of clinical course. J Crit Care. 2014;29(3):340-6.
• ¹¹
  Zangrillo A, Biondi-Zoccai G, Landoni G, Frati G, Patroniti N, Pesenti A, et al. Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care. 2013;17(1):R30.
• ¹²
  Patroniti N, Zangrillo A, Pappalardo F, Peris A, Cianchi G, Braschi A, et al. The Italian ECMO network experience during the 2009 influenza A (H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med. 2011;37(9):1447-57.
• ¹³
  Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. CESAR trialcollaboration. Lancet. 2009;374(9698):1351-63. Erratum in Lancet. 2009;374(9698):1330.
• ¹⁴
  Lindstrom S, Garten R, Balish A, Shu B, Emery S, Berman L, et al. Human infections with novel reassortant influenza A(H3N2)v viruses, United States, 2011. Emerg Infect Dis. 2012;18(5):834-7.
• ¹⁵
  Centers for Disease Control and Prevention (CDC). Update: influenza activity - United States, September 29-December 7, 2013. MMWR Morb Mortal Wkly Rep. 2013;62(50):1032-6.
• ¹⁶
  Centers for Disease Control and Prevention (CDC). Update: Influenza activity - United States, October 2, 2011-February 11, 2012. MMWR Morb Mortal Wkly Rep. 2012;61(7):123-8.
• ¹⁷
  Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA. 2011;306(15):1659-68.
• ¹⁸
  Pham T, Combes A, Rozé H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, Clavel M, Constan A, Marie Richard JC, Brun-Buisson C, Brochard L; REVA Research Network. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2013;187(3):276-85.
• ¹⁹
  Papadopoulos N, Ahmad Ael-S, Marinos S, Moritz A, Zierer A. Extracorporeal membrane oxygenation for influenza-associated acute respiratory distress syndrome. Thorac Cardiovasc Surg. 2013;61(6):516-21.
• ²⁰
  Cianchi G, Bonizzoli M, Pasquini A, Bonacchi M, Zagli G, Ciapetti M, et al. Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center. BMC Pulm Med. 2011;11:2.
• ²¹
  Holzgraefe B, Broomé M, Kalzén H, Konrad D, Palmér K, Frenckner B. Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure. Minerva Anestesiol. 2010;76(12):1043-51.
• ²²
  Takeda S, Kotani T, Nakagawa S, Ichiba S, Aokage T, Ochiai R, Taenaka N, Kawamae K, Nishimura M, Ujike Y, Tajimi K; Committee of Crisis Control, the Japanese Society of Respiratory Care Medicine and Committee of Pandemic H1N1 Surveillance, the Japanese Society of Intensive Care Medicine. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) severe respiratory failure in Japan. J Anesth. 2012;26(5):650-7.
• ²³
  Roncon-Albuquerque R Jr, Basílio C, Figueiredo P, Silva S, Mergulhão P, Alves C, et al. Portable miniaturized extracorporeal membrane oxygenation systems for H1N1-related severe acute respiratory distress syndrome: a case series. J Crit Care. 2012;27(5):454-63.
• ²⁴
  Bonastre J, Suberviola B, Pozo JC, Guerrero JE, Torres A, Rodríguez A, Martín-Loeches I; SEMICYUC-CIBERES-REIPI working group. [Extracorporeal lung support in patients with severe respiratory failure secondary to the 2010-2011 winter seasonal outbreak of influenza A (H1N1) in Spain]. Med Intensiva. 2012;36(3):193-9. Spanish.
• ²⁵
  Beurtheret S, Mastroianni C, Pozzi M, D'Alessandro C, Luyt CE, Combes A, et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome: single-centre experience with 1-year follow-up. Eur J Cardiothorac Surg. 2012;41(3):691-5.
• ²⁶
  Extracorporeal Life Support Organization. Registry report: international summary. Ann Arbor: ELSO; July 2012.
• ²⁷
  Roch A, Lepaul-Ercole R, Grisoli D, Besserau J, Brissy O, Castanier M, et al. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study. Intensive Care Med. 2010;36(11):1899-905.
• ²⁸
  De Rosa FG, Corcione S, Pagani N, Stella ML, Urbino R, Di Perri G, et al. High rate of respiratory MDR gram-negative bacteria in H1N1-ARDS treated with ECMO. Intensive Care Med. 2013;39(10):1880-1.
• ²⁹
  Beutel G, Wiesner O, Eder M, Hafer C, Schneider AS, Kielstein JT, et al. Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection. Crit Care. 2011;15(2):R80.
• ³⁰
  Wagner K, Risnes I, Abdelnoor M, Karlsen HM, Svennevig JL. Is it possible to predict outcome in pulmonary ECMO? Analysis of pre-operative risk factors. Perfusion. 2008;23(2):95-9.

Publication Dates

• Publication in this collection
  28 Sept 2017
• Date of issue
  Jul-Sep 2017

History

• Received
  20 Nov 2016
• Accepted
  15 Jan 2017