Anaesthesia, 1984, Volume 39, pages 1222-1 224

C A S E REPORT

Gilbert’s syndrome as a cause of postoperative jaundice

S. T A Y L O R

Summary

A case of postoperative jaundice due to Gilbert’s syndrome in a previously healthy 19-year-old female
is presented. Signs and symptoms of jaundice developed on the second postoperative day and
resolved spontaneously after 5 days. The diagnosis and characteristics of Gilbert’s syndrome and other
related abnormalities and factors relevant to anaesthesia which affect bilirubin metabolism are
discussed.

Key words
Complications; jaundice, Gilbert’s disease.

Gilbert’s syndrome, a benign condition char-
acterised by mild and intermittent jaundice, has
an incidence which may be as high as 6% in the
population.’ The diagnosis is suggested by the
occurrence of unconjugated hyperbilirubinaemia,
with a normal conjugated bilirubin concentration
in the absence of structural liver disease or overt
haemolysis. It is important to make the diagnosis
so that extensive investigation of suspected liver
disease can be avoided and the patient can be
reassured of the excellent prognosis and normal
life expectancy.
Case history
A healthy 19-year-old girl presented with an
infected mastoid cavity which was to be explored
under general anaesthesia. The patient had re-
ceived a non-halothane anaesthetic 5 years earlier
for a spinal fusion, from which she made an
uneventful recovery. She had never had a previous
episode of jaundice nor was there any family
history of jaundice. Her only medication was an
oestrogen containing contraceptive pill which she
had taken for 2 years.
One hour before anaesthesia, she received
pethidine 75 mg and atropine 0.6 mg intra-
muscularly as premedication. Anaesthesia was
induced with thiopentone 250 mg and tracheal
intubation was facilitated with suxamethonium
50 mg. She was then allowed to breathe spon-
taneously and anaesthesia was maintained with
66% nitrous oxide in oxygen and halothane. The
anaesthetic and surgery were uneventful and no
blood was transfused.
On the first postoperative day the patient felt
nauseated and had a temperature of 37.8% which
was treated with prochlorperazine 12.5 mg intra-
muscularly. She continued to be nauseated and
mildly pyrexial on the second postoperative day

Susan Taylor, MB BS, FFARCS, Lecturer, Department of Anaesthesia, Foothills Hospital at the University of
Calgary, Calgary, Alberta, Canada.
Present appointment:Senior Registrar, Department of Anaesthetics, Leicester Royal Infirmary, Leicester.

0003-2409/84/121222 + 03 %03.00/0 @ 1984 The Association of Anaesthetists of Gt Britain and Ireland 1222

and at this time was noted to be jaundiced. There
was no hepatosplenomegaly or other stigmata of
liver disease. Blood testing revealed an uncon-
jugated hyperbilirubinaemia with a serum bili-
rubin of 97 p mol/litre. The jaundice lasted 5 days;
her only complaint was that of nausea.
The most common causes of a postoperative
increase in the unconjugated fraction of bili-
rubin are haemolysis (from surgical trauma or
blood transfusion) and Gilbert’s syndrome. As
the surgery had been minor and this patient had
not received a transfusion, the diagnosis of
Gilbert’s syndrome was made and confirmed by
means of the nicotinic acid provocation test. The
nature and significance of Gilbert’s syndrome was
fully explained to the patient and she was re-
assured that she would enjoy normal health.
Discussion
Jaundice is a not uncommon complication of
surgery. The differential diagnosis of post-
operative jaundice may be considered under three
basic pathophysiological mechanisms: increased
pigment load from overproduction of bilirubin,
impaired excretion of bilirubin due to hepato-
cellular damage, and obstruction of the extra-
hepatic bile d u c k 3 In clinical practice, multiple the serum bilirubin. However, since the mild
causes of jaundice may be present, especially in
patients who have shock, heart failure, hypoxae-
mia. and sepsis or who have received blood trans-
fusions, hepatotoxic drugs and certain anaesthetic
agents.
The upper limit of serum bilirubin is usually
taken to be 14 pmol/litre, but higher values
(17-50 pmol/litre) may be found in normal in-
dividuals, as has been demonstrated in some 5%
of healthy blood donors. When those suffering
from haemolysis or from overt liver disease have
been excluded, there remain the patients with
familial abnormalities of bilirubin metabolism, of
which Gilbert’s syndrome is the most ~ o m m o n . ~ Dubin-Johnson type there is a chronic, benign,
Gilbert’s syndrome is a benign condition
characterised by chronic, although often inter-
mittent, low grade, unconjugated hyperbili-
rubinaemia. Other tests of liver function, such
as transaminase values, are normal. Urobilinogen
is absent and hepatic histology is normal. The
condition is probably inherited as an autosomal
dominant, with the patient heterozygous for a
single mutant gene.5 The diagnosis is based on
family history, the duration of the condition, the
Gilbert ’s syndrome 1223
absence of any stigmata of hepatocellular disease
or splenomegaly, and is confirmed by the nicotinic
acid test. Intravenous administration of nicotinic
acid (50 mg) to patients with Gilbert’s syndrome
has been shown to cause a 2-3 fold increase in
plasma unconjugated bilirubin within 3 hours of
administration, whereas, in normal individuals or
in patients with haemolysis or liver disease, the
rise is less impressive.2 Commonly, the patient
with Gilbert’s syndrome may be asymptomatic
and the condition discovered during routine
blood testing or the patient may complain of
vague symptoms, such as abdominal pain, diar-
rhoea, fatigue and malaise.
Gilbert’s syndrome was first described 80 years
ago6 yet confusion still exists over the path-
ogenesis. The hyperbilirubinaemia is probably
due to difficulty in uptake and conjugation of
bilirubin by the liver cell. Patients with Gilbert’s
syndrome have reduced concentrations of the
microsomal enzyme bilirubin uridine diphospate
glucuronyl transferase,’ which catalyses the
conversion of unconjugated bilirubin t o con-
jugated bilirubin. This latter compound is water
soluble and excreted into the bile. The bilirubin
transferase enzyme can be induced by administra-
tion of phenobarbitone 60 mg three times a day
(adult dose), resulting in a return to normal of
hyperbilirubinaemia of untreated Gilbert’s
syndrome rarely leads to icterus, few patients
will gain cosmetic benefit from this treat-
ment.4
The other more rare conditions with abnor-
malities of bilirubin metabolism are the Crigler-
Najjar, Dubin-Johnson and Rotor syndrome^.^
In the Crigler-Najar syndrome there is a
deficiency of the conjugating enzyme in the liver.
Type I patients completely lack the enzyme and
usually die in the first year of life with kernicterus.
Type I1 patients respond to treatment with pheno-
barbitone and survive into adult life. In the
intermittent jaundice with conjugated hyper-
bilirubinaemia and bilirubinuria.* This syndrome
is characterised by striking amounts of pigment,
probably melanin, in the liver cell. The Rotor
variant of chronic familial conjugated hyper-
bilirubinaemia resembles the Dubin-Johnson
syndrome, the main difference being the absence
of brown pigment in the liver cell. Both the
Dubin-Johnson and Rotor syndromes have an
excellent prognosis.
1224 S. Taylor

Factors which increase bilirubin concentration

in Gilbert's syndrome are of interest to anaes- Acknowledgments
thetists. Any period of stress, e.g., surgery, inter- The author wishes to thank Mr McNab Jones
current illness or infection, causes jaundice of The Royal National Throat, Nose and Ear
associated with malaise, nausea, and often dis- Hospital, London, England, for permission to
comfort over the liver. Other precipitating factors report this case and Dr Jan Davies for her con-
include exercise, fatigue, alcohol intake and structive criticism during the preparation of the
menstruation. Furthermore, a period of starva- manuscript.
tion leads to a 2-3 fold increase in serum un-
conjugated bilirubin in patients with Gilbert's
References
~ y n d r o m e probably
,~ due to an increase during
fasting in serum fatty acids which compete with I. OWENSD, EVANSJ. Population studies on
Gilbert's syndrome. Journal of Medical Generics
bilirubin for excretion by the liver.l0 Quinn and 1975; 1 2 152-6.
Golan" reported two patients with Gilbert's 2. DAVIDSON AR, ROJAS-BUENO A, THOMFSON RPH,
syndrome who underwent oral surgery and WILLIAMS R. Reduced caloric intake and nicotinic
developed jaundice in the postoperative period acid provocation tests in the diagnosis of Gilbert's
in association with a reduced caloric intake. The syndrome. British Medical Journal 1975; 2 480.
3. LAMONTJT, ISSELBACHER KJ. Current concepts.
likelihood of hyperbilirubinaemia increases, of Postoperative jaundice. New England Journal of
course, if patients are booked for surgery late in Medicine 1973; 288: 305-7.
the day, as in this present case report. 4. SHERL~CK S.Diseases of the liver andbiliary system.
Pregnant patients and those taking oral con- 6th ed. Oxford: Blackwell Scientific Publications,
1981.
traceptives are less likely to develop jaundice, as 5. POWELL E, BILLING
LW, HEMINGWAY BH, SHER-
sex hormones induce hepatic glucuronyl trans- LOCK S. Idiopathic unconjugated hyperbili-
. ~ metabolism may also be affected
f e r a ~ e Drug rubinemia (Gilbert's syndrome). A study of 42
in Gilbert's syndrome. A case of prolonged action families. New England Journal of Medicine 1967;
of morphine in a patient with the syndrome was 277: 1108-12.
6. GILBERTA, LEREBOULLET P. La cholemie simple
reported in 1973.12 The most important meta- familiale. Semaine Medicale (Paris) 1901; 21:
bolic pathway for morphine metabolism is the 241-5.
formation of morphine-3 monoglucuronide by 7. BLACKM, BILLINGBH. Hepatic bilirubin UDP-
conjugation in the liver.13 Morphine and bili- glucuronyl transferase activity in liver disease and
Gilbert's syndrome. New England Journal of
rubin may share the same conjugation process Medicine 1969; 280: 1 2 6 7 1.
which includes both hepatic uptake and conjuga- 8. DUBIN IN, JOHNSONFB. Chronic idiopathic jaun-
tion with glucuronide. Therefore, patients with dice with unidentified pigment in liver cells. A new
Gilbert's syndrome may not metabolise morphine clinicopathologic entity with a report of 12 cases.
Medicine (Baltimore) 1954; 3 3 155-97.
normally and may exhibit a prolonged drug effect. 9. FEUHER BF, RICHARDD, REDEICER AG. The reci-
In addition, some drugs, such as novobiocin, procal relation between caloric intake and the
rifampycin and flavaspidic acid, may cause degree of hyperbilirubinemia in Gilbert's syn-
enzyme inhibition, thus precipitating jaundice in drome. New England Journal of Medicine 1970;
patients with Gilbert's ~ y n d r 0 m e . l ~ 283: 17G2.
10. GOLLAN JL, HOLEDR, BILLING BH. The role of
In summary, Gilbert's syndrome is one of the dietary lipid in the regulation of unconjugated
causes of postoperative jaundice. The diagnosis hyperbilirubinaemia in Gunn rats. Clinical Science
should always be considered and may be easily 1979; 57: 327-37.
confirmed by the nicotinic acid provocation test. 1 I. QUINN NW, GOLLAN JL. Jaundice following oral
Any patient with the condition presenting for surgery. Gilbert's syndrome. British Journal of
Oral Surgery 1975; 1 2 2858.
anaesthesia and surgery should be scheduled for 12. NISHIMURA TG, JACKSONSH, COHENSN. Pro-
operation early in the day, to limit the period longation of morphine anaesthesia in a patient with
of starvation and consideration should be given Gilbert's disease: report of a case. Canadian
to intravenous dextrose infusion. Pre-operative re- Anaestherbu' Society Journal 1973; u): 709-12.
13. GREENE NM. The metabolism of drugs employed
assurance and premedication will reduce stress. in anesthesia. Anesthesiology 1968; 2 9 327-60.
The influence of the condition on drug action and 14. STRUNINL. The liver and anaesthesia. London:
metabolism should also be remembered. W.B. Saunders, 1977.