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Anesth Analg 2004;98:822-824 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000099717.40471.83
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Abstract |
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This case represents the first reported use of levosimendan, a calcium-sensitizing drug with additional vasodilation properties, for treatment of a woman with peripartum cardiomyopathy. Levosimendan induced a steady decline of increased pulmonary capillary wedge pressure, followed by a definitive increase in cardiac stroke volume. The patient recovered from this serious episode of heart failure, and she ultimately regained left ventricular function.
IMPLICATIONS: Acute heart failure is a life-threatening event that only rarely occurs during childbirth. We report a case of a woman who experienced cardiovascular collapse during vaginal delivery. We determined that she met current diagnostic criteria for peripartum cardiomyopathy, and we successfully treated her with levosimendan, a calcium-sensitizing drug with additional vasodilation properties.
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Introduction |
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TopAbstractIntroductionCase ReportDiscussionConclusionReferences |
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Peripartum cardiomyopathy (PPCM) is an unusual and uncommon cause of antepartum and postpartum heart failure. Current diagnostic criteria include 1) onset of heart failure in the last month of pregnancy or within 5 mo postpartum, 2) absence of an identifiable cause of cardiac failure, 3) absence of recognizable heart disease before the last month of pregnancy, and 4) echocardiographic evidence of left ventricular systolic dysfunction, including left ventricular ejection fraction (LVEF) <45%, and/or decreased fractional shortening <30%, and/or left ventricular end diastolic dimension (LVEDD) >2.7 cm/m2 (1–3). We report a case of a woman with PPCM presenting at vaginal delivery; she was successfully treated with levosimendan, a new calcium sensitizer with additional vasodilation properties (4–6).
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Case Report |
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A 22-yr-old woman, primipara and primigravida at week 39 of gestation, was admitted to the hospital with spontaneous labor. Spinal anesthesia was administered for pain relief after hydration with 1 L of Ringer’s lactate solution over 1 h. Preanesthesia vital signs were normal; maternal blood pressure was 135/70 mm Hg, maternal heart rate was 95 bpm (bpm), and fetal heart rate was 140–150 bpm. A spinal needle (24-gauge) was placed in the subarachnoid space at the L3-4 interspace, and 2.5 mg of bupivacaine (0.25%, isobaric) and 5 µg of sufentanil (in a total volume of 1.1 mL) were injected over a 10-s interval. Within 5 min, a sensory block was effective at the T7-8 dermatome. The mother was awake and alert, and her hemodynamic state was stable, with blood pressure 120/70 mm Hg and heart rate of 100 bpm. However, within 10 min after initiation of anesthesia, the fetal heart rate decreased sharply to 50 bpm. Oxygen was administered at 6 L/min by face mask and the mother was positioned for a forceps delivery.
During delivery, the patient suddenly became apneic and unresponsive. Despite IV administration of ephedrine (2 doses within 1 min; total 30 mg), her heart rate decreased to 45 bpm and her blood pressure decreased to a level too low to measure. Without a need for anesthesia, the patient was intubated and ventilated with 100% oxygen. A palpable, regular pulse was restored by IV epinephrine (2 doses; total 0.4 mg) followed by colloid solution (500 mL in 20 min). Blood pressure was 125/70 mm Hg, heart rate was 150 bpm, oxygen saturation (SpO2) was 100%, and end-tidal CO2 (ETCO2) was 23 mm Hg. Cardiovascular collapse of the mother lasted <3 min and the delivery was subsequently completed. The 2800-g newborn girl had an Apgar score of 0 at birth but was successfully resuscitated to Apgar 6 at 5 min and 8 at 10 min and was discharged from the neonatal intensive care unit (ICU) 2 d later.
After delivery, the patient was transferred to the ICU under continuous infusion of sufentanil (10 µg/h) and propofol (100 mg/h). Her systolic blood pressure was low (80 mm Hg), she experienced tachycardia (heart rate 155–165 bpm), and her chest radiograph showed evidence of pulmonary edema. Transthoracic echocardiography (TTE) showed LVEF <20%, LVEDD of 2.9 cm/m2, and a septal thickness of 7 mm. The patient’s cardiac troponin I level was also high (maximally elevated to 9.0 pg/mL at hour 4; normal level <0.4 pg/mL). Severe cardiogenic shock was diagnosed.
We inserted a pulmonary artery (PA) catheter and administered IV treatment, including a loop diuretic (furosemide), venous vasodilator (nitrates), and a ß-adrenergic agonist (dobutamine 10 µg · kg-1 ·min-1) for 24 h. Despite therapy, pulmonary capillary wedge pressure (PCWP) remained increased (18 mm Hg), LVEF did not improve, cardiac output (CO) and stroke volume (SV) remained low (5.6 L/min and 40 mL, respectively), and tachycardia persisted (heart rate, 140 bpm).
Because of the continuing dobutamine infusion, levosimendan was introduced as a small-dose loading infusion (3 µg/kg over 10 min), followed by a standard continuous infusion of 0.1 µg · kg-1 ·min-1 over 24 h. PCWP levels were decreased at the earliest measurements (1 h, 2 h), and normal values were reached (12 h after the start of levosimendan infusion) in a context of zero fluid balance (Fig. 1). SV and mixed venous oxygen saturation (SVO2) were also improved 10 h after levosimendan start-up (SV in Fig. 1; SvO2 increased from 62% to 74%). Based on these hemodynamic improvements, dobutamine therapy was discontinued. Two days after initiation of levosimendan (D2), TTE showed LVEF increased to 40%. On D3 the patient was tracheally extubated, the PA catheter was removed (PCWP, 3 mm Hg; CO, 9.0 L/min; SV, 87 mL), and treatment with the angiotensin-converting-enzyme-inhibitor captopril was started. The patient was discharged from the ICU on D4. By D9, LVEDD was less than 2.6 cm/m2, and LVEF was improved to 45%. After 10 wk, LVEF was further improved to >60%.
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With the patient’s consent, blood and milk samples were taken at D5 and D6 to determine levels of levosimendan and its active metabolite OR-1896 by high-performance liquid chromatography. Levosimendan was not detected in either the plasma or the milk, nor was OR-1896 detected in the plasma. However, measurable levels of OR-1896 were present in milk samples (0.10 and 0.08 ng/mL at D5 and D6, respectively).
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Discussion |
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TopAbstractIntroductionCase ReportDiscussionConclusionReferences |
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Peripartum cardiomyopathy occurs in fewer than one in 4000 pregnancies, but the outcome can be devastating; mortality rates range from 20% to 85% (3,7). Factors associated with increased risk for PPCM include advanced maternal age (>30 years), race (more black patients than others), multiparity, twin pregnancy, preeclampsia, and gestational hypertension (1,7). The condition has nevertheless been reported in young women, in primiparous women, and in white and Asian women (8). Little is known regarding the etiology of PPCM and specific therapy; therefore, medical treatment has been traditionally limited to drugs that control symptoms.
Our patient fulfilled clinical criteria for PPCM, including 1) acute onset of heart failure at delivery, 2) lack of evidence for preexisting heart disease or cause for sudden onset, and 3) echocardiographic support for left ventricular failure (LVEF, <20%; LVEDD, 2.9 cm/m2) (1). Her rapid cardiovascular decline could have resulted, in part, from abrupt changes in ventricular loading after initiation of spinal anesthesia, as previously described (9). Increased ventricular work during delivery likely contributed to the acute heart failure as well. The persistence of ventricular dysfunction at 10 days postpartum was also consistent with a diagnosis of PPCM. Myocardial injury in our patient (troponin I level of 9 pg/mL) probably resulted from an imbalanced supply/demand for oxygen in the myocardium; low blood pressure (80 mm Hg) likely lessened the oxygen supply, whereas tachycardia (heart rate, 165 bpm) and use of dobutamine increased the oxygen demand. Indeed, one cannot exclude that troponin I release may be facilitated in patients with PPCM.
Alternative explanations for cardiovascular collapse—such as anesthesia-associated respiratory arrest, (10) anaphylactic shock, or amniotic fluid embolism (11)—were possible but not fully consistent with this patient’s overall clinical condition during and after childbirth. In her case, respiratory arrest as a direct result of anesthesia was improbable because the anesthesiologist did not note signs of respiratory depression before cardiovascular collapse. Anaphylactic shock was also unlikely because the patient received no drugs known to induce such reactions and the patient lacked bronchospasm or cutaneous signs. Amniotic fluid embolism—a rare complication presenting with hemodynamic collapse, hypoxia, seizure, and coagulopathy—was possible but doubtful because of the clinical course and because our patient had no evidence of coagulopathy (11).
As dobutamine treatment (24 h) failed to improve hemodynamic variables and may have been associated with myocardial injury in our patient, we opted for therapy with levosimendan, a new drug for treating acute heart failure. Levosimendan enhances cardiac contractility by improving the response of cardiac myofilaments to intracellular calcium, and it reduces cardiac workload by opening adenosine triphosphate-dependent potassium channels for dilation of blood vessels (12). Because levosimendan does not increase intracellular calcium levels, it is less likely than traditional inotropes (ß-agonist inotropes or phosphodiesterase inhibitors) to have deleterious effects on cardiac myocyte relaxation, cell survival, and arrhythmia induction (13). As described in other studies of patients with severe low-output heart failure, our patient responded favorably to levosimendan therapy with increased SV and decreased PCWP (5,6).
Certain special considerations are important for women who just delivered and are treated for acute heart failure of PPCM. Our case showed that hemodynamic improvements persisted after levosimendan infusion ended, and these prolonged effects were likely attributable to production of an active metabolite with a long half-life (OR-1896, t1/2 = 80 h) (14). Because we detected OR-1896 in human milk, additional studies are needed to determine the duration of a recovery period during which levosimendan-treated mothers should avoid breast-feeding. Furthermore, although our PPCM patient regained normal LV function in 10 weeks, it remains unclear whether recovered patients can experience subsequent pregnancy without recurrent cardiomyopathy (1). We therefore advised our patient of potential risks and counseled her to seek care at a high-risk perinatal center if she should become pregnant again.
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Conclusion |
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TopAbstractIntroductionCase ReportDiscussionConclusionReferences |
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Anesthesiologists should be aware of PPCM, an uncommon but life-threatening condition. This case represents the first reported use of levosimendan for treatment of a woman with PPCM who experienced acute heart failure during childbirth. When treated with levosimendan shortly after the birth of her daughter, the mother showed a steady decline of increased PCWP, followed by a definitive increase in cardiac SV. She recovered from this serious episode of heart failure, and she ultimately regained normal LV function.
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Acknowledgments |
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Supported, in part, by a grant (EA 322) from the Ministère de l’Enseignement et de la Recherche.
The authors would like to thank Drs. J. Matéo, E. Renaud, P. Henry, S. Cosson, J. Oliary, Mrs. Faivre, and the ICU nursing staff for help in managing this patient and Jukka Herttuainen (Orion Pharma, Finland) that performed HPLC for levosimendan and OR-1896 measurements.
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References |
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- Beus E, Mook W, Ramsay G, et al. Peripartum cardiomyopathy: a condition intensivists should be aware of. Intensive Care Med 2003; 29: 167–74.[Medline]
- Gilles A, Antoine M, Vincent J, Kleeman U. Peripartum cardiomyopathy. Rev Med Brux 2001; 22: 436–8.[Medline]
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- Moiseyev V, Poder P, Andrejevs N, et al. Safety and efficacy of a novel calcium sensitiser, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction (a randomised, placebo-controlled, double-blind study; RUSSLAN). Eur Heart J 2002; 23: 1422–32.
[Abstract/Free Full Text] - Follath F, Cleland J, Just H, et al. Efficacy and safety of intravenous levosimendan, a novel calcium sensitiser, in severe low output failure (the LIDO study): a randomised double-blind trial. Lancet 2002; 360: 196–202.[Web of Science][Medline]
- Slawsky MT, Colucci WS, Gottlieb SS. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 2000; 102: 2222–7.
[Abstract/Free Full Text] - Pearson G, Veille J, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (NIH) workshop recommendations and review. JAMA 2000; 283: 1183–88.
[Abstract/Free Full Text] - Lampert M, Lang R. Peripartum cardiomyopathy. Am Heart J 1995; 130: 860–70.[Web of Science][Medline]
- Malinow A, Butterworth J, Johnson M, et al. Peripartum cardiomyopathy presenting at Cesarean delivery. Anesthesiology 1985; 63: 545–7.[Medline]
- Lu J, Manullang T, Staples M, et al. Maternal respiratory arrests, severe hypotension, and fetal distress after administration of intrathecal sufentanil and bupivacaine after intravenous fentanyl. Anesthesiology 1997; 87: 170–2.[Web of Science][Medline]
- Davies S. Amniotic fluid embolus: a review of the literature. Can J Anaesth 2001; 48: 88–98.[Web of Science][Medline]
- Lehtonen L. Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory properties. Expert Opin Investig Drugs 2001; 10: 955–70.[Medline]
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- Kivikko M, Antila S, Eha J, et al. Pharmacodynamics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Pharmacol Ther 2002; 40: 465–71.
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