PRIMARY pulmonary hypertension (PPH) is a progressive and fatal disease characterized by elevation of the pulmonary vascular resistance and right heart failure. 1,2PPH often becomes evident during pregnancy and may lead to maternal death during pregnancy, labor, or in the postpartum period. We describe a case of a pregnant woman with severe PPH and heart failure who underwent Cesarean section for termination of pregnancy under general anesthesia with the assistance of extracorporeal membrane oxygenation (ECMO).
A 33-yr-old primigravida woman (147 cm, 39.5 kg, body surface area 1.28 m2) was transferred at 18 weeks gestation for evaluation of heart failure. Her sister had died suddenly of unknown causes at 5 yr of age. The patient had been asymptomatic over the preceding few years except for shortness of breath on exertion. She had experienced increasing shortness of breath over several weeks and on the day of admission was dyspneic at rest.
A 12-lead electrocardiograph demonstrated a sinus tachycardia (104 beats/min) with right axis deviation and incomplete right bundle branch block. Transthoracic echocardiography demonstrated right ventricular dilatation with compression of the ventricular septum toward the left ventricle. Defects of the atrial and ventricular septum were not detected. A pulmonary artery and radial artery catheter were inserted under local anesthesia. The hemodynamic parameters obtained on the day of hospital admission are presented in table 1. The respiratory rate was 28 breaths/min. Blood tests revealed a white blood cell count 12,300/μl, hemoglobin 12.6 g/dl and platelet count 6.6 × 104/μl while arterial blood gases on room air were pH 7.395, Paco228.4 mmHg, Pao285.8 mmHg and base excess −6.4 mm. Pulmonary arteriography excluded a pulmonary embolism. On the basis of these data, a clinical diagnosis of PPH was made. The patient was treated with heparin 10,000 U/day, nitroglycerin 0.5 μg · kg−1· min−1, and antithrombin III 1,500 unit by intravenous administration.
The patient developed worsening dyspnea on the second day after admission. The pulmonary artery pressure (PAP) further increased to 100/60 mmHg (mean 74), exceeding the systemic arterial pressure (SAP) of 98/64 mmHg (mean 77); the ratio of mean PAP to mean SAP (Pp/Ps) increased from 0.52 to 0.96. The platelet count decreased to 5 × 104/μl. It was decided that interruption of pregnancy was in the best interest of the patient. The obstetricians judged that a vaginal evacuation at 18 weeks gestation was inappropriate in view of the immaturity of the uterine cervix and the anticoagulant therapy. Therefore, a Cesarean section was planned under general anesthesia with the support of ECMO. ECMO was composed of a centrifugation pump and a pump controller (Capiox SP-101, Terumo Inc., Tokyo, Japan), a heparin-bonding ECMO circuit (Capiox-SX EBS cardiopulmonary kit, Terumo Inc.), and heparin-bonding cannulae (Capiox percutaneous catheter, Terumo Inc). After a small incision to expose the femoral artery and vein under local anesthesia, a 21-French draining can-nula was inserted into the right atria through the femoral vein and a 17-French perfusion cannula was inserted through the femoral artery, in the fluoroscopy room. ECMO was started at a flow rate of 1.5 l · min−1· m−2.
In the operating room, general anesthesia was induced with midazolam (2 mg), fentanyl (200 μg), and vecuronium (10 mg) allowing tracheal intubation. Anesthesia was maintained with intravenous fentanyl (200 μg/h) and propofol (100 mg/h). The patient was on mechanical ventilation with oxygen and air (Fio2= 0.4). ECMO flow was maintained between 2.5–4.0 l/min throughout the anesthesia. SAP and cardiac output (CO), which was measured by continuous thermodilution (Vigilance, Continuous cardiac output monitor, Edwards Lifesciences, Irvine, CA), were essentially unchanged following induction and tracheal intubation. The PAP gradually decreased while the SAP was unchanged through the general anesthesia. The operation was performed uneventfully with 470 g of blood loss. The activated clotting time (ACT) was 150 s and 144 s at the start and the end of anesthesia respectively.
The patient was admitted to the intensive care unit for postoperative management and was extubated 4 h after the end of the anesthesia. We were unable to wean the patient from ECMO by simply lowering the flow rate, because lowering of the ECMO flow rate resulted in an increase in the PAP and cardiac index (CI) and a fall in the SAP (fig. 1). On the forth postoperative day (POD), nitric oxide inhalation was commenced through a semiclosed circuit with a tight fitting facemask. In addition, an epoprostenol (prostacyclin) infusion was commenced via the pulmonary artery catheter, and was continued at a dose of 4.5–6.5 ng · kg−1· min−1throughout the patient's stay in the intensive care unit. PAP was 93/36 mmHg (mean 56), 96/36 mmHg (mean 57), and 95/19 mmHg (mean 45) before, during 10 parts per million, and 20 parts per million of nitric oxide inhalation, respectively, while ECMO flow was set at 1.2 l · min−1· m−2. Nitric oxide inhalation was discontinued on the sixth POD, as it was ineffective.
The ECMO flow rate was slowly tapered and the ECMO circuit required changing on the ninth, thirteenth, and seventeenth POD as a result of degradation and coagulation of the artificial lung. When the flow rate was decreased to 0.3 l/m2on the eighteenth POD, the PAP was 89/22 mmHg (mean 45), SAP was 105/55 mmHg (mean 72), and the Pp/Ps ratio was 0.63, which was comparable to the value on the forth POD. Although lung transplantation was considered as an alternate therapeutic strategy, there was no suitable brain-dead or live related donor available. The patient died of right heart failure 7 h after the withdrawal of ECMO on the nineteenth POD. An autopsy revealed pathologic evidence of PPH with medial thickening and narrowing of the lumina of the pulmonary arteries.
PPH is a very rare disease, but the onset of PPH is most common in young to middle-aged women. 1,2Pregnancy often precedes the development of symptoms of PPH. Indeed, the mortality rate of pregnant patients with PPH is very high, at about 30%. 3During the first, second, and third trimesters the total blood volume increases above the prepregnant level by 10%, 30%, and 45% respectively. 4This is associated with an increase in the end diastolic volume and heart rate while CO increases by 50% by the second trimester during a normal pregnancy. 5Pregnant women with PPH tolerate this hemodynamic stress very poorly and may therefore develop heart failure during pregnancy, particularly in the second and third trimester. 6Moreover, the vast majority of patients with PPH die in the postpartum period, because venous return is suddenly increased as the blood volume retained in the dilated veins of the gravid uterus returns to circulation by uterine contraction. 7PPH patients, classified in the New York Heart Association (NYHA) function classes I and II, exhibit a significant fall in pulmonary vascular resistance with nitric oxide, epoprostenol, or adenosine, and can be managed by the use of these drugs or calcium-channel blockers. 2However, severe PPH, classified in NYHA function classes III and IV, are treated by epoprostenol administration or lung transplantation. 2,8,9
The optimal method to anesthetize patients with PPH for Cesarean section is controversial but depends on the severity of the disease in individual cases. 10Most previous reports describing successful management of such patients utilized epidural anesthesia. 11–16All PPH patients described in these reports exhibited a normal CO in the preoperative period and lowering of the PAP following the administration of vasodilators or nitric oxide inhalation. 11–16General anesthesia is also of potential use for PPH patients, 17but does have significant disadvantages, such as increased pulmonary vascular resistance by positive pressure ventilation or nitrous oxide inhalation, 18and reduced cardiac contractility by volatile anesthetic agents. Since the patient in this report exhibited a low CO and was classified in NYHA IV in the preoperative period, we used ECMO for the perioperative cardiopulmonary management.
ECMO by means of peripheral cannulation is also called percutaneous cardiopulmonary support, and is an established therapeutic strategy in adult patients with cardiopulmonary failure. ECMO is mostly used for cardiac support and is rarely used for respiratory distress. ECMO involves partial cardiopulmonary support and should be applied for a short duration. Therefore ECMO is most appropriate for the patient whose cardiopulmonary function is expected to recover within a few days. Acute pulmonary embolism accompanied by pulmonary hypertension and right heart failure is a suitable indication for ECMO, 19,20because the heart failure and pulmonary hypertension may be ameliorated following surgical embolectomy. Although all components of ECMO were heparin-bonded, use of an anticoagulant drug is recommended so that ACT is kept over 150 s. Heparin-bonded components of ECMO would be advantageous for minimizing operative bleeding by administrating none or the least dose of anticoagulant drugs.
There are few reports about the application of ECMO during general anesthesia for patients with pulmonary hypertension. In an earlier report of a patient with chronic pulmonary hypertension, ECMO was successfully applied to a patient scheduled to undergo Cesarean section using general anesthesia. 21Previous reports describe the use of ECMO in the successful recovery of a patient with severe PPH following a cardiac arrest during the induction of anesthesia for lung transplantation. 22,23Since the pulmonary vascular resistance of patients with severe PPH might be fixed or progressively increase, we were unable to wean our patient off ECMO after the termination of the pregnancy despite the administration of nitroglycerin and epoprostenol and nitric oxide inhalation. 24 14 16
Although no conclusion can be drawn from this case, we suggest that ECMO should be considered for the perioperative management of patients with severe PPH to prevent circulatory failure or as a bridging therapy prior to lung transplantation.