We report our anaesthetic management of a patient with Haddad syndrome, a rare phenotype comprising both congenital central hypoventilation syndrome (CCHS or Ondine's curse) and Hirschsprung disease (aganglionosis). Written consent for this report was obtained prior to publication.
In CCHS, mutations of the PHOX2B gene lead to a loss of function in the respiratory central pattern generator. Voluntary breathing is intact while awake. However, during sleep, there is no central control of ventilation, resulting in alveolar hypoventilation. Patients require lifelong artificial ventilation while asleep, and in severe cases, even during the daytime.1 Most patients are diagnosed at an early age, but there have been reports of clinically attenuated late-onset phenotypes as well.2 Additionally, disorders mimicking Ondine's curse may be seen in patients with acquired severe brain damage. Diaphragmatic pacemakers may offer an alternative therapy for those requiring chronic ventilator support.3
Hirschsprung disease is a neurocristopathy of the hindgut caused by failed embryological migration of ganglion cells leading to functional bowel stenosis. It may be found in 20% of patients with CCHS.4 Treatment consists of surgical excision of aganglionic segments.
Both disorders may be interpreted as extreme variants of a general autonomic nervous system dysfunction (ANSD).1 Accordingly, gastro-oesophageal motility, temperature regulation and glucose homeostasis may be impaired. Cardiac dysfunction can comprise arrhythmias and syncope as well as hypotension/hypertension. Chronic hypoxaemia may lead to pulmonary hypertension and right ventricular failure in CCHS.5
A 17-year-old boy underwent combined oesophagogastroscopy and sigmoidoscopy under general anaesthesia for histopathological diagnosis. For several years he had been complaining of being underweight (50 kg, BMI 18.4 kg m−2), abdominal pains and diarrhoea. Extensive aganglionosis had led to a total colectomy. He had been diagnosed with Haddad syndrome as an infant and received non-invasive positive pressure ventilation during sleep.
At evaluation, the boy presented without any limitations to daily life. Medical history revealed one episode of syncope, and an inconstant pattern of hypotension and hypertension indicating ANSD. Previous anaesthetic procedures had been uneventful except for one anaphylactic reaction to latex as an infant.
To avoid central respiratory depressant effects, we prescribed no premedication. For the procedure we established routine monitoring and inserted one peripheral intravenous cannula. Because of the patient's history of an anaphylactic reaction to latex, he received triple prophylaxis of prednisolone, clemastine and ranitidine. Sedating side-effects of antihistamines are common, but were accepted after weighing up the possible risks. All equipment inside the operating room was latex-free.
The patient's lungs were pre-oxygenated with 80% oxygen for 5 min via a face mask in order to avoid resorption atelectasis but still obtain a high oxygen load.
For induction, remifentanil was administered at 0.5 μg kg−1 min−1 for 4 min. The throat was sprayed with lidocaine 40 mg. Lidocaine 40 mg and etomidate 0.4 mg kg−1 were given intravenously and the trachea was intubated orally without any muscle relaxant. Anaesthesia was maintained using desflurane 7.3 to 8.5% and remifentanil 0.3 μg kg−1 min−1. Monitoring included bispectral index (BIS), which registered a range of 40 to 60 throughout the procedure. We used pressure-controlled ventilation adjusted towards a normal end-tidal carbon dioxide tension around 4.6 kPa. The inspired oxygen concentration was 40 to 50%.
During anaesthesia we closely monitored the function of the autonomous nervous system. Measurements of blood glucose and lactate concentrations were performed every 30 min (via venous blood gas analysis) as global metabolic parameters. Body temperature was monitored using a nasal probe. A preheated operating room (27°C), warming blanket and fluid warmers prevented cooling. Two episodes of hypotension following repositioning during endoscopy emphasised dysfunctional circulatory control, but were easily controlled by administration of the low-potency sympathomimetic cafedrine 20 mg and theodrenaline 1 mg. An alternative explanation may be hypovolaemia caused by irrigation with polyethylene glycol in preparation for the procedure; a low-serum ionised calcium concentration (1.06 mmol l−1) on venous blood gas analysis would support such an explanation.
At the end of the procedure, all anaesthetics were discontinued. Owing to the favourable kinetic profiles of remifentanil and desflurane there was rapid recovery of consciousness. Mandatory ventilation was maintained until tracheal extubation because chemoreceptor changes in pH or carbon dioxide tension cannot trigger breathing in CCHS.1 End-tidal desflurane concentration was less than 0.6% within 2 min and after another 8 min, the patient woke up and immediately breathed spontaneously.
Observation in our paediatric ICU was uneventful. For the remainder of the day the patient stayed alert and no hypoventilation was detected. Ventilation during the following night was without incident. A follow-up call 8 weeks after anaesthesia revealed no further problems.
Short-acting anaesthetic agents are crucial in patients with CCHS. We decided to use remifentanil as an analgesic because of its reliably short context-sensitive half-line and we chose etomidate as the hypnotic because of its minimal haemodynamic effects, beneficial in a patient with suspected ADSN. Propofol was excluded because of prolonged complete atrioventricular block in a patient with CCHS.6 We also ruled out thiopental because of reports of bradycardia after induction in children.7
We decided not to use muscle relaxants because of their unwanted side-effects; nondepolarising blocking agents may cause respiratory depression through anticholinergic effects in the carotid body8 and succinylcholine is known to trigger bradyarrhythmias through vagolysis. Instead, we induced deep anaesthesia by using high doses of remifentanil and also reduced laryngeal reflexes by applying lidocaine both topically and intravenously. Oral intubation was easy, confirming reports that CCHS patients have no increased risk of a difficult airway.3
For maintenance of anaesthesia in CCHS, the literature provides conflicting recommendations. Some authors disapprove of volatile anaesthetics; they argue that sufficient ventilation is needed to ensure clearance at the end of anaesthesia.3 The pharmacokinetic properties of desflurane, with rapid and reliable washout after discontinuation, seem to make it a favourable choice of anaesthetic.
Acknowledgements relating to this article
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