ASAIO Journal 2015
Case Series
Modern Use of Extracorporeal Life Support in Pregnancy and Postpartum Nirmal S. Sharma,* Keith M. Wille,* Scott C. Bellot,† and Enrique Diaz-Guzman*
Extracorporeal membrane oxygenation (ECMO) use during pregnancy and the postpartum period are thought to be associated with an increased risk for maternal or fetal bleeding complications. We present our recent institutional experience in managing pregnant and postpartum patients with ECMO. We also performed a literature review of modern use of ECMO in pregnant and postpartum patients utilizing Pubmed and Embase databases. ECMO was used for severe cardiopulmonary failure due to multiple conditions. Based on published reports, overall maternal and fetal survival on ECMO were 80% and 70%, respectively. Mild-to-moderate vaginal bleeding was reported in a few cases, with rare occurrences of catastrophic postpartum hemorrhage. There was no consensus on an optimal anticoagulation strategy in these patients, though most preferred to keep anticoagulation at lower therapeutic levels. We conclude that ECMO, in wellselected pregnant and postpartum patients, appears to be safe and associated with low risk of maternal and fetal complications. ASAIO Journal 2015; 61:110–114.
Extracorporeal life support use in pregnancy is uncommon, and there are concerns related to an increased risk of maternal and fetal bleeding, hemolysis, and thrombotic complications associated with mechanical pump trauma and the use of systemic anticoagulation. Currently, there are no guidelines for ECLS use during pregnancy or postpartum, and there are limited reports in the literature describing the efficacy and safety of ECLS in this population. The vast majority of recent reports are related to ARDS due to influenza (H1N1).3 We describe our institutional experience with ECLS use in pregnant and postpartum women, and present a systematic review of the literature describing its use in this population. Methods We performed a series of computerized librarian-assisted searches using the databases PubMed and Embase (from January 2009 to February 2014). The search strategy was intended to include reports describing modern use of ECLS during the last 5 years. We restricted the results to articles published in English language. The PubMed searches were performed using the following Medical Subject Heading terms: 1) Pregnancy AND ARDS; 2) Pregnancy AND (extracorporeal oxygenation OR extracorporeal assist); 3) Post-Partum AND (extracorporeal oxygenation OR extracorporeal assist). The search strategy yielded 128 results in total. We then manually selected only reports that included the use of ECLS/ECMO during pregnancy or postpartum, and this search yielded 31 reports accounting for a total of 67 patients supported with this technology.
Key Words: extracorporeal membrane oxygenation, pregnancy, acute respiratory distress syndrome, postpartum, postpartum cardiomyopathy
Extracorporeal life support (ECLS) refers to the use of extra-
corporeal cardiopulmonary bypass in patients with cardiac or respiratory failure. The term extracorporeal membrane oxygenation (ECMO) is preferred for patients who only require respiratory support, although both terms are sometimes used interchangeably.1 ECMO has been used as a rescue therapy in patients with respiratory failure, including those with refractory hypoxemia due to acute respiratory distress syndrome (ARDS). Extracorporeal life support is commonly employed in patients with circulatory arrest or significant cardiac dysfunction. Over the last 5 years, there has been a substantial increase in the use of ECMO and ECLS for patients with cardiorespiratory failure, associated with an improvement in patient outcomes.2 For the purpose of this article, we will be referring to all cases of ECLS or ECMO as ECLS.
Results/Data Section Our experience: Case Reports We describe four pregnant patients who presented with respiratory distress and subsequently developed cardiorespiratory failure requiring ECLS therapy. Median age of the patients at presentation was 26 years. Most common initial presenting symptoms in all patients were malaise, dyspnea, and cough. Two patients were pregnant when ECLS was initiated, and two were postpartum. Indications for ECLS and type of support are shown in Table 1. Before ECLS, patients had received mechanical ventilation (MV) for an average of 4 days. Mean PaO2/FiO2 ratio at ECLS initiation was 51 mmHg. A double lumen internal jugular catheter (DLC) was used for veno-venous (V-V) ECMO cannulation, whereas femoral cannulation was preferred for veno-arterial (V-A) ECMO support. Anticoagulation therapy with heparin was followed in all patients according to our program guidelines (Table 2). Activated clotting time (ACT), activated partial thromboplastin time (aPTT), and thromboelastography were maintained between 160 and 180 seconds, 50 and 80
From the *Division of Pulmonary, Critical Care, and Sleep Medicine, and the †Department of Cardiothoracic Surgery, University of Alabama, Birmingham, Alabama. Submitted for consideration April 2014; accepted for publication in revised form August 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Enrique Diaz-Guzman, Lung Transplant and Adult ECMO program, University of Alabama, AL 1102 Jefferson Tower, 625, 19th Street South, Birmingham, AL 35294-7410. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000154
110
6
ECLS, extracorporeal life support; ARDS, acute respiratory distress syndrome; STEMI, ST elevation myocardial infarction.
12 52 Alive Alive V-V Peripartum cardiomyopathy ARDS unknown likely influenza Postpartum (Day 2)
V-A Cardiogenic shock likely viral Pregnant (34 weeks)
V-V Influenza (A) ARDS Postpartum (Day 1)
111
seconds, and reaction time 2.5–3.0 × normal, respectively.4 Although none of the patients developed severe hemorrhage, we observed occurrences of mild-to-moderate bleeding in two patients requiring blood transfusions to maintain a hematocrit more than 28%. One patient had mild hemorrhage around the tracheostomy and DLC cannula sites, while another patient had moderate postpartum uterine hemorrhage which resolved without intervention. In addition, one patient had thrombosis of the oxygenator membrane that did not require circuit change. Vaginal delivery of the fetus on ECLS was performed in one case. The other pregnant patient continued her pregnancy without any complications. Extracorporeal life support referral was made early in the course of MV in three patients (average days to referral 3–4 days from initiation of MV), while one had a relatively delayed referral due to initial improvement on conventional MV (Day 10). Early tracheostomy was performed in three patients to help with reduction in use of sedation. Mean duration on ECMO was 5 days. All patients survived hospitalization and were discharged without significant morbidity. Fetal survival was 75%.
Day 2
6 16 Alive
Stillborn
50
Day 1
4 Day 2 24 Alive
Alive
54
Day 10 20 Alive
Minor bleeding: tracheostomy site, ECMO catheter site Minor bleeding: vaginal bleeding STEMI, vaginal bleeding, clot in circuit Minor bleeding: vaginal bleeding, tracheostomy site bleeding V-V Mycoplasma ARDS Pregnant (25 weeks)
Complications Etiology/Indication Pregnant/Postpartum
Alive
47
Day ECMO Initiated After MV PEEP (cm of water) at initiation of ECMO PaO2 (mmHg) at initiation of ECMO Fetal Outcome Maternal Outcome Circuit (V-A/V-V)
Table 1. Description of Pregnant and Postpartum Patients Supported with ECLS at our Center
5
MODERN USE OF ECLS IN PREGNANCY AND POSTPARTUM
Days on ECMO
Review of Literature We found 31 published reports over the last 5 years describing ECLS use during pregnancy and postpartum, with a total of 67 patients supported with this technology: 15 reports of V-V ECMO, 16 reports of V-A ECMO, and 1 report of a lung assist device5 (Table 3). Overall, maternal and fetal survival with ECLS, based on published reports, were 80% and 70%, respectively. A query of the extracorporeal life support organization (ELSO) database revealed no additional cases of ECMO use in pregnancy or postpartum, largely due to a lack of adequate coding in the database. Indications for ECLS use in the above cases included severe ARDS, postpartum cardiogenic shock, and amniotic fluid embolism (Table 3). In most studies, anticoagulation for ECLS in pregnant and postpartum patients was maintained at the lower therapeutic level and adjusted by serial monitoring of aPTT or ACT levels. However, there was no consensus on the optimal range for maintaining anticoagulation. ACT ranged from 140 to 220 seconds and APTT from 50 to 80 seconds in various studies.9,10,16–18,28,29 The most common site of bleeding reported was around the tracheostomy and ECMO cannula site. A few cases reported mild-to-moderate amounts of postpartum vaginal bleeding, with one reporting catastrophic postpartum hemorrhage.3,19 Blood transfusions and albumin were given in most reports to maintain optimal circuit flow and hematocrit above 30%. Delivery of the fetus while on ECLS was mostly deferred, but in one case the fetus was successfully delivered via cesarean section while the mother remained on ECLS.20 Arrhythmia ablation and heart valve repair were also performed successfully on ECLS in many cases.12–15,27 Patients with severe bleeding, including pulmonary hemorrhage and postpartum bleeding, were supported by ECLS with favorable outcomes, suggesting a good safety profile with current technology available.10 Discussion A recent report based on a national database described a significant increase in ECLS utilization and improved outcomes,
112 SHARMA et al. Table 2. Anticoagulation Monitoring for Pregnant Patients on ECMO at our Institution
ACT, activated clotting time.
with survival rates of 58% for respiratory and 40–49% for cardiac patients.2 Extracorporeal life support therapy in nonpregnant patients has been shown to be safe when used in carefully selected individuals.34 Extracorporeal life support may help prevent maternal or fetal hypoxemia in pregnant patients with
severe cardiac or respiratory failure, when conventional methods of support fail to provide adequate oxygen delivery. Our review of the literature shows that ECLS in pregnancy appears to be uncommon with only 67 patients reported during the last 5 years. These results suggest that ECLS remains underutilized
Table 3. Use of ECLS in Pregnancy and Postpartum – A Summary of the Cases Reported in the Literature
Reference
No of Patients
6–8
3
9
1 1 1
10 11
33% pregnant and 66% Postpartum Postpartum Pregnant Postpartum
27
1
Pregnant 75% pregnant and 25% postpartum 70% pregnant and 30% postpartum Postpartum
28
1
Postpartum
29,30
2
31,32
2
50% pregnant and 50% postpartum Postpartum
33
1 1
Pregnant Pregnant
5 12–15
3,16–26
21
1 4
Pregnancy Status (%)
48
Indication for ECLS Amniotic fluid embolism Atonic uterine bleeding Pulmonary hemorrhage-related arrest Cerebral venous thrombosis/ respiratory failure ARDS: due to all trans retinoic acid Persistent arrhythmia/ cardiogenic shock H1N1 ARDS Severe mitral regurgitation due to infective endocarditis Takasubo’s cardiomyopathy/ cardiogenic shock Pulmonary embolus/right ventricular failure Postpartum cardiomyopathy/ cardiogenic shock Staphylococcal ARDS Cardiac arrest/post-ACLS/CPR
Survival
Mode of ECLS (V-A/V-V)
Maternal (%)
Fetal (%)
2 V-A and 1 V-V
100
100
100 100 100
100 0 100
100 100
0 50
92
74
V-A
100
100
V-A
100
100
V-A
100
100
V-A
100
50
V-V V-A
100 100
Unknown 0
V-A V-V V-V Lung assist V-A 3 V-A and 45 V-V
CPR, Cardio-pulmonary resuscitation; ECLS, extracorporeal life support; ARDS, acute respiratory distress syndrome; V-A, veno-arterial; V-V, veno-venous.
MODERN USE OF ECLS IN PREGNANCY AND POSTPARTUM
in pregnancy possibly due to concerns of increased bleeding in the mother and fetus.3,35 Nevertheless, we found only a few case reports of catastrophic bleeding, with overall maternal survival of pregnant and postpartum patients supported with ECLS similar to nonpregnant patients. At our institution, we routinely use ECLS to support patients with severe cardiopulmonary failure who fail to respond to conventional therapy. Most common indications include ARDS, severe pneumonia, status asthmaticus, pulmonary embolism, and cardiogenic shock. Pregnancy is not considered a contraindication for ECLS at our center. Pregnant patients are considered candidates if they have evidence of severe cardiopulmonary failure (PaO2/FiO2 ratio less than 100 mmHg after optimal positive end-expiratory pressure (PEEP) titration or cardiogenic shock compromising maternal and fetal survival). In case of hemorrhagic complications or evidence of fetal distress on ECLS, a cesarean section or vaginal delivery is offered to these patients. In addition, the obstetrical team performs intrauterine balloon tamponade for postpartum hemorrhage if indicated (none of our patients required this treatment). Moreover, we consider ECLS therapy in these patients if there is evidence of maternal or fetal viability and no major contraindications are present, such as severe uncorrectable coagulopathy (i.e., disseminated intravascular coagulation) and severe or uncontrollable active hemorrhage (i.e., uterine, gastrointestinal hemorrhage, etc.). Although none of our patients underwent cesarean section while receiving ECLS, reports in the literature suggest that the operation can be performed safely after a temporary suspension of anticoagulation.20,36 In addition, ECLS has been described in pregnant patients with severe pre-eclampsia, eclampsia, H- hemolysis, EL- elevated liver enzymes, LP- low platelets counts (HELLP) syndrome, and catastrophic antiphospholipid syndrome, although these pose a unique challenge as patients may have an increased risk for bleeding and thrombotic complications associated with refractory thrombocytopenia or hypercoagulable state.6,37,38 Finally, ECLS specialists should be aware of the possibility of amniotic fluid embolism in postpartum patients requiring ECLS, as this complication may be associated with a high rate of coagulopathy and bleeding, requiring continuous adjustment to anticoagulation parameters, transfusions, and hemorrhage control.6,39 Based on our limited experience and review of the available literature, we believe that ECLS can be used safely in well-selected pregnant and postpartum patients with severe cardiorespiratory compromise. We recommend early consultation with an ECLS center for pregnant patients with severe cardiorespiratory compromise to improve the chance of maternal and fetal survival. Our report is not without limitations. The number of cases that we reviewed only represents experience with ECLS over the last 5 years, and so it is possible that results may be different when analyzing ECLS use over previous decades. In addition, it is possible that we missed some cases that were not identified by our search engine. Finally, overestimation of survival with ECLS is possible due to publication bias from reporting only positive outcomes in the literature. We believe that additional information related to pregnant patients should be included in a national registry such as the ELSO database. This may provide a better understanding of the use and safety of ECLS in pregnant and postpartum women.
113
Conclusion Extracorporeal life support has been successfully used in pregnant and postpartum patients for a variety of indications without report of significant maternal or fetal morbidity or mortality. By carefully selecting patients and judiciously managing systemic anticoagulation, ECLS can be safely instituted in this cohort with successful outcomes. References 1. Conrad SA, Rycus PT, Dalton H: Extracorporeal Life Support Registry Report 2004. ASAIO J 51: 4–10, 2005. 2. Paden ML, Rycus PT, Thiagarajan RR; ELSO Registry: Update and outcomes in extracorporeal life support. Semin Perinatol 38: 65–70, 2014. 3. Nair P, Davies AR, Beca J, et al: Extracorporeal membrane oxygenation for severe ARDS in pregnant and postpartum women during the 2009 H1N1 pandemic. Intensive Care Med 37: 648– 654, 2011. 4. Oliver WC: Anticoagulation and coagulation management for ECMO. Semin Cardiothorac Vasc Anesth 13: 154–175, 2009. 5. Coscia AP, Cunha HF, Longo AG, Martins EG, Saddy F, Japiassu AM: Report of two cases of ARDS patients treated with pumpless extracorporeal interventional lung assist. J Bras Pneumol 38: 408–411, 2012. 6. Grimme I, Winter R, Kluge S, Petzoldt M: Hypoxic cardiac arrest in pregnancy due to pulmonary haemorrhage. BMJ Case Rep 2012. 7. Holzgraefe B, Broomé M, Kalzén H, Konrad D, Palmér K, Frenckner B: Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure. Minerva Anestesiol 76: 1043–1051, 2010. 8. Hou X, Guo L, Zhan Q, et al: Extracorporeal membrane oxygenation for critically ill patients with 2009 influenza A (H1N1)-related acute respiratory distress syndrome: Preliminary experience from a single center. Artif Organs 36: 780–786, 2012. 9. Itagaki T, Onodera M, Okuda N, Nakataki E, Imanaka H, Nishimura M: Successful use of extracorporeal membrane oxygenation in the reversal of cardiorespiratory failure induced by atonic uterine bleeding: a case report. J Med Case Rep 8: 23, 2014. 10. Jo YY, Park S, Choi YS: Extracorporeal membrane oxygenation in a patient with stress-induced cardiomyopathy after caesarean section. Anaesth Intensive Care 39: 954–957, 2011. 11. Kunstyr J, Lips M, Belohlavek J, et al: Spontaneous delivery during veno-venous extracorporeal membrane oxygenation in swine influenza-related acute respiratory failure. Acta Anaesthesiol Scand 54: 1154–1155, 2010. 12. Weinberg L, Kay C, Liskaser F, et al: Successful treatment of peripartum massive pulmonary embolism with extracorporeal membrane oxygenation and catheter-directed pulmonary thrombolytic therapy. Anaesth Intensive Care 39: 486–491, 2011. 13. Robertson LC, Allen SH, Konamme SP, Chestnut J, Wilson P: The successful use of extra-corporeal membrane oxygenation in the management of a pregnant woman with severe H1N1 2009 influenza complicated by pneumonitis and adult respiratory distress syndrome. Int J Obstet Anesth 19: 443–447, 2010. 14. Panarello G, D’Ancona G, Capitanio G, et al: Cesarean section during ECMO support. Minerva Anestesiol 77: 654–657, 2011. 15. Burrows K, Fox J, Biblo LA, Roth JA: Pregnancy and short-coupled torsades de pointes. Pacing Clin Electrophysiol 36: e77–e79, 2013. 16. Hansen AJ, Sorrell VL, Cooper AD, Moulton MJ: Postpartum rupture of the posteromedial papillary muscle. J Card Surg 27: 313–316, 2012. 17. Pagel PS, Lilly RE, Nicolosi AC: Use of ECMO to temporize circulatory instability during severe Brugada electrical storm. Ann Thorac Surg 88: 982–983, 2009. 18. Scherrer V, Lasgi C, Hariri S, et al: Radiofrequency ablation under extracorporeal membrane oxygenation for atrial tachycardia in postpartum. J Card Surg 27: 647–649, 2012.
114 SHARMA et al. 19. Sim SS, Chou HC, Chen JW, Ma MH: Extracorporeal membrane oxygenation in maternal arrhythmic cardiogenic shock. Am J Emerg Med 30: 1023.E3–1012.E5, 2012. 20. Peek GJ, Clemens F, Elbourne D, et al: CESAR: Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC Health Serv Res 6: 163, 2006. 21. Cunningham JA, Devine PC, Jelic S: Extracorporeal membrane oxygenation in pregnancy. Obstet Gynecol 108(3 Pt 2): 792– 795, 2006. 22. Koster AA, Pappalardo F, Silvetti S, et al: Cesarean section in a patient with non-compaction cardiomyopathy managed with ECMO. Heart Lung Vessel 5: 183–186, 2013. 23. Hanouna G, Morel N, Le Thi Huong D, et al: Catastrophic antiphospholipid syndrome and pregnancy: An experience of 13 cases. Rheumatology (Oxford) 52: 1635–1641, 2013. 24. Ecker JL, Solt K, Fitzsimons MG, et al: Case records of the Massachusetts General Hospital. Case 40–2012. A 43-year-old woman with cardiorespiratory arrest after a cesarean section. N Engl J Med 367: 2528–2536, 2012. 25. Manuel L. Ribeiro Neto M, Danai Khemasuwan M, Raed A. Dweik M. A case of concomitant pulmonary arterial hypertension and HELLP syndrome: How unique is it?. AJRCCM 2012; Abstract issue 2012: D68 Pulmonary vascular diseases: Clinical cases. 26. Gist RS, Stafford IP, Leibowitz AB, Beilin Y: Amniotic fluid embolism. Anesth Analg 108: 1599–1602, 2009. 27. Ho CH, Chen KB, Liu SK, Liu YF, Cheng HC, Wu RS: Early application of extracorporeal membrane oxygenation in a patient with amniotic fluid embolism. Acta Anaesthesiol Taiwan 47: 99–102, 2009. 28. Shen HP, Chang WC, Yeh LS, Ho M: Amniotic fluid embolism treated with emergency extracorporeal membrane oxygenation: A case report. J Reprod Med 54: 706–708, 2009. 29. Strecker T, Münch F, Weyand M: One hundred ten days of extracorporeal membrane oxygenation in a young woman with postpartum cerebral venous thrombosis and acute respiratory distress syndrome. Heart Surg Forum 15: 180–E181, 2012.
30. Wall CJ, Santamaria J: Extracorporeal membrane oxygenation: An unusual cause of acute limb compartment syndrome. Anaesth Intensive Care 38: 560–562, 2010. 31. Courouble P, Geukens P, Laarbaui F, Beauloye C, Van Caenegem O, Jacquet LM: Adult respiratory distress syndrome caused by 2009 H1N1 influenza during pregnancy: Success of ECMO for both the mother and the child. J Extra Corpor Technol 43: 75–78, 2011. 32. Dubar G, Azria E, Tesniere A, et al: French experience of 2009 A/ H1N1v influenza in pregnant women. PLoS One 5: e3112, 2010. 33. Grasselli G, Bombino M, Patroniti N, et al: Use of extracorporeal respiratory support during pregnancy: A case report and literature review. ASAIO J 58: 281–284, 2012. 34. Power CA, Van Heerden PV, Moxon D, Martindale G, Roberts B: Extracorporeal membrane oxygenation for critically ill patients with influenza A (H1N1) 2009: A case series. Crit Care Resusc 13: 38–43, 2011. 35. Welch SA, Snowden LN, Buscher H: Pandemic (H1N1) 2009 influenza, pregnancy and extracorporeal membrane oxygenation. Med J Aust 192: 668, 2010. 36. Arlt M, Philipp A, Iesalnieks I, Kobuch R, Graf BM: Successful use of a new hand-held ECMO system in cardiopulmonary failure and bleeding shock after thrombolysis in massive post-partal pulmonary embolism. Perfusion 24: 49–50, 2009. 37. Gevaert S, Van Belleghem Y, Bouchez S, et al: Acute and critically ill peripartum cardiomyopathy and ‘bridge to’ therapeutic options: A single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuousflow left ventricular assist devices. Crit Care 15: R93, 2011. 38. Smith IJ, Gillham MJ: Fulminant peripartum cardiomyopathy rescue with extracorporeal membranous oxygenation. Int J Obstet Anesth 18: 186–188, 2009. 39. Noah MA, Dawrant M, Faulkner GM, et al: Panton-Valentine leukocidin expressing Staphylococcus aureus pneumonia managed with extracorporeal membrane oxygenation: experience and outcome. Crit Care Med 38: 2250–2253, 2010.
Case Series
Modern Use of Extracorporeal Life Support in Pregnancy and Postpartum Nirmal S. Sharma,* Keith M. Wille,* Scott C. Bellot,† and Enrique Diaz-Guzman*
Extracorporeal membrane oxygenation (ECMO) use during pregnancy and the postpartum period are thought to be associated with an increased risk for maternal or fetal bleeding complications. We present our recent institutional experience in managing pregnant and postpartum patients with ECMO. We also performed a literature review of modern use of ECMO in pregnant and postpartum patients utilizing Pubmed and Embase databases. ECMO was used for severe cardiopulmonary failure due to multiple conditions. Based on published reports, overall maternal and fetal survival on ECMO were 80% and 70%, respectively. Mild-to-moderate vaginal bleeding was reported in a few cases, with rare occurrences of catastrophic postpartum hemorrhage. There was no consensus on an optimal anticoagulation strategy in these patients, though most preferred to keep anticoagulation at lower therapeutic levels. We conclude that ECMO, in wellselected pregnant and postpartum patients, appears to be safe and associated with low risk of maternal and fetal complications. ASAIO Journal 2015; 61:110–114.
Extracorporeal life support use in pregnancy is uncommon, and there are concerns related to an increased risk of maternal and fetal bleeding, hemolysis, and thrombotic complications associated with mechanical pump trauma and the use of systemic anticoagulation. Currently, there are no guidelines for ECLS use during pregnancy or postpartum, and there are limited reports in the literature describing the efficacy and safety of ECLS in this population. The vast majority of recent reports are related to ARDS due to influenza (H1N1).3 We describe our institutional experience with ECLS use in pregnant and postpartum women, and present a systematic review of the literature describing its use in this population. Methods We performed a series of computerized librarian-assisted searches using the databases PubMed and Embase (from January 2009 to February 2014). The search strategy was intended to include reports describing modern use of ECLS during the last 5 years. We restricted the results to articles published in English language. The PubMed searches were performed using the following Medical Subject Heading terms: 1) Pregnancy AND ARDS; 2) Pregnancy AND (extracorporeal oxygenation OR extracorporeal assist); 3) Post-Partum AND (extracorporeal oxygenation OR extracorporeal assist). The search strategy yielded 128 results in total. We then manually selected only reports that included the use of ECLS/ECMO during pregnancy or postpartum, and this search yielded 31 reports accounting for a total of 67 patients supported with this technology.
Key Words: extracorporeal membrane oxygenation, pregnancy, acute respiratory distress syndrome, postpartum, postpartum cardiomyopathy
Extracorporeal life support (ECLS) refers to the use of extra-
corporeal cardiopulmonary bypass in patients with cardiac or respiratory failure. The term extracorporeal membrane oxygenation (ECMO) is preferred for patients who only require respiratory support, although both terms are sometimes used interchangeably.1 ECMO has been used as a rescue therapy in patients with respiratory failure, including those with refractory hypoxemia due to acute respiratory distress syndrome (ARDS). Extracorporeal life support is commonly employed in patients with circulatory arrest or significant cardiac dysfunction. Over the last 5 years, there has been a substantial increase in the use of ECMO and ECLS for patients with cardiorespiratory failure, associated with an improvement in patient outcomes.2 For the purpose of this article, we will be referring to all cases of ECLS or ECMO as ECLS.
Results/Data Section Our experience: Case Reports We describe four pregnant patients who presented with respiratory distress and subsequently developed cardiorespiratory failure requiring ECLS therapy. Median age of the patients at presentation was 26 years. Most common initial presenting symptoms in all patients were malaise, dyspnea, and cough. Two patients were pregnant when ECLS was initiated, and two were postpartum. Indications for ECLS and type of support are shown in Table 1. Before ECLS, patients had received mechanical ventilation (MV) for an average of 4 days. Mean PaO2/FiO2 ratio at ECLS initiation was 51 mmHg. A double lumen internal jugular catheter (DLC) was used for veno-venous (V-V) ECMO cannulation, whereas femoral cannulation was preferred for veno-arterial (V-A) ECMO support. Anticoagulation therapy with heparin was followed in all patients according to our program guidelines (Table 2). Activated clotting time (ACT), activated partial thromboplastin time (aPTT), and thromboelastography were maintained between 160 and 180 seconds, 50 and 80
From the *Division of Pulmonary, Critical Care, and Sleep Medicine, and the †Department of Cardiothoracic Surgery, University of Alabama, Birmingham, Alabama. Submitted for consideration April 2014; accepted for publication in revised form August 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Enrique Diaz-Guzman, Lung Transplant and Adult ECMO program, University of Alabama, AL 1102 Jefferson Tower, 625, 19th Street South, Birmingham, AL 35294-7410. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0000000000000154
110
6
ECLS, extracorporeal life support; ARDS, acute respiratory distress syndrome; STEMI, ST elevation myocardial infarction.
12 52 Alive Alive V-V Peripartum cardiomyopathy ARDS unknown likely influenza Postpartum (Day 2)
V-A Cardiogenic shock likely viral Pregnant (34 weeks)
V-V Influenza (A) ARDS Postpartum (Day 1)
111
seconds, and reaction time 2.5–3.0 × normal, respectively.4 Although none of the patients developed severe hemorrhage, we observed occurrences of mild-to-moderate bleeding in two patients requiring blood transfusions to maintain a hematocrit more than 28%. One patient had mild hemorrhage around the tracheostomy and DLC cannula sites, while another patient had moderate postpartum uterine hemorrhage which resolved without intervention. In addition, one patient had thrombosis of the oxygenator membrane that did not require circuit change. Vaginal delivery of the fetus on ECLS was performed in one case. The other pregnant patient continued her pregnancy without any complications. Extracorporeal life support referral was made early in the course of MV in three patients (average days to referral 3–4 days from initiation of MV), while one had a relatively delayed referral due to initial improvement on conventional MV (Day 10). Early tracheostomy was performed in three patients to help with reduction in use of sedation. Mean duration on ECMO was 5 days. All patients survived hospitalization and were discharged without significant morbidity. Fetal survival was 75%.
Day 2
6 16 Alive
Stillborn
50
Day 1
4 Day 2 24 Alive
Alive
54
Day 10 20 Alive
Minor bleeding: tracheostomy site, ECMO catheter site Minor bleeding: vaginal bleeding STEMI, vaginal bleeding, clot in circuit Minor bleeding: vaginal bleeding, tracheostomy site bleeding V-V Mycoplasma ARDS Pregnant (25 weeks)
Complications Etiology/Indication Pregnant/Postpartum
Alive
47
Day ECMO Initiated After MV PEEP (cm of water) at initiation of ECMO PaO2 (mmHg) at initiation of ECMO Fetal Outcome Maternal Outcome Circuit (V-A/V-V)
Table 1. Description of Pregnant and Postpartum Patients Supported with ECLS at our Center
5
MODERN USE OF ECLS IN PREGNANCY AND POSTPARTUM
Days on ECMO
Review of Literature We found 31 published reports over the last 5 years describing ECLS use during pregnancy and postpartum, with a total of 67 patients supported with this technology: 15 reports of V-V ECMO, 16 reports of V-A ECMO, and 1 report of a lung assist device5 (Table 3). Overall, maternal and fetal survival with ECLS, based on published reports, were 80% and 70%, respectively. A query of the extracorporeal life support organization (ELSO) database revealed no additional cases of ECMO use in pregnancy or postpartum, largely due to a lack of adequate coding in the database. Indications for ECLS use in the above cases included severe ARDS, postpartum cardiogenic shock, and amniotic fluid embolism (Table 3). In most studies, anticoagulation for ECLS in pregnant and postpartum patients was maintained at the lower therapeutic level and adjusted by serial monitoring of aPTT or ACT levels. However, there was no consensus on the optimal range for maintaining anticoagulation. ACT ranged from 140 to 220 seconds and APTT from 50 to 80 seconds in various studies.9,10,16–18,28,29 The most common site of bleeding reported was around the tracheostomy and ECMO cannula site. A few cases reported mild-to-moderate amounts of postpartum vaginal bleeding, with one reporting catastrophic postpartum hemorrhage.3,19 Blood transfusions and albumin were given in most reports to maintain optimal circuit flow and hematocrit above 30%. Delivery of the fetus while on ECLS was mostly deferred, but in one case the fetus was successfully delivered via cesarean section while the mother remained on ECLS.20 Arrhythmia ablation and heart valve repair were also performed successfully on ECLS in many cases.12–15,27 Patients with severe bleeding, including pulmonary hemorrhage and postpartum bleeding, were supported by ECLS with favorable outcomes, suggesting a good safety profile with current technology available.10 Discussion A recent report based on a national database described a significant increase in ECLS utilization and improved outcomes,
112 SHARMA et al. Table 2. Anticoagulation Monitoring for Pregnant Patients on ECMO at our Institution
ACT, activated clotting time.
with survival rates of 58% for respiratory and 40–49% for cardiac patients.2 Extracorporeal life support therapy in nonpregnant patients has been shown to be safe when used in carefully selected individuals.34 Extracorporeal life support may help prevent maternal or fetal hypoxemia in pregnant patients with
severe cardiac or respiratory failure, when conventional methods of support fail to provide adequate oxygen delivery. Our review of the literature shows that ECLS in pregnancy appears to be uncommon with only 67 patients reported during the last 5 years. These results suggest that ECLS remains underutilized
Table 3. Use of ECLS in Pregnancy and Postpartum – A Summary of the Cases Reported in the Literature
Reference
No of Patients
6–8
3
9
1 1 1
10 11
33% pregnant and 66% Postpartum Postpartum Pregnant Postpartum
27
1
Pregnant 75% pregnant and 25% postpartum 70% pregnant and 30% postpartum Postpartum
28
1
Postpartum
29,30
2
31,32
2
50% pregnant and 50% postpartum Postpartum
33
1 1
Pregnant Pregnant
5 12–15
3,16–26
21
1 4
Pregnancy Status (%)
48
Indication for ECLS Amniotic fluid embolism Atonic uterine bleeding Pulmonary hemorrhage-related arrest Cerebral venous thrombosis/ respiratory failure ARDS: due to all trans retinoic acid Persistent arrhythmia/ cardiogenic shock H1N1 ARDS Severe mitral regurgitation due to infective endocarditis Takasubo’s cardiomyopathy/ cardiogenic shock Pulmonary embolus/right ventricular failure Postpartum cardiomyopathy/ cardiogenic shock Staphylococcal ARDS Cardiac arrest/post-ACLS/CPR
Survival
Mode of ECLS (V-A/V-V)
Maternal (%)
Fetal (%)
2 V-A and 1 V-V
100
100
100 100 100
100 0 100
100 100
0 50
92
74
V-A
100
100
V-A
100
100
V-A
100
100
V-A
100
50
V-V V-A
100 100
Unknown 0
V-A V-V V-V Lung assist V-A 3 V-A and 45 V-V
CPR, Cardio-pulmonary resuscitation; ECLS, extracorporeal life support; ARDS, acute respiratory distress syndrome; V-A, veno-arterial; V-V, veno-venous.
MODERN USE OF ECLS IN PREGNANCY AND POSTPARTUM
in pregnancy possibly due to concerns of increased bleeding in the mother and fetus.3,35 Nevertheless, we found only a few case reports of catastrophic bleeding, with overall maternal survival of pregnant and postpartum patients supported with ECLS similar to nonpregnant patients. At our institution, we routinely use ECLS to support patients with severe cardiopulmonary failure who fail to respond to conventional therapy. Most common indications include ARDS, severe pneumonia, status asthmaticus, pulmonary embolism, and cardiogenic shock. Pregnancy is not considered a contraindication for ECLS at our center. Pregnant patients are considered candidates if they have evidence of severe cardiopulmonary failure (PaO2/FiO2 ratio less than 100 mmHg after optimal positive end-expiratory pressure (PEEP) titration or cardiogenic shock compromising maternal and fetal survival). In case of hemorrhagic complications or evidence of fetal distress on ECLS, a cesarean section or vaginal delivery is offered to these patients. In addition, the obstetrical team performs intrauterine balloon tamponade for postpartum hemorrhage if indicated (none of our patients required this treatment). Moreover, we consider ECLS therapy in these patients if there is evidence of maternal or fetal viability and no major contraindications are present, such as severe uncorrectable coagulopathy (i.e., disseminated intravascular coagulation) and severe or uncontrollable active hemorrhage (i.e., uterine, gastrointestinal hemorrhage, etc.). Although none of our patients underwent cesarean section while receiving ECLS, reports in the literature suggest that the operation can be performed safely after a temporary suspension of anticoagulation.20,36 In addition, ECLS has been described in pregnant patients with severe pre-eclampsia, eclampsia, H- hemolysis, EL- elevated liver enzymes, LP- low platelets counts (HELLP) syndrome, and catastrophic antiphospholipid syndrome, although these pose a unique challenge as patients may have an increased risk for bleeding and thrombotic complications associated with refractory thrombocytopenia or hypercoagulable state.6,37,38 Finally, ECLS specialists should be aware of the possibility of amniotic fluid embolism in postpartum patients requiring ECLS, as this complication may be associated with a high rate of coagulopathy and bleeding, requiring continuous adjustment to anticoagulation parameters, transfusions, and hemorrhage control.6,39 Based on our limited experience and review of the available literature, we believe that ECLS can be used safely in well-selected pregnant and postpartum patients with severe cardiorespiratory compromise. We recommend early consultation with an ECLS center for pregnant patients with severe cardiorespiratory compromise to improve the chance of maternal and fetal survival. Our report is not without limitations. The number of cases that we reviewed only represents experience with ECLS over the last 5 years, and so it is possible that results may be different when analyzing ECLS use over previous decades. In addition, it is possible that we missed some cases that were not identified by our search engine. Finally, overestimation of survival with ECLS is possible due to publication bias from reporting only positive outcomes in the literature. We believe that additional information related to pregnant patients should be included in a national registry such as the ELSO database. This may provide a better understanding of the use and safety of ECLS in pregnant and postpartum women.
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