Eclampsia as a cause of secondary non-obstructive central sleep hypoventilation

Eklampsie jako příčina sekundární neobstrukční centrální spánkové hypoventilace

Centrální alveolární hypoventilace charakteru Ondininy kletby je onemocnění spojené s chybějící či zhoršenou ventilační odpovědí na hyperkapniia/či hypoxii se současným poklesem saturace až k 50 %. Sekundární formy mohou často vzniknout v rámci inzultu postihujícího mozkový kmen. V prezentované kazuistice předkládáme případ 24leté provorodičky ve 41. týdnu těhotenství s nekomplikovaným průběhem, u které vznikla po eklamptickém záchvatu sekundární neobstrukční spánková hypoventilace.

Prezentované sdělení přináší podporu pro použití domácího BiPAP (Biphasic Positive Airway Pressure) u pacientů se sekundární Ondininou kletbou.

Klíčová slova:
eklampsie, sekundární Ondinina kletba, BiPAP, centrální neobstrukční spánková hypoventilace

Authors: P. Štourač 1;  T. Hradilová 1;  E. Straževská 1;  P. Turčáni 2;  A. Štouračová 3;  P. Janků 4;  J. Skřičková 2;  R. Gál 1
Authors place of work: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Brno Medical Faculty of Masaryk University, Brno, head of the department prof. MUDr. R. Gál, Ph. D. 1;  Department of Pulmonary Diseases and Tuberculosis, University Hospital Brno Medical Faculty of Masaryk University, Brno, head of the department prof. MUDr. J. Skřičková, CSc. 2;  Department of Radiology, University Hospital Brno, Medical Faculty of Masaryk University, Brno head of the department prof. MUDr. V. Válek, CSc., MBA 3;  Department of Obstetrics and Gynecology, University Hospital Brno, Medical Faculty of Masaryk University, Brno, head of the department prof. MUDr. P. Ventruba, DrSc., MBA 4
Published in the journal: Ceska Gynekol 2015; 80(1): 16-19


The central alveolar hypoventilation of Ondine´s curse is a disorder characterized by absent or diminished ventilatory response to hypercapnia, hypoxia or both, with parallel decrease in saturation to 50%. The secondary form may begin mainly after insult that affects the brain stem. We present a case of a 24-years old primipara in the 41st gestational week with an uncomplicated course of pregnancy and with secondary non-obstructive sleeping hypoventilation which occurred after eclamptic seizure.

This obstetric case provides evidence for the benefit of home BiPAP use for patients with secondary Ondine‘s curse.

eclampsia, secondary Ondine´s curse, Biphasic Positive Airway Pressure, central non-obstructive sleeping hypoventilation


Central alveolar hypoventilation of Ondine′s curse is a disorder characterized by absent or diminished ventilatory response to hypercapnia, hypoxia or both, with parallel decrease in saturation to 50% or less for 10 seconds or more [12]. The lungs are normal and there is no demonstrable abnormality of the central nervous system [14]. The congenital form is very rare and it is most often caused by mutations in the paired-like homeobox 2B (PHOX2B) gene typically associated with Hirschprung disease [8]. The secondary form may begin mainly after infection, cerebrovascular ischemia, surgical operation, general anaesthesia, drug intake, multiple sclerosis, Chiari malformation or cancer that affects the brain stem [3, 9–11]. The condition can be effectively treated with assisted ventilation during sleep. The term Ondine´s curse was first used for primary alveolar hypoventilation in 1962 by Severinghaus and Mitchell and remains a rare disease [13].

Preeclampsia is characterized by high blood pressure and significant proteinuria after the 20th week of pregnancy. If left untreated, it can develop into eclampsia. Early diagnosis of hypertension and subsequent antihypertensive medication administration is the right clinical approach to prevent eclampsia, the most severe complication of preeclampsia [15].

We present a case of a parturient with a secondary non-obstructive hypoventilation that occurred after an eclamptic seizure.


A 24-years old primipara in the 41st gestational week with a history of viral pneumonia and myocarditis on artificial ventilation in 1993, recurrent infections of the respiratory tract, without any regular medication or care. The course of pregnancy was uncomplicated with regular prenatal care. She was found unconscious at home by her mother who did not see convulsions. She complained of severe headaches and failure of short-term memory on arrival of the Emergency Medical Service (EMS). She was transferred to the maternity ward of the University hospital. Another eclamptic seizure occurred with unconsciousness, desaturation (SpO2 86 %), hypertension (144/105 mm Hg to 220/150 mm Hg; monitored per three minutes), tachycardia (95 per minute), cyanosis and convulsions during the length patient‘s admission. Diazepam 10 mg IV and magnesium sulphate 4 g IV were administered and the convulsions stopped but hypoventilation increased. GCS was 8 and the patient was immediately intubated by anaesthesiologist without the use of muscle relaxation and antihypertensive therapy was started with urapidil 12.5–25 mg IV in boluses. The obstetrician indicated emergent Caesarean delivery due to fetal hypoxia. General anaesthesia was induced with thiopentone 5 IV, maintained with sevoflurane 1.0 MAC and N2O 50%, blood pressure improved (130/80 mm Hg). After cutting the umbilical cord, sufentanile 15 µg IV, cis-atracurium 6 mg IV and oxytocine 5 mg IV were administered.

The newborn was a girl weighing 2800 g, 41 cm in length, heart rate 140 per minute with Apgar scores 1-5-7, pH 7.00, pauO2 3.5 kPa, pauCO2 13.9 kPa, BE -9.0 mmol.L-1 and full subsequent postnatal adaptation. Blood loss was 500 mL. The patient was artificialy ventilated and transferred under continuous sedation to the Intensive Care Unit. Brain Computer Tomography (CT), ECG, Doppler echocardiography and chest X-ray were performed during the first 24 hours postoperatively with no pathological findings. She was then awakened and extubated with no signs of respiratory depression.

After extubation, repeated short episodes of insignificant hypoventilation with decrease in oxygen saturation (85–90%) occurred. We treated this with respiratory stimulants (aminophylline 480 mg IV continuously per day, methylphenidate 10 mg PO each 12 hours) and antidotes to administered drugs (physostigmine 2 mg IV, naloxone 0.1 mg IV in case of hypoventilation). Magnesium sulphate 2 g per hour IV continuously was administered as a prevention of seizures. We continued antihypertensive therapy with urapidil 10–40 mg.hour-1 and then due to abnormal values of blood pressure we switched to dihydralazine 1–2 mg.hour-1 with sufficient clinical effect. We noted only high levels of uric acid in serum (545 µmol/L-1) and the presence of protein and uric acid in urine from laboratory findings. The other laboratory tests (acid base balance, hematology, biochemistry, urinary) showed no pathological changes.

On the second postoperative day during the night, severe hypoventilation with desaturation (SpO2<85%) and sopor occurred abruptly with subsequent intubation and sedation. There was severe respiratory acidosis in blood gases (pH 7.05, PaCO2 18.2 kPa, PaO2 14.8 kPa, HCO3 36.1 mEq.L-1, BE -0.7).

Brain Magnetic Resonance Imaging (MRI) and CT of the patient‘s brain showed no significant pathology. The cerebrospinal fluid (CSF) sample was negative for multiple sclerosis and inflammation signs. Uric acid in serum decreased to 385 µmol.L-1.

There were still episodes of hypoventilation with desaturation even on small doses of sedation with intravenous sufentanil 5 µg.hour-1 for orotracheal tube tolerance. Based on negative brain imaging, we decided to stop sedation and extubated her again on the fifth postoperative day.

We then performed electroencephalography (EEG), showing frontal lobe intermittent rhythmic delta activity (FIRDA) waves, typical for brainstem post-ischemic changes. We indicated Biphasic Positive Airway Pressure (BiPAP) application for sleep due to repeated episodes of enhanced hypoventilation and desaturation during sleep.

The patient accepted BiPAP (Respironics, Philips, Netherlands) treatment at night. BiPAP was set initially to inspiration support (IPAP) 7 cm H2O, expiration pressure (EPAP) 3 cm H2O. Night blood gas sample showed no abnormalities(pH 7.44, PaCO2 5.4 kPa, PaO2 12.5 kPa, HCO3 27.0 mEq.L-1, BE 2.6, SaO2 97%).

On the 16th postoperative day, she was transferred to the Department of Pulmonary Diseases, where central sleep hypoventilation was confirmed during examination in sleep (chest and abdomen wall movement, snoring, pulse rate, blood pressure, ECG, SpO2, breath rate). There was SpO2 < 85% for 34% for the sleeping period and maximal desaturation value was SpO2 17%.

On the 32nd postoperative day, the patient was discharged to home care with a BiPAP device for night use. At present, she is in permanent pulmonary dispensary and still uses the BiPAP (IPAP 12 cm H2O, EPAP 3 cm H2O) at night. She is able to care for the child without any limitations.


Secondary nonobstructive central sleep hypoventilation of Ondine´s curse due to eclampsia has not often been published and is a very rare syndrome.

The management of this case was divided into several parts. First was the management of the preeclampsia. There was no history of hypertension, proteinuria or high uric acid levels in serum during regular prenatal examination. For this reason, when all the parameters described were positive on admission, preeclampsia with subsequent eclampsia seemed to be the right diagnosis [4]. Early diagnosis of preeclampsia and antihypertensive therapy is reported as a prevention of eclampsia [15]. We started antihypertensive therapy with urapidil and successfully changed to dihydralazine due to inadequate effect. Wacker et al. reported no advantage of dihydralazine to urapidil in the treatment of severe preeclampsia but we favoured dihydralazine [16]. The important aspect was the eclampsia treatment and prevention of another eclamptic seizure. The diazepam and magnesium sulphate were administered in accordance with published recommendations [1].

Another important aspect was the fetus rescue. Two approaches to the management of the fetus were considered; emergent versus elective Caesarean Section (CS). We decided on emergent CS due to ongoing fetal hypoxia. Alternative management is based on effective treatment and prevention of seizures and subsequent vaginal or Caesarean delivery [4].

The last aspect to be considered was postoperative care. We decided to examine the patient under sedation due to the risk of intracranial pathology. This was excluded. She was awakaned and extubated, but periods of repeated hypoventilation remained. In the immediate postoperative period, we tried to exclude any abnormal response or any residual effect of different anaesthetic drugs that had been administered. The initial but temporary response to naloxone could be attributed to its central analeptic effect [5]. Unfortunately, we only had laboratory values of blood gases avail-able. Continuous feedback on pCO2 values could help confirm the diagnose earlier, avoiding severe hypoventilation during sleep and intubating her again. Another brain CT and brain MRI were performed without confirmation of intracranial pathology. Multiple sclerosis signs were also negative both on brain MRI and in the CSF. In the end we inclined to a diagnosis of brain stem ischemia due to eclampsia based on EEG changes and started noninvasive support ventilation of the patient during the night. Oxygen is not considered as an effective treatment, since it will only reduce the fall of SpO2, but not modify hypercapnia [2]. Sleep laboratory examination (without BiPAP) showed long period of desaturation and confirmed the need for permanent use of ventilator support during the night [7]. Electrophrenic pacing was not used as it may have led to upper airway occlusion [6].

The woman in this case was asymptomatic until she was exposed to eclampsia. To confirm a diagnosis of congenital Ondine‘s syndrome, detecting a mutation in the PHOX2B gene is required but this was not available in the Czech Republic at that time. On the other hand, the patient had been exposed to sedation during mechanical ventilation without the syndrome appearance in 1993. Hence the congenital form is unlikely [10].


This obstetric case provides evidence for the benefit of home BiPAP use for patients with secondary Ondine‘s curse.


The authors gratefully acknowledge financial support from the Czech Ministry of Health Internal Grant Agency - project No. NT 13906-4/2012.

korespondující autorka

Tereza Hradilova, MD

Department of Anaesthesiology and Intensive Care Medicine

Faculty of Medicine Masaryk University

University Hospital Brno

Jihlavska 20

625 00 Brno

Czech Republic



1. Altman, D., Carroli, G., Duley, L., et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet, 2002, 359(9321), p. 1877–1890.

2. Bubis, M., Athonissen, N. Primary alveolar hypoventilation treated by nocturnal administration of O2. Am Rev Respir Dis, 1978, 118, p. 947–953.

3. Butin, M., Labbé, G., Vrielynck, S., et al. Late onset Ondine syndrome: literature review on a case report. Arch Pediatr, 2012, 19, 11, p. 1205–1207.

4. Dennis, A. Management of pre-eclampsia: issues for anaesthetists. Anaesthesia, 2012, 67, 9, p. 1009–1020.

5. Golder, F., Hewitt, M., McLeod, J. Respiratory stimulant drugs in the post-operative setting. Respir Physiol Neurobiol, 2013, 189, 2, p. 395–402.

6. Hyland, R., Hutcheon, M., Perl, A., et al. Upper airway occlusion induced by diaphragm pacing for primary alveolar hypoventilation: implications for the pathogenesis of obstructive sleep apnoea. Am Rev Respir Dis, 1981, 124, p. 180–185.

7. King, T. Restrictive lung disease in pregnancy. In: Nieder-man, M., ed. Clinics in Chest Medicine. Philadelphia, Saunders, 1992, 13, p. 607–622.

8. Kwon, M., Lee, G., Lee, M., et al. PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature. Eur J Pediatr, 2011, 170, p. 1267–1271.

9. Levitt, P., Cohn, M. Sleep apnea and the Chiari malformation: case report. Neurosurgery, 1988, 23, p. 508.

10. Mahfouz, A., Rashid, M., Khan, M., et al. Late onset congenital central hypoventilation syndrome after exposure to general anesthesia. Can J Anaesth, 2011, 58, 12, p. 1105–1109.

11. Ochoa-Sepulveda, J., Ochoa-Amor, J. Ondine‘s curse during pregnancy. J Neurol Neurosurg Psychiatry, 2005, 76, 2, p. 294.

12. Pieters, T., Amy, J., Burrini, D., et al. Normal pregnancy in primary alveolar hypoventilation treated with nocturnal nasal intermittent positive pressure ventilation. Eur Respir J, 1995, 8, p. 1424–1427.

13. Severinghaus, J., Mitchell, R. Ondine´s curse: failure of respiratory center automaticity while awake. Clin Res, 1962, 10, p. 122. [abstract]

14. Shneerson, J. Disorders of autonomic control of respiration. In: Shneerson, J., ed. Disorders of Ventilation. Oxford, Blackwell Scientific Publications, 1988, p. 118–127.

15. Too, G., Hill, J. Hypertensive crisis during pregnancy and post-partum period. Semin Perinatol, 2013, 37, 4, p. 280–287.

16. Wacker, J., Wagner, B., Briese, V., et al. Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil. Eur J Obstet Gynecol Reprod Biol, 2006, 127, 2, p. 160–165.

Dětská gynekologie Gynekologie a porodnictví Reprodukční medicína

Článek vyšel v časopise

Česká gynekologie

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