Services on Demand
- Cited by SciELO
- Access statistics
Print version ISSN 0034-7094
On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.54 no.3 Campinas May/June 2004
Anesthesia in a patient with Gilbert's syndrome. Case report*
Anestesia en paciente con síndrome de Gilbert. Relato de caso
Fabiano Timbó Barbosa, TSA, M.D.I; Silvio Marcos Lima dos Santos, M.D.II; Joaquim Sávio Menezes Batista da Costa, M.D.II; Ronaldson Correia Bernardo, M.D.II
IProfessor de Farmacologia do Centro
de Ensino Superior de Maceió; Anestesiologista da Santa Casa de Misericórdia
IIAnestesiologista da Santa Casa de Misericórdia de Maceió
BACKGROUND AND OBJECTIVES: Gilbert's
syndrome is a chronic benign disease leading to recurrent jaundice and major
unconjugated bilirubin increase that may be toxic after the use of routine medication.
This report aimed at describing the anesthetic approach in Gilbert's syndrome
patient submitted to videolaparoscopic surgery.
CASE REPORT: Female patient, 22 years old with Gilbert's syndrome, submitted to videolaparoscopic surgery under general anesthesia with propofol, alfentanil, succinylcholine, atracurium and isoflurane. There were no evidences of toxicity during anesthesia. Postoperative recovery was satisfactory and patient was discharged three days later.
CONCLUSIONS: Gilbert's syndrome patients may be safely submitted to general anesthesia without toxicity, provided factors leading to glucuronosyltransferase activity decrease are avoided.
Key Words: DISEASES: Gilbert's syndrome; SURGERY, Videolaparoscopic
JUSTIFICATIVA Y OBJETIVOS: La síndrome
de Gilbert es una enfermedad crónica benigna la cual lleva a la ictericia
recurrente con grande aumento de la bilirrubina no conjugada, que puede llevar
a la toxicidad después del uso de medicamentos utilizadas en la práctica
diaria. El objetivo de este relato es describir la conducta anestésica
en una paciente con síndrome de Gilbert, sometida a cirugía videolaparoscópica.
RELATO DEL CASO: Paciente del sexo femenino, con 22 años, portadora de la síndrome de Gilbert fue sometida a cirugía videolaparoscópica bajo anestesia general con propofol, alfentanil, succinilcolina, atracúrio e isoflurano. No hubo señales de toxicidad durante la anestesia. La paciente presentó recuperación pós-operatoria sin intercurrencias y recibió alta hospitalar después de tres días.
CONCLUSIONES: El paciente portador del síndrome de Gilbert puede ser sometido a la anestesia general de forma segura sin el aparecimiento de toxicidad desde que sean evitados los factores que puedan llevar a la diminución de la actividad de la glicuroniltransferasis.
Gilbert's syndrome is a chronic benign disease characterized by increased indirect bilirubin and clinically manifested as jaundice, which may appear before, during or after anesthesia.
Patients have jaundice when submitted to stress or exercises, during active menstrual cycle bleeding or when fasting 1. The incidence of this disease is estimated in 6% of general population 2, being more frequent in males 1-3.
Bilirubin is originated as from heme ring catabolism which may come from aged hemoglobins, bone marrow erythrocytes by ineffective erythropoiesis, or from blood proteins, especially liver blood proteins 3. After being uptaken by the reticuloendothelial system 3, heme-oxygenase breaks down hemoglobin in biliverdin, carbon monoxide and iron 4. Biliverdin-reductase converts biliverdin into bilirubin 4 at a rate of 4 mg/kg/day 3. This bilirubin is liposoluble and apolar. It may bind to albumin and its free fraction may cross blood-brain barrier 3. Bound to albumin, it is taken to the liver where it suffers conjugation with glycuronic acid becoming hydrosoluble and polar.
Jaundice is a clinical presentation characterized by yellowish skin, mucosa or eyes, when bilirubin is above 2.5 to 3 mg/dL 3.
Pregnant women or those under oral contraceptives develop less jaundice because in such conditions there is liver glucuronosyltransferase induction 2.
Syndrome may be diagnosed by family history, duration of the disease, lack of other liver diseases justifying jaundice, and jaundice triggered by predisposing factors, such as fasting, menstruation, stress and exercises 1. Diagnosis may be confirmed by jaundice improvement after fenobarbital and worsening after intravenous nicotinic acid 1.
This report aimed at presenting the case of Gilbert's syndrome patient submitted to general anesthesia for videolaparoscopic correction of gastroesophageal reflux.
Caucasian, female patient, 22 years old, 49 kg, with Gilbert's syndrome since she was 12 years old. Patient was admitted for videolaparoscopic correction of gastroesophageal reflux. Her history revealed jaundice after prolonged fasting, after insomnia periods and during active menstrual cycle bleeding. Vomiting was not resolved with metoclopramide.
Preanesthetic approach was 8-hour fasting with surgery scheduled for the first morning period, without any preanesthetic medication
Monitoring in the operating room consisted of cardioscopy, pulse oximetry, noninvasive blood pressure and capnography instituted only after tracheal intubation. Venous access was achieved with 20G catheter, infusion of 5% glucose solution and intravenous omeprazol (40 mg) and ondansetron (4 mg). Balanced general anesthesia was induced 30 minutes after with fast track and Sellick's maneuver using propofol (150 mg), succinylcholine (50 mg) and alfentanil (2500 µg). Tracheal intubation was easy with a 6.5 mm diameter tube with cuff, with no evidences of respiratory tract intercurrences. Mechanically controlled ventilation was installed and maintained throughout the procedure. Anesthesia was maintained with lactated Ringer's solution (10 mL.kg-1.h-1), isoflurane, 1 L.min-1 oxygen and atracurium (25 mg), with repetition of half dose every 30 minutes until surgery completion. Ketoprofen (100 mg) and dexamethasone (10 mg) were administered 30 minutes after surgery completion. Intravenous nalbuphine (10 mg) was administered after tracheal extubation for postoperative analgesia.
Surgery lasted 120 minutes and stage II anesthesia recovery was achieved in the operating room.
Emergence was calm and without intercurrences. Patient was referred to her room and was discharged three days later without complications.
The group of biochemical reactions making drugs polar, hydrosoluble and easily excreted is called biotransformation or metabolism and is enabled by enzymes, being the liver the core organ for such process.
During metabolism the liver is able to include some endogenous substances, such as glycuronic acid, to the functional group of drugs 5,6, forming glycuronides. The enzyme responsible for such reaction is known as glucuronosyltransferase. These glycuronides are easily excreted by kidneys thus preventing drug overdose that could lead to toxicity and death.
Since there is low glucuronosyltransferase activity in Gilbert's syndrome 7, though it is necessary for some drugs excretion, there is the risk for anesthetic toxicity with the possibility of a catastrophic outcome.
It is important for the anesthesiologist to understand conditions leading to decreased glucuronosyltransferase activity in Gilbert's syndrome patients to be submitted to anesthesia, to prevent intraoperative toxicity. They are fasting, active menstrual cycle bleeding, infections and other stress-inducing conditions. For Gilbert's syndrome patients it is desirable a previous evaluation by the anesthesiologist; that surgery be performed in the first morning period to minimize fasting and waiting stress; glucose infusion before surgery 2; to avoid surgery during active menstrual cycle bleeding; to assure satisfactory postoperative analgesia.
It is routine in our service to admit patients the day of the surgery, since contact with relatives may decrease preoperative stress, hospital stay and the need for preanesthetic medication. No home medication was prescribed since, in addition to impairing patient's transportation to the hospital, it could lead to adverse events outside the hospital environment.
In our case, glucose was infused before surgery to prevent jaundice triggering-factor, and was not maintained during surgery since it is already well defined in the literature that surgery represents a moment of major stress with increased glycemia as neuroendocrine-metabolic response. If response to stress is abolished, intraoperative lactate could be converted into glucose by glyconeogenesis through Cori's cycle 8. Intraoperative glucose is justified when there is risk for hypoglycemia, such as in diabetes mellitus, prolonged parenteral nutrition, neonatology, fasting for more than 24 hours, malnutrition, liver dysfunction, surgeries after major physical traumas 8.
Gastric content aspiration syndrome was described by Mendelson in 1946 as the presence of gastric content in the pulmonary tree 9. When the volume is above 25 mL and pH is lower than 2.5 there may be life-threatening pulmonary injury. This complication may be present in pregnant women, alcoholic, comatose, convulsive or obese patients, in patients with gastroesophageal reflux or hiatal hernia 9. To minimize this risk we decided for fast-track induction 10 and protons pump blocker associated to ondansetron. Succinylcholine was used for fast-track induction due to its fast onset allowing for early tracheal intubation, and short duration, allowing muscle activity recovery in case of failure.
Halothane was not used during anesthesia because it is an halogenate with high liver metabolism, reaching 20% 11 and for its potential to cause postoperative jaundice. This halogenate may promote two types of liver dysfunction classified as Types I and II. In type I, dysfunction is mild, transient, is spontaneously resolved and may be present in up to 20% of patients 11. In type II, dysfunction is uncommon and is due to the presence of antibodies that appear after repeated exposures and may lead to severe liver dysfunction with jaundice within two to 15 days after general anesthesia 10. Isoflurane has 0.2% liver metabolism 12. All volatile agents decrease total liver blood flow and this decrease is maximum with halothane and minimum with isoflurane 4. Isoflurane is the most adequate volatile anesthetic agent for patients with liver dysfunction 12.
General intravenous anesthesia may also be considered for Gilbert's syndrome patients, but there are some caveats: thiopental and ketamine change liver function tests depending on the dose 12 and may impair postoperative investigation of jaundice; etomidate may lead to adrenal failure by 17 alpha-hydroxilase and 11 beta-hydroxilase enzymes inhibition, with inhibition of cortisol, aldosterone, 17-hydroxiprogesterone and corticosterone synthesis 13. These drugs should be avoided and propofol and remifentanil should be preferred. Propofol has a higher clearance than liver blood flow suggesting an extra-liver excretion pathway 13. Remifentanil is an ester degradeted by plasma and tissue esterases 14, preventing liver function impairment.
Causes of postoperative jaundice are major hematomas, blood transfusion, underlying liver disease, ischemic or hypoxic injury, substance-induced injuries, intra-hepatic cholestasis, postoperative cholecystitis, postoperative pancreatitis, retained common billiary duct stone and Gilbert's syndrome 4. Most common causes are excessive bilirubin production by reabsorption of major hematoma and post-transfusion erythrocyte cleavage 4,12. In case of postoperative jaundice, it is recommended that all causes be investigated.
Gilbert's syndrome patients may be safely submitted to general anesthesia without toxicity, provided factors leading to glucuronosyltransferase activity decrease are avoided.
01. Radu P, Atsmon J - Gilbert's syndrome - clinical and pharmacological implications. Isr Med Assoc J, 2001;3:593-598. [ Links ]
02. Taylor S - Gilbert's syndrome as a cause of postoperative jaundice. Anaesthesia, 1984;39:1222-1224. [ Links ]
03. Andeolii TE, Bennett JC, Carpenter CCJ et al - Icterícia, em: Andeolii TE, Bennett JC, Carpenter CCJ et al - Cecil Medicina Interna Básica, 4ª Ed, Rio de Janeiro, Guanabara Koogan, 1998;314-317. [ Links ]
04. Morgan Jr GE, Mikhail MS - Fisiologia Hepática e Anestesia, em: Morgan Jr GE, Mikhail MS - Anestesiologia Clínica, 2ª Ed, Rio de Janeiro, Revinter, 2003;587-599. [ Links ]
05. Mello AC - Biotransformação das Drogas, em: Silva P - Farmacologia, 6ª Ed, Rio de Janeiro, Guanabara Koogan, 2001;61-67. [ Links ]
06.Correia MA - Biotransformação dos Medicamentos, em: Katzung BG - Farmacologia Básica e Clínica, 5ª Ed, Rio de Janeiro, Guanabara Koogan, 1994;37-45. [ Links ]
07. Simon JB - Manifestações Clinicas das Hepatopatias, em: Bondy PK, Dilts Jr PV, Douglas RG et al - Manual Merck de Medicina, 16ª Ed, São Paulo, Roca, 1992;861-876. [ Links ]
08. Macuco MV, Macuco OC, Bedin A et al - Uso de soluções glicosadas em cirurgias. Hábito ou necessidade? Rev Bras Anestesiol, 1996;46:415-422. [ Links ]
09. Udelsmann A - Complicações Anestésicas, em: Yamashita AM, Takaoka F, Auler Jr JOC et al - Anestesiologia SAESP, 5ª Ed, São Paulo, Atheneu, 2001;1029-1055. [ Links ]
10. Caruy CAA - Anestesia em Urgências, em: Yamashita AM, Takaoka F, Auler Jr JOC et al - Anestesiologia SAESP, 5ª Ed, São Paulo, Atheneu, 2001;1015-1026. [ Links ]
11. Beltrame Neto J, Vicente EK, Fortis EAF - Hepatite por halotano. Relato de caso. Rev Bras Anestesiol, 1997;47:148-151. [ Links ]
12. Savaris N, Freitas JCM - Complicações em Anestesia, em: Manica JT - Anestesiologia Princípios e Técnicas, 2ª Ed, Porto Alegre, Artes Médicas, 1997;780-806. [ Links ]
13. White PF, Gonzáles JM, Hemelrijck JV - Farmacologia dos Anestésicos Intravenosos, em: Rogers MC, Tinker JH, Covino BG et al - Princípios e Prática de Anestesiologia, 1ª Ed, Rio de Janeiro, Guanabara Koogan, 1996;837-853. [ Links ]
14 .Nociti JR - Anestesia Venosa: Farmacologia, em: Yamashita AM, Takaoka F, Auler Jr JOC et al - Anestesiologia SAESP, 5ª Ed, São Paulo, Atheneu, 2001;523-538. [ Links ]
Dr. Fabiano Timbó Barbosa
Rua Comendador Palmeira, 113/202 Farol
57051-150 Maceió, AL
Submitted for publication June 10, 2003
Accepted for publication August 14, 2003
* Received from Santa Casa de Misericórdia de Maceió, AL