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Extracorporeal Membrane Oxygenation as Salvage Therapy in the Peripartum Period: A Case Series

Patel, Sameer*; Loveridge, Robert*; Willars, Chris; Vercueil, Andre; Best, Thomas; Auzinger, Georg

Author Information
doi: 10.1097/MAT.0000000000001120
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Abstract

In 2017, the World Health Organization reported that approximately 295,000 women died of complications related to pregnancy or during the peripartum period.1 Despite considerable advances in maternity care provided by highly trained and motivated professionals, there was an increase in the overall maternal death rate in the United Kingdom between 2011–2013 and 2014–2016, with maternal deaths from direct causes remaining unchanged between 2011–2013 and 2014–2016,2 whereas the rate of indirect deaths remains high, with no significant change since 2003. Thromboembolic and cardiovascular diseases are the leading causes, respectively.2 Worryingly, even in developed countries with high-quality maternity services and low maternal mortality and morbidity rates, adequate maternal health is still not universally and consistently delivered. In the United States, the number of reported pregnancy-related deaths rose from 7.2 deaths per 100,000 live births in 1987 to a peak of 18 deaths per 100,000 live births in 2014, with a significant proportion considered preventable.3 A lack of access to quality skilled care before, during, and after childbirth is considered to be partially responsible, in combination with an increase in the number of complicated pregnancies, with mothers having more serious underlying medical conditions or having poorer general health.1

Even with optimal care, unexpected complications can result in catastrophic consequences. In such cases, all possible interventions should be explored and attempted, including the use of more novel and highly invasive advanced life support technologies. Extracorporeal membrane oxygenation (ECMO), a form of extracorporeal life support (ECLS), is one such technology.

Despite a lack of current guidelines on the use of ECMO during or after pregnancy,4,5 the successful use of veno-venous (V-V) ECMO during the peripartum period is well documented, particularly after the swine flu pandemic in 20096 and 2010.7 Several observational studies have reported patients successfully supported with ECMO during pregnancy and during the postpartum period, and a recent systematic review of ECLS in pregnancy determined that survival in patients who required V-V ECMO during pregnancy was as high as 78% (32/41) for the mother and 69% (27/39) for the fetus,8 demonstrating its feasibility and effectiveness in this group of patients.

Veno-arterial (V-A) ECMO use, on the other hand, is less frequently indicated and reported, but indications include peripartum cardiomyopathy, refractory arrhythmias, massive pulmonary embolism (PE), and even local anesthetic toxicity.8,9

Additional indications include extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest4 as a means to restore systemic perfusion until return of spontaneous circulation (ROSC), and subsequently while awaiting myocardial recovery, if recovery is a possibility.

We report the successful use of ECMO as a salvage rescue therapy in three very different cases of peripartum morbidity (Table 1).

Table 1. - Summary of Peripartum Patients Supported with ECMO in Our Institution
Pregnancy Status at the Time of ECMO Initiation Indication for ECMO Mode No-flow Time (min) Low-flow Time (min) Pre-ECMO* Days on ECMO Maternal Outcome (Hospital Discharge) Fetal Outcome
pH Lactate (mmol/L) SOFA
Case 1 Postpartum
3 weeks
Refractory CS post OOHCA V-A 0 88 6.5 18 16 5 Alive Alive
Case 2 Postpartum
3 days
HELLP V-V N/A N/A 7.27 8 21 9 Alive Alive
Case 3 Postpartum
4 weeks
Refractory OOHCA (PPCM) V-A (ECPR) 3–4 116 6.7 11 17 9 Alive Alive
*Worst physiologic parameter within preceding 6 hours of ECLS.
†Diagnosed with SCAD post hospital discharge.
CS, cardiogenic shock ECLS, extracorporeal life support; ECMO, extracorporeal membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation; HELLP, hemolysis, elevated liver enzymes, low platelets; N/A, not applicable; OOHCA, out of hospital cardiac arrest; PPCM, peripartum cardiomyopathy; SCAD, spontaneous coronary artery dissection; V-A, veno-arterial; V-V, veno-venous.

Ethics approval for the reporting of anonymous data was given by the South East London Research Ethics Committee.

Case 1

A 36-year-old woman with a history of hypertension in pregnancy, but otherwise fit and well, presented to the emergency department (ED) 3 weeks after delivery by cesarean section. She had a witnessed collapse at home and soon after arrival of the ambulance service suffered a cardiac arrest with immediate commencement of cardiopulmonary resuscitation (CPR). Her initial cardiac rhythm was ventricular fibrillation (VF) treated with electrical cardioversion, followed by pulseless electrical activity arrest and then asystole. Automated CPR with a LUCAS (Jolife AB, Lund, Sweden) mechanical chest compression device was continued en route to hospital where she achieved ROSC after a total of 88 minutes. At that time, profound metabolic disarray was present, with pH 6.5, base excess –32 mEq/L and lactate 18 mmol/L. Minimal cardiac output was maintained using a high-dose adrenaline infusion. Cardiac contractility on transthoracic echocardiography (TTE) in ED was severely impaired, with a survival after V-A ECMO (SAVE) score10 of –14 (and predicted survival of less than 18%). A decision was therefore made to commence peripheral V-A ECMO to provide circulatory support for refractory cardiogenic shock using a standard cannulation technique (Table 2). Upon establishment of ECMO flow, there was a rapid improvement in oxygenation, and weaning of the adrenaline infusion. She was cooled to 34°C for postcardiac arrest neuroprotection and underwent standard postcardiac arrest management and investigations. Coronary angiogram was not performed at the time because of bleeding and dissection of the superficial femoral artery requiring vascular surgery from attempted distal leg perfusion cannula insertion. Electroencephalogram on day 1 was largely unremarkable, but computed tomography (CT) scan on day 4 demonstrated severe, diffuse hypoxic ischemic brain injury, with intraventricular hemorrhage and early obstructive hydrocephalus.

Table 2. - ECMO Cannulation Characteristics
BSA (m2) Drainage Cannula Return Cannula Reperfusion Cannula Initial ECMO Flow (L/min)
Case 1 1.64 21 Fr RFV 15 Fr LFA 8.5 Fr 3.2
Case 2 2.13 27 Fr DL RIJV N/A N/A 4
Case 3 1.77 23Fr LFV 15Fr RFA 8.5Fr 3.5
BSA, body surface area; DL, dual lumen cannula; ECMO, extracorporeal membrane oxygenation; Fr, French; LFA, left femoral artery; LFV, left femoral vein; N/A, not applicable; RFA, right femoral artery; RFV, right femoral vein; RIJV, right internal jugular vein.

Over subsequent days, she remained sedated and mechanically ventilated. Her metabolic, cardiovascular, and respiratory parameters improved with time. She was decannulated after 5 days of ECMO support with improving cardiac function, and she remained stable off ECMO. Subsequent cardiac magnetic resonance imaging revealed her cause of arrest as spontaneous coronary artery dissection (SCAD) of the right coronary artery and was treated conservatively. On intensive care unit discharge, she underwent further intensive neurorehabilitation, and 6 months after discharge she was at home caring for her child, with almost complete neurologic recovery and only mild short-term memory deficits and low mood, consistent with cerebral performance category (CPC) 2.

Case 2

A 34-year-old primigravida mother developed hyperlactatemia and distributive shock requiring emergency exploratory laparotomy day 1 post emergency cesarean section for preeclampsia.

She was transferred to our institution for tertiary hepatology management after laparotomy excluded bowel ischemia, but revealed an ischemic liver and ascites. On admission, she had severe liver dysfunction (Table 3) with evidence of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (peak aspartate aminotransferase 4,168 IU/L, bilirubin 316 µmol/L), a profound coagulopathy, and persistent hyperlactatemia >8 mmol/L despite resuscitation and high-volume continuous veno-venous hemodiafiltration. She was listed for emergency liver transplantation (ELT) and commenced on therapeutic plasma exchange as an extracorporeal bridge to transplantation in view of rising vasopressor requirements and profound coagulopathy. Because of refractory hypoxia (Murray score 3.75, PaO2/FiO2 ratio 67.5 mmHg), and suboptimal CO2 control for neuroprotective management of cerebral edema, she was deemed “too sick to transplant,” and a decision was taken to support her with V-V ECMO. A 27 Fr dual lumen cannula was placed in her right internal jugular vein under transesophageal echocardiography guidance. Cardiopulmonary function improved dramatically, facilitating transplantation, and 24 hours later she was successfully bridged to v on ECMO with excellent immediate graft function. She was successfully weaned and decannulated after 9 days of ECMO and discharged home on day 43.

Table 3. - Pre- and Post-ECMO Results
Pre-ECMO 24 Hours Post ECMO At Decannulation
Bilirubin (μmol/L) 278 316 76
AST (IU/L) 4,156 2,720 92
Creatinine on CVVHDF (μmol/L) 149 150 183*
Na 149 151 136
INR 5.87 1.55 1.14
Platelets 49 44 49
Albumin 25 26 26
Lactate (mmol/L) 8 6.3 1.7
APACHE II 38 N/A N/A
SOFA 21 18 12
PaO2/FiO2 ratio (mm Hg) 67.5 N/A N/A
Murray Score 3.75 N/A N/A
*Off CVVHDF.
APACHE II, acute physiology and chronic health evaluation II score; AST, aspartate aminotransferase; CVVHDF, continuous veno-venous hemodiafiltration; ECMO, extracorporeal membrane oxygenation; INR, international normalized ratio; SOFA, sequential organ failure assessment.

Case 3

A 42-year-old lady 4 weeks postpartum (para 9, gravida 9) with no significant medical history was admitted after a collapse at home in the presence of her children. On arrival of emergency medical services, her initial presenting rhythm was noted to be asystole, and she was resuscitated as per advanced life support guidelines. CPR was continued with the LUCAS mechanical chest compression device. She subsequently developed recurrent VF and received seven direct current shocks. Further collateral history suggested that she may have had intermittent chest pain in the week before the arrest. On arrival in the ED, she remained in refractory VF and pulseless VT arrest, which were treated according to advanced life support guidelines. She was thrombolyzed with recombinant tissue plasminogen activator for a presumed massive PE as bedside transthoracic echocardiography (TTE) demonstrated a dilated right ventricle, in addition to a severely impaired and dilated left ventricle, with peripartum cardiomyopathy the main other differential diagnosis at this point. She was also treated for refractory arrhythmia with magnesium sulfate, as well as amiodarone and lignocaine infusions.

In view of her young age and postpartum status, a decision was made to proceed with ECPR. Arterial blood gases showed severe lactic acidosis with an arterial lactate level of 11 mmol/L and pH 6.7.

The patient was commenced on ECLS (23 Fr multistage drainage cannula via femoral vein and a 15 Fr single-stage return cannula via the femoral artery), with a total no-flow and low-flow time of approximately 120 minutes (no-flow time 3–4 minutes), and the recurrent refractory VT/VF subsequently subsided. The patient underwent diagnostic coronary angiogram to exclude obstructive coronary lesions or coronary dissection. Infusions of vasoactive medications, including noradrenaline, milrinone, and low-dose levosimendan, as well as low-dose adrenaline were continued. Lactic acidosis gradually improved with complete normalization of lactate levels within hours, and there was no immediate need for renal replacement therapy in the presence of preserved urine output.

All investigations, including microbiology, virology, and CT pulmonary angiogram, were negative, leaving peripartum cardiomyopathy as the main differential diagnosis. Her cardiac status slowly improved to an ejection fraction (EF) of approximately 25%. She was successfully weaned off all vasoactive medication and was eventually decannulated from ECMO on day 9.

Electroencephalogram and CT of the brain as part of her neuroprognostication showed findings consistent with severe hypoxic brain injury. Somatosensory evoked potentials were thus conducted and demonstrated absent N20 potentials, consistent with the worst possible neurologic outcome. However, as she had preserved brain stem function, it was conceded that a diagnosis of persistent vegetative state or minimally conscious state could not be made at such an early stage, and she was discharged from hospital to a nursing home, with CPC score of 4.

Discussion

Pregnancy-related morbidity and mortality continues to remain high, particularly in the developing world, but also in developed countries such as the United States and even the United Kingdom. Hemorrhage, cardiovascular and coronary conditions, and cardiomyopathy make up the three most common causes of pregnancy-associated deaths, followed by sepsis and embolism.3 Although a number of deaths are potentially deemed avoidable with appropriate education and infrastructure, others, such as peripartum cardiomyopathy, are not and can be extremely challenging to diagnose and manage.

The past decade has seen a significant surge in the use of ECMO in adults as a mode of advanced life support. Its primary role is in the management of potentially reversible, life-threatening forms of respiratory or cardiac failure, unresponsive to conventional therapy. It has also been used in patients with irreversible cardiac or respiratory disease as a bridge to potential heart or lung transplant, or as a bridge to other forms of more definitive mechanical cardiac support, such as ventricular assist device therapy.

Beyond classical indications, such as the most severe forms of acute respiratory distress syndrome, cardiogenic shock of varying etiology, and failure to wean from bypass after cardiac surgery, ECMO use has broadened to now include presentations previously considered to constitute relative or absolute contraindications, such as malignant hematological disease processes, multitrauma including traumatic brain injury, acute liver failure, and peri-liver transplantation.11–13 Despite the establishment of nationally commissioned respiratory ECMO centers in the United Kingdom, there is an unmet need in the care and support of some of these subspecialty populations in frontline EDs and acute care trusts around the country, and indeed internationally, who do not have ECMO capabilities within their institutions. There are perhaps a number of reasons for this including the following: potentially perceived contraindications, e.g., liver failure patients who are coagulopathic and therefore may bleed excessively or uncontrollably on ECMO; or in the case of ECPR an inability to provide support because of the time-critical nature of refractory cardiac arrest in non-ECMO capable hospitals; or as is the case in places such as the United Kingdom being denied access to commissioned respiratory centers because of a lack of onsite expertise in these centers from associated medical or surgical specialties, thus limiting specialist care available to these patients.

We report three very different indications for ECLS in patients with profound morbidity associated with pregnancy, all of whom would not have survived with conventional intensive care management alone in a non-ECMO center. Cases 1 and 2 survived with CPC 2 and 1, respectively, indicating the best possible survival outcome with good neurology. The second case is, to the best of our knowledge, the first reported case of the use of ECMO as a bridge to ELT in an adult with peripartum acute liver failure. Although the third case survived with poor neurologic outcome, predictable because of the prolonged no-flow and low-flow times before ECMO was eventually initiated, use of ECPR was felt to be appropriate in view of her recent pregnancy and large number of dependents, to offer an opportunity of potential recovery.

Spontaneous Coronary Artery Dissection

SCAD prevalence remains unknown. Having previously been thought to be a rare condition, it is thought to make up as much as 1–4% of acute coronary syndrome (ACS) cases.14 The development of a false lumen within the coronary artery wall, either from an intimal tear or through spontaneous hemorrhage wall, results in compression of the true lumen compromising coronary flow resulting in myocardial ischemia or infarction. Pregnancy-associated SCAD (p-SCAD) is the most common cause of pregnancy-associated myocardial infarction and usually occurs within the first 4 weeks of delivery (predominantly within the first week), but can occur during any trimester of the pregnancy. Diagnosis is usually made on coronary angiogram, although alternative imaging modalities such as cardiac CT angiography or magnetic resonance angiography may be used. Conservative management has been shown to result in 70–97% of lesions healing, most within 1 month of the event. For those with ongoing ischemia or hemodynamic instability, percutaneous intervention may be an option although several studies including the Mayo Clinic series15 have demonstrated adverse outcomes after technical complications. Observational data on performing coronary artery bypass grafts similarly have not demonstrated an advantage beyond conservative management. Despite lower mortality rates in p-SCAD compared from ACS, mortality is not insignificant at 1–2%, and although the use of mechanical circulatory support (MCS) devices such as ECMO is rare, case reports have described the use of MCS and ECMO as a bridge to recovery or even heart transplantation.16

Pregnancy-Associated Liver Disease

Pregnancy-associated liver disease is rare, affecting up to 3% of pregnant women and is associated with significant morbidity and mortality for both mother and infant when severe.17 Rapid diagnosis and treatment is essential for optimal outcomes. Acute fatty liver of pregnancy, preeclampsia, and HELLP syndrome are three of the most common pregnancy-related liver diseases seen in late pregnancy. Usually, early recognition, initiation of supportive care, and rapid delivery of the fetus improve prognosis for both the mother and the baby. However, in a minority of cases, liver dysfunction is profound and the only treatment is super urgent liver transplantation. Even in this small group requiring life-saving ELT transplantation is not always possible if the patient is deemed “too sick to transplant.” In one single-center study, 24% of those listed for ELT died before transplantation occurred, with 5% of those listed found to be too critically unwell to proceed.18

In the liver transplantation population, advances in surgical techniques and perioperative care have led to improved outcomes in recent years, and as a result the use of ECMO to bridge patients to, or provide intra- or postoperative support after liver transplantation is relatively novel and not widely reported. ECMO has been shown to be feasible in the postliver transplant group who develop postoperative complications, such as refractory hypoxia,12 cardiogenic or septic shock, or even cardiac arrest perioperatively.19

Peripartum Cardiomyopathy

Peripartum cardiomyopathy is defined as a cardiomyopathy with reduced EF <45% presenting toward the end of pregnancy, or in the months after delivery, in a woman without previously known structural heart disease. Most cases appear to occur in the first weeks post delivery, with a number of potential causes proposed, including viral myocarditis, nutritional deficiencies, autoimmune disease, microchimerism, and hemodynamic stresses. Women typically present with signs and symptoms of congestive heart failure. However, a significant number of patients have more catastrophic presentations including sudden death because of arrhythmias. It comes as no surprise that managing such patients can be extremely challenging. Mortality from peripartum cardiomyopathy ranges from 1.3% to 4%. With an incidence ranging from 1 in 1,000–4,000 in various parts of the world, this potentially represents a significant number of mothers who are dying unexpectedly. The use of MCS devices may be necessary for the management of refractory cardiogenic shock, as a “bridge to recovery.”20 A recent French case series demonstrated that when considered early, MCS is safe and effective in these patients, with 50% survival in their institution.9 Despite these encouraging outcome figures, refractory cardiogenic shock in this population remains a life-threatening condition.

Conclusions

Pregnancy-related morbidity and mortality continues to be high, and although a number of deaths are potentially deemed avoidable, others such as refractory hypoxia and peripartum cardiomyopathy are not, and can be extremely challenging to diagnose and manage. V-V or V-A ECMO is feasible in these patients and should ideally be considered early when conventional therapy is failing with referral to centers with ECMO capabilities if in a non-ECMO capable center, or as a salvage rescue therapy when it has failed.

Acknowledgment

Patient consent was obtained from all three patients or their next of kin.

References

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16. Jorge-Pérez P, García-González MJ, Ávalos-Pinto RM, et al. Spontaneous coronary dissection and cardiogenic shock requiring mechanical circulatory support in a non-transplant center. Int J Cardiol 2016; 221:629–630.
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Keywords:

ECMO; maternal morbidity; maternal mortality; pregnancy complications; pregnancy-related liver disease

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