Central alveolar hypoventilation syndrome (CAHS) is an extremely rare condition characterized by failure of the autonomic control of breathing during sleep.1 The term “Ondine’s curse” is more commonly used for cases of congenital central alveolar hypoventilation (CCHS), but it is also applied to acquired cases. The term originates from a German myth about Ondine, an oceanic nymph who punished her unfaithful lover with the loss of all movements and functions that did not involve his conscious will. He was thus condemned to remain awake forever; otherwise, he would stop breathing and die. A similar condition develops in patients with CAHS—a rare neuropathologic syndrome characterized by an inadequate central respiratory drive with a blunted response to increasing arterial carbon dioxide tension (PaCO2)—which results in hypoventilation and apnea leading to hypercarbia and hypoxemia.2 The hypoventilation and apnea occur typically during periods of sleep when patients demonstrate a blunted sensitivity to hypercarbia.2 Unless early invasive ventilation is instituted, these prolonged periods of hypoxia cause these patients to develop pulmonary hypertension and cor pulmonale.3 Diaphragm pacing stimulation is a new treatment recently approved by the Food and Drug Administration which provides direct diaphragmatic stimulation to assist breathing. It has been used successfully with tetraplegic patients and those who suffer from amyotrophic lateral sclerosis (ALS).4-6 It has been shown to improve quality of life and to extend survival in patients with advanced respiratory muscle weakness.7 This case report describes the anesthetic management and considerations for a patient with CAHS undergoing DPSS implantation. Our patient provided written informed consent for publication prior to submission.

Case description

Our patient was a 50-yr-old female of small stature with a body mass index of 23. She had developed CAHS at the age of 13 after suffering from encephalitis. For several months, she was managed conservatively with a rocking bed, and she then had bilateral phrenic nerve pacemakers implanted, which successfully managed her condition for 24 yr. At age 37, nocturnal positive pressure ventilation (PPV) to her lungs via mask was added after she contracted pneumonia. Unfortunately, owing to progressive dysfunction of her phrenic nerve pacemakers, she developed worsening chronic ventilatory failure and eventual cor pulmonale. In addition, her history included rapid atrial flutter precipitating episodic cardiac failure. Though an ablation procedure was considered, the arrhythmia was ultimately controlled with oral beta-blockers. Her list of medications included diuretics, warfarin, and metaprolol. The warfarin was discontinued four days prior to her surgery, and she was given subcutaneous low-molecular-weight heparin until the day prior to surgery.

The patient’s 2D echocardiogram showed a normally functioning left ventricle and a mildly enlarged right ventricle with severely reduced function. The right ventricular systolic pressure (RVSP) was 32 mmHg and the valves were normal. A complete blood count revealed polycythemia with a hemoglobin concentration of 192 g·L−1. Her baseline arterial blood gases on room air were pH 7.41, PCO2 65, PO2 43, HCO3 42, and SaO2 94%. The electrocardiogram showed atrial flutter, and her chest x-ray showed a small chronic left pleural effusion and bilateral atelectasis.

On the morning of surgery, the patient was breathing with the assistance of her volume-controlled ventilator which was set to assist-control mode with a tidal volume of 700 mL and 16 breaths·min−1. In the operating room, standard American Society of Anesthesiologists monitoring was used in addition to a radial arterial line, fluid warmer, and a forced-air warming blanket. Cardiac pacing/defibrillating pads were applied to the patient prior to induction, and a cardiac arrest cart was kept in the operating room in case the patient required cardioversion for atrial tachyarrhythmia. Prior to induction, the patient lungs were preoxygenated with 100% O2 via bag-valve-mask assist ventilation. Anesthesia was induced with fentanyl 0.7 μg·kg−1 iv and propofol 2.3 mg·kg−1 iv, and the patient’s trachea was intubated without any neuromuscular blockade. The patient was maintained with an air/oxygen mixture and a total intravenous anesthetic technique using propofol 50-160 μg·kg−1·min−1 and remifentanil 0.125-0.5 μg·kg−1·min−1. The patient’s tidal volume was maintained at 450-500 mL using volume control ventilation, and the respiratory rate was maintained at 8-10 breaths·min−1 to target a partial pressure of carbon dioxide (ETCO2) which correlated with a PaCO2 reflective of the patient’s baseline value measured by serial arterial blood samples.

A laparoscopic surgical procedure was performed, and care was taken to keep the intra-abdominal pressures <12 cm H2O during peritoneal insufflation. No change in blood pressure was noticed with slow intraperitoneal insufflation. After mapping the diaphragm, two electrodes were embedded into the musculature of the abdominal aspect of each hemidiaphragm, and the electrodes were then connected to an external stimulator for electrical activation of the diaphragm. The procedure was completed within three hours.

An arterial blood gas analysis performed on F i O2 at 0.7 prior to emergence from anesthesia showed pH 7.42, PCO2 51, PO2 84, HCO3 31, and SaO2 99%. The diaphragmatic pacemakers were then tested. Stimulation produced diaphragmatic contractions which were evident under direct visualization through the laparoscopic camera and by the appearance of a curare notch on the ETCO2 curve. The ventilator was switched off, and spirometry showed adequate flow-volume curves with tidal volumes that varied from 250-290 mL (Figure). Infusions were discontinued and emergence from anesthesia occurred within one to two minutes. Once the patient was awake and obeying commands, her trachea was extubated. The patient was transferred to the intensive care unit postoperatively with diaphragm pacer-driven ventilation assisted intermittently with PPV by bag-valve-mask to maintain a normal SpO2. After a brief requirement for PPV by mask in the immediate postoperative period, the patient was discharged on postoperative day one (F i O2 0.3, pH 7.48, PCO2 36, PO2 85, HCO3 27, and SaO2 98%) to the Home Ventilation Assessment Unit for ongoing pacemaker adjustment and management.

Figure
figure 1

Pressure-volume loops for patient. A. Breathing spontaneously with no diaphragmatic stimulation; and B. Breathing spontaneously with diaphragmatic stimulator. Section B clearly shows the notch (white arrow) indicating diaphragmatic stimulation which provides an extra tidal volume of 100-150 mL to the patient’s spontaneous breath

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Discussion

We report the perioperative management of a patient with acquired CAHS who presented for laparoscopic DPSS implantation.

The term “Ondine’s Curse” was used initially by Severinghaus and Mitchell8 in 1962 when they described three patients with acquired CAHS occurring following high cervical and brainstem surgery. These patients could breathe when awake and when told to breathe, but mechanical lung ventilation was needed to treat severe central sleep apnea. In 1970, Mellins et al. 9 described the first case of an infant who presented with all the typical signs and symptoms of congenital CAHS, generally termed CCHS. While less common, acquired CAHS has been identified in conditions that either directly or indirectly affect the brainstem respiratory centre, including medullar tumours,10 infection (particularly poliomyelitis), upper cervical trauma, some mitochondrial diseases, degenerative diseases (e.g., multiple sclerosis), or non-specific anoxic ischemic insults.11-13 Our patient stated that she had suffered from encephalitis at age thirteen, and since then, she required ventilatory support. Brainstem encephalitis has been described as a cause of acquired CAHS,14 and it has been postulated that the infection can cause small vessel vasculitis, which may impair blood flow to the brainstem.15 The exact cause in our patient is unclear.

Central alveolar hypoventilation syndrome—a rare neuropathologic syndrome characterized by an inadequate central respiratory drive with a blunted response to PaCO2—results in hypoventilation and apnea leading to hypercarbia and hypoxemia.2 The hypoventilation and apnea occur typically during periods of sleep when patients demonstrate a blunted sensitivity to hypercarbia.2 The mainstay of long-term care for children with congenital CAHS is PPV through a permanent tracheotomy.15-17 In contrast, our patient had been managed with a combination of phrenic nerve pacing and PPV by mask. As these treatments failed, her abnormal breathing and prolonged periods of hypoxia led to pulmonary vascular remodelling and eventual development of pulmonary hypertension, right heart failure, and subsequent arrhythmia.

Anesthetic goals for patients with CAHS involve minimizing respiratory depression in order to avoid prolonged mechanical lung ventilation. In view of their pulmonary hypertension, regional anesthesia, such as a carefully titrated lumbar epidural, appears to be the anesthetic of choice for CAHS patients where applicable. Spinal anesthesia should be avoided as it may cause a profound sympathetic blockade, decrease in venous return, and bradycardia, which can lead to right heart failure.18 Combined spinal epidural technique has been used successfully in patients with severe pulmonary hypertension during pregnancy.19 However, if general anesthesia is necessary, it is prudent to intubate the patient’s trachea and control lung ventilation in all cases, as these patients will not breath spontaneously when asleep. Relatively short-acting anesthetic agents are preferred. In our case, both remifentanil and propofol provided optimal anesthetic qualities, and no long-acting opioid was used. Inhalation anesthetics were avoided, as their clearance would depend on adequate postoperative lung ventilation which may be deficient with patients suffering from CAHS. The absence of a neuromuscular blocking agent was necessary as the surgery required constant intraoperative mapping of the diaphragm. Short-acting muscle relaxants, such as succinylcholine, could have been used for tracheal intubation; however, due to hypotonia, it has been recommended to avoid succinylcholine until more data are available concerning its use in this patient group.2 The absence of muscle relaxation did not affect the course of our anesthetic as the patient’s trachea was intubated easily with the help of propofol and fentanyl; moreover, due to her weak respiratory muscles and her underlying condition, our patient did not offer much resistance to mechanical lung ventilation.

Other goals in this case included avoidance of hypoxia, hypercarbia, acidosis (respiratory or metabolic), hypo or hypervolemia, and hypothermia and provision of adequate anesthesia and pain control. These steps were taken to prevent a pulmonary hypertensive crisis and right ventricular failure. Hypoxia, hypercarbia, and acidosis can increase PVR directly or indirectly and should be avoided.18 Hypovolemia can cause impaired RV perfusion, and hypervolemia can cause pulmonary congestion and RV failure.18 Particular attention was devoted to temperature regulation because patients with congenital CAHS can have problems with central temperature control.2 Also, hypothermia could worsen the patient’s pulmonary hypertension.18

Monitoring included routine monitors and arterial blood pressure. A central venous catheter would have allowed us to guide adequate cardiac preload and would have provided a route for cardiac pacing and vasopressor or inotrope administration, if required. However, due to the patient’s history of uncontrolled atrial flutter leading to cardiac failure, it was decided to avoid catheter insertion due to the small risk of provoking another arrhythmia. In case the patient did develop an unstable arrhythmia, external pacing pads were applied, and a defibrillator was kept in the room for emergency cardioversion. We also considered treatment strategies in the event of a pulmonary hypertensive crisis, such as inhaled prostacyclin analogs, inhaled nitric oxide, and intravenous phosphodiesterase 5 inhibitors (e.g., milrinone).

Regarding extubation of the trachea, the patient could breathe only if sufficiently awake to respond; therefore, the anesthesia was designed to allow the patient to meet the extubation criteria earlier. With diaphragmatic stimulation, the patient was able to generate adequate tidal volumes of 290-300 mL, and once the patient was awake, her trachea was successfully extubated. The intensive care unit was notified to have a mechanical ventilator on standby if required.

Unlike the majority of phrenic nerve stimulators which are inserted through thoracic or cervical incisions,20 in our case, the surgeon placed electrodes directly into the musculature of the diaphragm via an abdominal laparoscopic approach. This approach required a pneumoperitoneum which potentially could have caused a reduction in preload, acidosis due to CO2 insufflation, and hypoxia due to increased intra-abdominal pressure.21 All of these conditions could have worsened our patient’s pulmonary vascular resistance and induced RV failure.18 To avoid any problems, the patient was kept warm, good communication was maintained with the surgeon to minimize intra-abdominal pressures, and a close eye was kept on the ventilatory parameters to maintain baseline ETCO2 and prevent hypoxia.22

In conclusion, CAHS is a rare neuropathological disorder with profound perioperative concerns for the anesthesiologist. It is imperative for the anesthesiologist to have a good understanding of the condition and its secondary complications. In addition, it is recommended that good communication occur between the anesthesiologist, surgeon, and respiratory physician concerning the management of these patients.