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Case Reports

Perioperative Management of a Child With Glucose Transporter Type 1 Deficiency Syndrome: A Case Report

Yoshida, Tsubasa MD*; Shimizu, Kazuyoshi MD, PhD; Suzuki, Satoshi MD, PhD; Matsuoka, Yoshikazu MD, PhD; Morimatsu, Hiroshi MD, PhD

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doi: 10.1213/XAA.0000000000000727
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Abstract

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by SLC2A1 gene mutations causing reduced function of GLUT1 protein1 and inability of the central nervous system (CNS) to transport glucose. GLUT1DS is characterized by CNS dysfunction including epilepsy and developmental delay. A ketogenic diet (KD) containing high-fat proportions (fat-to-carbohydrate and fat-to-protein ratios of 3:1 or 4:1) should be initiated as early as possible2 because KD supplies ketone body (KB) as an alternative fuel in addition to providing an anticonvulsant effect. The perioperative management of patients on a KD generally focuses on blood glucose and KB concentrations to reduce the risk of convulsions. As GLUT1DS is accompanied by impaired cerebral cell glucose utilization, and as KB provides the brain with an alternative fuel during insufficient cerebral glucose supply, strict maintenance of high KB concentrations and tight glycemic control are more important in patients with GLUT1DS than in patients on a KD for other epileptic disorders. Meticulous intraoperative management is crucial because metabolic acidosis, surgical stress, and anesthetic drugs can affect the seizure threshold. We here report the successful management of a child with GLUT1DS undergoing laparoscopic gastrostomy under general anesthesia. The patient’s parents provided written permission to publish this report.

CASE DESCRIPTION

Table.
Table.:
Intraoperative Results of Blood Gas and Urine Analysis

The patient was a 2-year-old girl with a height of 87 cm and body weight of 11 kg. She had recurrent convulsions since the age of 4 months and was receiving anticonvulsant medications. Low cerebrospinal fluid glucose suggested GLUT1DS. Genetic screening confirmed the diagnosis at 1 year 8 months. After KD initiation, neurologic symptoms including irritability, inability to maintain a sitting position, and hypertonia improved. However, convulsions recurred after the age of 2 years. After anticonvulsant medication had been adjusted to oral levetiracetam 450 mg/d, the patient was stable with symptomatic localized epilepsy and delayed psychomotor development. The child was scheduled to undergo laparoscopic gastrostomy under general anesthesia. Under the preoperative care of pediatricians, a blood KB concentration of 5000–6000 μmol/L (normal range: 28–120 μmol/L) and a urine KB concentration of 3+ (Labstix; Siemens, Germany; 1+ = 15, 2+ = 40, 3+ = 80, 4+ = 160 mg/dL) were maintained. Water intake was restricted to 70 mL·kg−1·day−1. Surgery was scheduled 4 hours after eating the last KD because a duodenal feeding tube was in place. Preoperative laboratory data other than blood KB concentration and urinalysis were within normal ranges. After confirmation that the blood KB concentration was 6975 μmol/L and urinary KB concentration 3+, the child was transferred to the operating room without any premedication. Monitoring included electrocardiogram, peripheral oxygen saturation and end-tidal carbon dioxide concentration, invasive arterial blood pressure, and bispectral index. General anesthesia was induced with 5% sevoflurane. After intravenous access, endotracheal intubation was facilitated by 0.6 mg/kg rocuronium. Anesthesia was maintained with 5% desflurane, 0.1–0.25 μg·kg−1·minute−1 remifentanil, and a total of 60 μg of fentanyl. We administered glucose-free Ringer’s acetate solution at a restricted infusion rate of 5 mL/h. We assessed blood glucose concentration every 30 minutes and urine KB concentration every hour (Table). We carefully avoided hyperventilation during induction of anesthesia and maintained hyperventilation after endotracheal intubation to compensate for the metabolic acidosis after intubation (Table). When the arterial pH decreased below 7.35, we twice administered 5 mL of 1.7% sodium bicarbonate. Blood glucose and urine KB concentrations were maintained at 79–90 mg/dL and 4+, respectively. Bispectral index values were maintained at 30–40 without signs of seizure activity. Intraoperative cardiovascular and respiratory vital signs remained stable. Laparoscopic gastrostomy proceeded uneventfully. Estimated blood loss was minimal, and the total amount of administered Ringer’s acetate solution was 28 mL. For postoperative analgesia, the wound was infiltrated with 7 mL of 0.2% ropivacaine at the end of surgery, and a 200 mg acetaminophen suppository was administered. Surgery and anesthesia lasted for 58 and 126 minutes, respectively. Postoperatively, the endotracheal tube was removed in the operating room and the child was transferred to the intensive care unit (ICU). Here we continued to administer glucose-free Ringer’s acetate solution at a rate of 10 mL/h. KD was resumed at 3 hours postoperatively. Total duration of fasting was 10.5 hours. During the ICU stay, blood glucose and urine KB concentrations were maintained at 79–131 mg/dL and 4+, respectively. The patient was discharged from the ICU to a general ward on postoperative day 1. Convulsions were not observed throughout the perioperative period.

DISCUSSION

We report the successful perioperative management of a child with GLUT1DS. There is only a single report in abstract form on the perioperative management of a patient with GLUT1DS.3

GLUT1DS is a rare disease with an estimated prevalence rate of 1 in 90,000.1 GLUT1 is an essential protein that facilitates the transport of glucose across the blood–brain barrier. GLUT1 deficiency results in impaired glucose transport into the brain. The clinical symptoms of GLUT1DS are characterized by CNS dysfunction. Once GLUT1DS is suspected or diagnosed, a KD should be started as early as possible in addition to conventional antiepileptic treatments to prevent epilepsy.2 KD supplies KBs that can cross the blood–brain barrier and provide the brain with an alternative fuel during insufficient cerebral glucose supply, thereby preventing a glucose deficiency–induced energy crisis. KB increases the synthesis of glutamate and γ-aminobutyric acid as the inhibitory neurotransmitter and decreases glutamate release by competitive inhibition of vesicular glutamate transporters.4 Epilepsy will be suppressed by these mechanisms. Thus, in patients on a KD, sufficient KB concentration needs to be maintained and hyperglycemia avoided.

Tight control of KB concentration is the most important aspect in the perioperative management of a patient with GLUT1DS. In general, blood and urine KB concentrations should preoperatively be maintained at >4000 μmol/L and >2+, respectively, to prevent seizures in epileptic patients on a KD.5,6 Unlike other epileptic disorders, cellular energy in GLUT1DS is limited. We administered as little as possible glucose-free solution to avoid the dilution of KB concentration. However, it is unclear whether strict fluid restriction is necessary for patients on a KD. Whereas fluid restriction was recommended in some reports,6,7 a recent guideline recommends individual adjustment of fluid intake based on weight and biochemistry results.8 If hypotension occurs during fluid restriction, vasopressor therapy is indicated.

The relation between medications and seizure potential is important. Medications known to impair GLUT1 function such as phenobarbital, diazepam, and chloral hydrate should be avoided.2 Anesthetics with minimal epileptogenic potential should be selected. Sevoflurane may cause seizure-like electroencephalographic activity7 and can decrease the seizure threshold at >1.5 minimum alveolar concentration when combined with hyperventilation.9 We induced anesthesia with 5% sevoflurane avoiding hyperventilation. However, it might have been safer to provide appropriate premedication, secure intravascular access, and then perform an intravenous induction of anesthesia. We maintained anesthesia with desflurane and hyperventilated the child because the combination of desflurane and hyperventilation does not decrease the seizure threshold in patients with intractable epilepsy, and desflurane has little effect on liver metabolism.7,9 Several reports have described the anesthetic management of epileptic patients on a KD,6,7,10–13 but GLUT1DS patients were not included. Inhalational anesthetics were used in approximately half of the patients for inducing anesthesia and in almost all of them for maintenance of anesthesia. Currently, there is no consensus regarding which anesthetic is most effective in preventing convulsions in this patient population.

Special attention needs to be paid to the type of intravascular fluid, metabolic acidosis, and pain control. The relation between different types of crystalloid solutions and the occurrence of seizures in patients with epilepsy has not been investigated. Ringer’s acetate solution may be preferable to normal saline because acetate combines with hydrogen ions thereby attenuating acidosis.7 Active correction of metabolic acidosis by bicarbonate is recommended because metabolic acidosis can decrease the seizure threshold.9 Serum bicarbonate should be maintained at >18 to 20 mEq/L.10,14 We corrected intraoperative metabolic acidosis by sodium bicarbonate when the blood pH was <7.35. Pain control is important for patients on a KD because pain tends to facilitate metabolic acidosis and hyperglycemia.7

In conclusion, we successfully managed a child with GLUT1DS undergoing laparoscopic surgery. Further experience is required to establish the optimal perioperative management of patients with GLUT1DS.

DISCLOSURES

Name: Tsubasa Yoshida, MD.

Contribution: This author drafted the article.

Name: Kazuyoshi Shimizu, MD, PhD.

Contribution: This author helped revise the manuscript.

Name: Satoshi Suzuki, MD, PhD.

Contribution: This author helped revise the manuscript.

Name: Yoshikazu Matsuoka, MD, PhD.

Contribution: This author helped revise the manuscript.

Name: Hiroshi Morimatsu, MD, PhD.

Contribution: This author approved the article.

This manuscript was handled by: Hans-Joachim Priebe, MD, FRCA, FCAI.

REFERENCES

1. US National Institutes of Health, National Library of Medicine, Genetics Home Reference. GLUT1 deficiency syndrome. Published June 27, 2017. Available at: https://ghr.nlm.nih.gov/condition/glut1-deficiency-syndrome. Accessed January, 23, 2018.
2. De Giorgis V, Veggiotti P. GLUT1 deficiency syndrome 2013: current state of the art. Seizure. 2013;22:803811.
3. Mecoli M, Pratap J. Anesthetic management of a patient with GLUT1 deficiency syndrome. Available at: http://www2.pedsanesthesia.org/meetings/2014winter/syllabus/submissions/aandp/nonmods/NM-207.pdf. Accessed January, 23, 2018.
4. McNally MA, Hartman AL. Ketone bodies in epilepsy. J Neurochem. 2012;121:2835.
5. White H, Venkatesh B. Clinical review: ketones and brain injury. Crit Care. 2011;15:219.
6. McNeely JK. Perioperative management of a paediatric patient on the ketogenic diet. Paediatr Anaesth. 2000;10:103106.
7. Ichikawa J, Nishiyama K, Ozaki K, Ikeda M, Takii Y, Ozaki M. Anesthetic management of a pediatric patient on a ketogenic diet. J Anesth. 2006;20:135137.
8. van der Louw E, van den Hurk D, Neal E. Ketogenic diet guidelines for infants with refractory epilepsy. Eur J Paediatr Neurol. 2016;20:798809.
9. Maranhão MV, Gomes EA, de Carvalho PE. Epilepsy and anesthesia. Rev Bras Anestesiol. 2011;61:232254.
10. Valencia I, Pfeifer H, Thiele EA. General anesthesia and the ketogenic diet: clinical experience in nine patients. Epilepsia. 2002;43:525529.
11. Matsuura K, Morimoto Y, Sugimura M, Taki K, Maeda M, Niwa H. [Case report of dentatorubral pallidoluysian atrophy in a patient on a ketogenic diet]. Masui. 2009;58:762764.
12. Saito J, Kimura N, Watanuki R. [General anesthesia with propofol for a pediatric patient on a ketogenic diet]. Masui. 2011;60:733735.
13. Hinton W, Schwartz RH, Loach AB. Diet induced ketosis in epilepsy and anaesthesia. Metabolic changes in three patients on a ketogenic diet. Anaesthesia. 1982;37:3942.
14. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134:28022818.
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