Anesth Analg 2004;99:1376-1378
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000134796.83697.CD
PEDIATRIC ANESTHESIA
Suspected Central Anticholinergic Syndrome in a 6-Week-Old Infant
Peter J. Kulka, MD DEAA*,
Hakki Toker, MD ,
Jörg Heim, MD*,
Alexander Joist, MD , and
Jens Jakschik, MD
*Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, and
Department of Surgery, Prosper-Hospital, Recklinghausen, Germany; and
Department of Anesthesiology and Intensive Care Medicine, Evangelisches Krankenhaus Oberhausen, Oberhausen, Germany
Address correspondence and reprint requests to P. J. Kulka, MD, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Prosper-Hospital, Mühlenstr. 27, D-45659 Recklinghausen, Germany. Address email to peter.kulka{at}prosper-hospital.de
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Abstract
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A 6-wk-old male infant became unresponsive after an uneventful general anesthetic for hernia repair. His symptoms were consistent with central anticholinergic syndrome. He appeared to awaken after treatment with IV physostigmine in a dose of 0.04 mg/kg. Because of the recurrence of sedation, a second physostigmine infusion was administered, which again led to transient arousal. Finally, the patient awoke spontaneously after 24 h and recovered uneventfully.
IMPLICATIONS: A 6-wk-old boy was unarousable after an uneventful general anesthetic. After eliminating other causes, a central anticholinergic syndrome seemed possible. IV physostigmine successfully reversed the comatose state and confirmed the diagnosis.
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Introduction
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The term "central anticholinergic syndrome" (CAS) was first introduced by Longo (1) in 1966. The syndrome may consist of either agitation, including seizures, restlessness, hallucinations, and disorientation, or of signs of depression, such as stupor, coma, and respiratory depression. The syndrome may be induced by anticholinergic drugs such as atropine or scopolamine but has also been observed after administration of opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, cimetidine, etomidate, propofol, nitrous oxide, and volatile inhaled anesthetics (2). After general anesthesia, the incidence of CAS has been reported to be 1%–9% (3,4). Although CAS in adult patients has often been described (5–11), reports of the syndrome in pediatric patients are rare (12–14). We report a case of suspected CAS in a 6-wk-old infant.
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Case Report
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A male, 6-wk-old former preterm infant (birth at the 36th week of gestation) weighing 3.8 kg was scheduled for a hernia repair. Before induction of anesthesia, no sedatives were administered. In the operating room an infusion was started with 2.5% glucose in Ringer’s solution (40 mL/h) and general anesthesia was introduced with atropine 0.03 mg, methohexitone 15 mg, and tramadol 7 mg. After orotracheal intubation, anesthesia was maintained with sevoflurane 1.5 minimum alveolar concentration in a mixture of oxygen/nitrous oxide 50%/50%. Minute ventilation was adjusted to an end-expiratory CO2 value of 35 mm Hg. Glucose analysis at the start and before the end of anesthesia confirmed normoglycemia. The hernia repair took 20 min. After the completion of surgery, sevoflurane application was discontinued and 12 min later the child’s trachea was extubated. After tracheal extubation oxygen saturation remained stable between 95% and 100% on room air. His heart rate ranged between 130 and 150 bpm and his mean arterial blood pressure was 45 mm Hg. Neurologic examination revealed no pathologic findings (pupils isochor, both responding to light, no nystagmus, normal reflex status, no nuchal rigidity). Suctioning of the oropharynx caused coughing and undirected defense movements but, undisturbed, the child remained deeply asleep. The patient was transferred to the intensive care unit for further observation. In the afternoon, about 6 h after induction of anesthesia, the child was still deeply asleep, only reacting to painful stimuli. Neurologic examination again revealed no pathologic findings (normal pupillary responses to light, no nystagmus, normal extremity reflexes, no nuchal rigidity). His body temperature was 37.5°C. The patient’s cardiorespiratory function (heart rate, SpO2) had been normal throughout the postoperative period. Hyper- and hypoglycemia, hypercapnia, and electrolyte imbalance were excluded by laboratory examinations. Because the child had been healthy before surgery, and because other reasons for his protracted unresponsiveness were unlikely, the diagnosis of CAS was made. An infusion of physostigmine 0.04 mg/kg was started and administered over 20 min. He developed hypersalivation and increased bowel movements during the infusion. Immediately after the end of infusion the child awoke and started to cry. Breastfeeding was initiated immediately. However, symptoms recurred after 90 min and another infusion of physostigmine (0.03 mg/kg) was initiated. Again, the child awakened and stayed awake for 120 min but then fell asleep again. This time we decided not to intervene again. The child slept through the entire night and awoke without further intervention on the next day, more than 24 h after the end of anesthesia. The further course was uneventful, and the child was discharged 3 days after surgery.
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Discussion
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This is the first report of suspected CAS in an infant less than 1 year of age. Holland (14) described the case of a 9-year-old boy who developed CAS with hallucinations and incontinence 24 hours after scopolamine patch application. In another reported case, CAS resulted in deep sedation, inadequate response to stimuli, and reduced muscular tone of the upper airway leading to airway obstruction (12). In a 5-year-old boy CAS occurred after premedication with midazolam and a short volatile anesthetic. In this case, diagnosis was difficult as a result of a history of convulsions, acetylcholinesterase deficiency, and chronic corticosteroid medication (13). In our case, the diagnosis was based on the fact that other possible reasons for delayed recovery were apparently absent.
Acetylcholine is an important transmitter in the central nervous system (CNS). A relative deficiency of acetylcholine at cholinergic synaptic endings in the CNS is the underlying cause of CAS. Relative acetylcholine deficiency might be the result of occupancy of central cholinergic receptor sites by specific drugs or an insufficient release of acetylcholine. The condition may result in central signs such as somnolence, confusion, amnesia, agitation, hallucinations, dysarthria, ataxia, delirium, stupor, coma, and peripheral signs such as dry mouth, dry skin, tachycardia, visual disturbances, and difficulty in micturition (4). Individuals may have differing predispositions for the development of CAS (2). In the study of Link et al. (3) the incidence of CAS was significantly more frequent in women undergoing hysterectomy compared with women after other gynecological procedures. The reason for this increased prevalence is unknown.
The differential diagnosis includes pharmacological reasons, such as persistence in the effects of anesthetics, sedatives, opioids or muscle relaxants. Alcohol abuse, drug abuse, or intoxicants may also cause decreased or altered mental response. Metabolic or endocrine disturbances, such as hyper- or hypothermia, acid-base disorders, hypothyroidism, hyper- or hypoglycemia, and hyperpyrexia, or neurological reasons such as cerebral ischemia, intracranial masses, cerebral edema or trauma, acute psychosis, and epilepsia must all be considered and eliminated before the diagnosis of CAS can be made.
The diagnosis is confirmed by the administration of physostigmine, an acetylcholine esterase inhibitor that, in contrast to other acetylcholine esterase inhibitors like pyridostigmine, is able to cross the blood-brain barrier where it transiently increases the acetylcholine concentrations at cholinergic neurons. Its peripheral muscarinic effects are negligible (2). According to an investigation by Hartvig et al. (15) physostigmine plasma concentrations of at least 2–5 ng/mL are required to achieve an adequate analeptic effect. The infusion of 2 mg physostigmine over 20 minutes has been recommended for adult patients. Possible side effects occur as a consequence of increasing acetylcholine concentrations at cholinergic neurons and include nausea and vomiting, hypersalivation, bronchoconstriction, bowel movement, lacrimation, and bradycardia. One case of atrial fibrillation has been described after physostigmine administration (16). Therefore, monitoring of cardiorespiratory function is mandatory during the application of the antagonist. As a consequence of its short duration of action because of hydrolytic decomposition it has to be expected that the effect fades away within 20 to 60 minutes.
The occurrence of a CAS is a rare event after anesthesia. This case demonstrates that CAS is possible even in younger children.
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References
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Accepted for publication May 18, 2004.
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Abstract
Introduction
