Dexmedetomidine with low-dose ketamine for cataract surgery under peribulbar block in a patient with Huntington's chorea.

Huntington's chorea (HC) is a rare hereditary disorder of the nervous system. It is inherited as an autosomal dominant disorder and is characterized by progressive chorea, dementia, and psychiatric disturbances. There are only a few case reports regarding the anesthetic management of a patient with HC and the best anesthetic technique is yet to be established for those patients which are at higher risk of perioperative complications. We report the anesthetic management of a 64-year-old patient with HC admitted for cataract surgery.

INTRODUCTION

Huntington's chorea (HC) is a hereditary disorder of the nervous system affecting basal ganglia, mainly caudate nucleus. The transmission is autosomal dominant and responsible gene is chromosome 4. The prevalence of the disease is 4–10/100,000.[1] Onset is between 30 and 50 years of age.[2] Huntington's disease is characterized by a triad of symptoms: Personality changes, dementia, and choreiform movements.[3] The ominous motor symptom is dysphagia with dysfunction of pharyngeal muscles. Death is generally due to respiratory complications.[2] The anesthetic management of a patient with HC has particular challenges.[4]

CASE REPORT

A 64-year-old female weighing 55 kg, had been diagnosed with HC at the age of 54 years, not on treatment was posted for left cataract surgery. On examination, choreic movements in all limbs and head were observed. Other systemic examinations were within normal limits. Routine blood investigations and chest radiograph showed normal. Electrocardiogram (ECG) revealed left ventricular hypertrophy.

Patient was premedicated with injection ranitidine 50 mg, injection metoclopramide 10 mg intravenously. Routine monitoring included pulse oximetry, ECG, noninvasive blood pressure. Intravenous injection dexmedetomidine infusion was started at 1 mcg/kg over 10 min (loading) followed by 0.5 mcg/kg/h (maintenance). Patient was sedated, deeply asleep at the end of bolus infusion with complete cessation of chorea. However, when surgeon woke her up to inform and explain peribulbar block, she became awake and involuntary movements returned. When undisturbed she went to deep sleep with no movement. To ensure immobility, intravenous ketamine 0.2 mg/kg was given and the block was instituted uneventfully. Injection dexmedetomidine at the rate of 0.5 mcg/kg/h was continued till end of surgery. After 20 min when patient moved, ketamine (10 mg) was repeated. Total of 20 mg of ketamine was required intraoperatively. The surgery was uneventful, lasted for 45 min with satisfactory akinetic operative field. Postoperative course was uneventful as patient remained sedated, calm for 3 h without any involuntary movements. The patient was discharged from the hospital after postoperative day 3.

DISCUSSION

Huntington's chorea is a hereditary disease due to expansion of cytosine-adenine-guanine repetition in the Huntington gene, resulting in increased production of a mutant protein, Huntingtin. This protein leads to cell loss and atrophy, mainly of gamma aminobutyric acid (GABA)ergic striatal medium spinal output neurons of the caudate, putamen, and cortex. Antipsychotics, antidepressants, benzodiazepines, and antiepileptics are frequently used for symptomatic management. The anesthesiologist should be aware of potential interactions of such medications as general anesthesia can exacerbate psychiatric symptoms resulting in postoperative agitation, chorea, and psychosis.[5]

Main goals were to provide akinetic field for the surgeon, make patient comfortable and keep patient's reflexes intact and avoid general anesthesia with no exacerbation of symptoms.

The symptoms of HC are produced due to the deficiency of the inhibitory neurotransmitter GABA due to reduced activity of the enzyme glutamic acid decarboxylase. This enzyme is involved in the production of GABA in the striatum and the basal ganglia.[6] These symptoms aggravate further on voluntary activity, in stress but relieve during sleep. Therefore, we hypothesized that if we could put the patient to deep sleep that will mimic his nonrapid eye movement (NREM) sleep during the procedure, the surgery could be successfully performed. To serve this purpose we selected dexmeditomedine as the drug of choice.

Dexmedetomidine is selective alpha-2-adrenoceptor agonist acts on locus ceruleus (LC). Presynaptic activation of alpha-2-adrenoceptor in LC inhibits the release of norepinephrine resulting in sedative and hypnotic effect. LC is the site of origin for the descending medullospinal noradrenergic pathway, known to be an important modulator of nociceptive neurotransmission. Stimulation of the alpha-2-adrenoceptors in LC terminates propagation of pain signals leading to analgesia. Postsynaptic activation of alpha-2-adrenoceptors in the central nervous system (CNS) results in decreased sympathetic activity leading to hypotension and bradychardia. Activation of the alpha-2-adrenoceptors in CNS results in augmentation of cardiac vagal activity. Combined, these effects can produce analgesia, sedation, and anxiolysis.[7]

Dexmedetomidine-induced sedation resembles normal sleep. The participation of NREM sleep pathways explains why patients who appear to be “deeply asleep” are relatively easily aroused in much the same way as occurs with natural sleep. Animal study was found its sedative mechanism involves inhibition of the LC, which disinhibits ventro-lateral preoptic nucleus (VLPO) firing.[8] The increased release of GABA at the terminals of the VLPO inhibits tubomammilary nucleus firing, which is required for the sedative response. This type of sedation is branded “cooperative” or “arousable,” to distinguish it from the sedation induced by drugs acting on the GABA system, such as midazolam or propofol, which produce a clouding of consciousness.[9] We selected dexmedetomedine as sedation induced by it is dose-dependent with no respiratory depression.[10]

After loading dose of dexmedetomidine, patient fell asleep and involuntary movements abolished completely. When the patient was informed by surgeon about peribulbar block, she became fully awake, and involuntary movements reappeared. To further counteract and to maintain deeper plane of sedation we supplemented subanesthetic dose of ketamine.

Ketamine has minimal impact on a ventilator drive and intense analgesic properties. It interacts with N-methyl-D-aspartate, opioid, monoaminergic, muscarinic receptors and voltage gated Ca2+ channels but not with GABA receptors. Ketamine, when used with dexmedetomidine ketamine, induced cardiorespiratory effects, and postanaesthetic delirium are attenuated.[11] Our patient did not report hallucinations nor vivid dreams postoperatively. Use of ketamine is well-supported in eye surgeries when used along with other sedative agents and ophthalmic blocks.[12] Low-dose ketamine infusion effectively lowers postoperative narcotic requirements with no effect on mood, perception, and cognition.[11]

The side-effects of dexmedetomidine were not observed in our patient. The coexisting supplementation of ketamine may have contributed to the amnesia in this case.

CONCLUSION

Dexmedetomidine induced sleep abolished the choreic movements completely at the end of loading infusion, they recurred the moment patient got aroused suggesting that dexmedetomidine mimics NREM sleep pattern. Dexmedetomedine with low-dose ketamine along with peribulbar block proves to be useful in performing successful cataract surgery in such patients.