First case of adult ECMO was reported in 1971 with motor bike accident. But later on, in 1979 NIH trial was published which didn't show any benefit of ECMO in adult respiratory failure.  However, there were lots of fallacies in NIH study like all patients were treated with VA ECMO instead of VV ECMO, No Rest lung strategy practised; Over Heparinization & ECMO was initiated after 9 days of mechanical ventilation in all patients.  So from that time till 2009 only few cases of ECMO in adult respiratory failure are reported however it was continued to be used in neonates & paediatrics (both in cardiac & respiratory failure). In 2009, the real boost to ECMO in adult respiratory failure came mainly due to positive Cesar trial  & an outbreak of H1N1 infection across the Globe. There are ample of papers published on H1N1 & ECMO thereafter with positive outcome from various parts of the world. Now ECMO remains a well-established modality for refractory acute respiratory failure especially secondary to H1N1 infection.
In India & in many of the Asian & African countries, the incidence of acute respiratory failure secondary to other tropical infection like Malaria, dengue, leptospirosis, bacterial & viral pneumonia are much higher than H1N1 infection. ECMO is still underutilized modalities for these tropical infections mainly due to the financial reason but also because of lack of awareness & lack of published data.
Lung injury in ARDS in the tropical regions occurs due to the tropical infections, poisoning and inhalational injuries. The aetiology of ARDS can be expected to be different in India due to the higher incidence of tropical infectious diseases. [4,5] Malarial parasite, typhus-related diseases, tuberculosis, and dengue fever are some of the most important cause for ARDS in tropical countries.  The study on the global malaria mortality between 1980 and 2010 by Murray et al. published in The Lancet in Feb 2012, estimated the malaria mortality in India in 2010 at 46,800.  In 2016, an estimated 216 million cases of malaria occurred worldwide with an estimated 445 000 deaths from malaria globally, compared to 446000 estimated deaths in 2015.  The story is not far different with other tropical diseases like Dengue, Leptospirosis, Scub typhus, etc. Infections originated in one part of the world can easily spread to the rest of the world if there is any break in the chain of screening the affected in the incubation period .
ECMO program started in our centre from 2007 mainly as Adult cardiac ECMO but later on we started doing even respiratory & paediatric ECMO. From 2010 onwards we had our mobile ECMO team & we started doing an outreached ECMO in various tertiary centres all over India. We analysed our data of ECMO in respiratory failure from January 2010 to November 2018 and we compared outcome & the ECMO run data in H1N1 & non H1N1 respiratory failure.
It is a Retrospective analysis of data collected of the patients with acute respiratory failure managed on ECMO by our centre from January 2010 to November 2018. The patient population was divided in two groups for the analysis one group was H1N1 positive infection while second group is of all respiratory failure patients which were non H1N1. The second group even has the patient with acute respiratory failure with pre & post lung transplant.
The total 169 patients of respiratory failure were treated with ECMO during specified period. Out of these 169 patients, 81 patients' falls in group A of H1N1 positive infection & remaining 88 patients fall in group B of Non H1N1 group. The common causes of acute Respiratory failure in non H1N1 group are given in Table 1.
These all patients were treated by our ECMO unit from the period January 2010 to November 2018. The Inclusion criteria for the ECMO were 
- PF ratio of less than 100
- Type II respiratory failure with pH less than 7.2 for more than 6 hours
- Ventilatory induced Lung Injury in terms pneumothorax & bronchopleural fistula.
The Exclusion criteria were
- Respiratory failure secondary to cardiac cause
- IC bleed
- Un-witnessed cardiac arrest.
After qualifying the inclusion criteria most of the patients were treated with VV ECMO. However 6 patients do required V-AV ECMO for initial hemodynamic instability which later on converted to VV ECMO after hemodynamic stability. All patients were cannulated by seldinger technic except 2 who required to undergo semi seldinger technic (semi open). All the patient were cannulated with drainage cannula in Femoral & return in Jugular except 6 patient (5 paediatric patient were cannulated with Double lumen Jugular cannula & one adult was managed with both femoral for drainage & return cannula as he had bilateral neck cellulitis). All the patients were managed with standard ELSO guidelines for management of VV ECMO. Anticoagulation was achieved with Heparin with the bolus dose of 70 – 100 units/kg at the time of cannulation followed by heparin Infusion 10 units/kg/min. Anticoagulation was monitored by ACT & APTT. Target ACT was around 160 s & target APTT was around 60 – 80 s. In those patients who had undergone V-AV ECMO, target ACT was around 180–200 s.  After initiation of ECMO, all the patients were managed with rest ventilatory settings on ECMO with Peak pressures restricted to 25, PEEP of 10, RR – 10/min FiO2 30 & I: E ratio 1:1.5. Exception to this settings were the patient with Barotrauma where the peak pressure was restricted to less than 20 & PEEP adjusted as per the tolerance ranging from 4 to 6. All patients who survived were gradually weaned off with standard guideline of decreasing ECMO FiO2 gradually followed by decreasing sweep gas. All those with VV ECMO were decannulated by just pulling the cannula out & with Horizontal matrix stiches on skin, no vascular repair done. Those who had V-AV ECMO were surgically decannulated with vascular repair.
The detailed data was collected of each patient & even submitted with ELSO database. Data were collected with reference to
- Date of admission, intubation & initiation of ECMO
- Date off ECMO, Ventilation & date of discharge or death
- Parameters at the time of initiation & after 24 hour of initiation like PF ratio, pH, PCO2 level, inotropic score, etc.
- Complications if any
- Outcome with cause of mortality
The data was then analysed with primary end point of outcome (see Table 2) (see Fig. 1) & secondary endpoint of length of stay on ECMO (see Table 3). The comparison of H1N1 VS non H1N1 respiratory failure on ECMO with reference to outcome & ECMO run was done. Further metaanalysis was done with comparing initiation parameters, complications & cause of death (see Table 3).
The overall survival remained around 40.8% in our patient of respiratory failure. There was not much statistically significance difference in the survival in both the groups (40.74 vs. 40.90 in H1N1 group & Non H1N1 group respectively). However there was a significant difference in the length of stay of ECMO in survivals. The average length of stay of survivals on ECMO in H1N1 group remained much more than in non H1N1 group (18.78 vs. 9.5 days respectively). Long run ECMO more than 30 days is seen in H1N1 (7 patients) with good survival (71.42%). There was no significant difference in parameters at the time of initiation (like PF ratio & PCO2 level) in both the groups (see Fig. 2). However on met analysis we found that patient with type II respiratory failure (high PCO2 > 45) at the time of initiation had less survival in non H1N1 group (33%) vs. those with only hypoxia but normal PCO2 (72%). However, in H1N1 group there was not much difference in survival type II & type I respiratory failure (40% vs. 42%).
In both the groups' common cause of mortality remained sepsis, which was nearly in the 60% of the patient who died. The incidence bleeding (major or minor) was almost two times in Non H1N1 group than H1N1 group (11.53% vs. 6.25% respectively). However, the incidence of IC bleed & Brain dead was significantly high (almost two times) in H1N1 group compared to Non H1N1 (14.5% vs. 7.69%) (see Figs. 3 and 4.).
On Further meta-analysis of non H1N1 group (see Table 4), the best survival was seen in patient with Dengue, Malaria & Leptospirosis (more than 60%) (see Fig. 5). In our study 13 patients (7.69%) were of malaria, Leptospirosis & dengue with the survival of 9 out of 13 (69.23% survival). However, 81/169 patients were of H1N1 infection. An average length of stay on ECMO in Malaria, Dengue & Leptospirosis was less (only 8–9 days) with lesser incidences of complications. In short, ECMO remains an effective modality of treatment for refractory hypoxia secondary to some tropical infections like Malaria, Dengue & Leptospirosis. These infections are much more rampant in India, some of Asian countries & Africa compared to H1N1 infections. However ECMO is still much underutilized modality (only nearly 8% of the cases are from this group).
ECMO is effective therapeutic modality in both Non H1N1 & H1N1 respiratory failure with average survival is around 41% in our centre. The length of stay on ECMO is much shorter in Non H1N1 respiratory failure compared to H1N1 patients. Survival with ECMO in tropical infections like Malaria, Dengue & Leptospirosis is more than 60% but only fewer patients are treated with ECMO. More awareness & papers needs to be published on these substrates of patients. Multicentre data Analysis on these substrates of patient may be of much utility & will be useful in increasing awareness & thereby number of cases benefitted with ECMO.
Conflict of interest
Thanks to our entire ECMO team who helped us developing the ECMO program in our centre & also for data collection.
 Zapol WM, Snider MT, Hill JD, et al. Extracorporeal Membrane Oxygenation in severe acute respiratory failure: a randomized prospective study. JAMA 1979:2193-2196.
 Venkat Goyal, Pranay Oza. History & development of ECMO. ECMO - theoretical manual. India: s.n., vol. 2,2; 2012. p. 11-22.
 Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy & Economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) a multicentre Randomized control trial. Lancet 2009.
 Magazine Rahul, Shobitha R, Umesh G, et al. Epidemiological profile of acute respiratory distress syndrome patients: a tertiary care experience. Lung India 2017;34(1):38-42.
 Bhadade RR, de Souza RA, Harde MJ, Khot A. Clinical characteristics and outcomes of patients with acute lung injury and ARDS
. J Postgrad Med 2011;57:286-290.
 Pooboni Suneel. Extracorporeal membrane oxygenation in the tropical world: disease-specific solutions and challenges. J Cardiac Crit Care TSS 2017;21:113-114.
 Murray CJL. Global malaria
mortality between 1980 and 2010: a systematic analysis. Lancet 2012;379:413-431.
 Key points: World malaria
report 2017. WHO regional website. [Online]; 2017.
 Venkat Goyal, Pranay Oza. Venovenous ECMO. ECMO - theoretical manual. India: s.n., vol. 2,6; 2012. p. 77-90.
 Venkat Goyal, Pranay Oza. Protocol for heparinization. ECMO practical manual. India: s.n.; 2010, p. 48-49.