ISSN: 2644-1403
Jbili N1*, Bibiche L1, Jebbar N1, Maaroufi A1, Diai A2, Chkoura K2, Kechna H2 and Laoutid J2
Received: January 31, 2020; Published: February 11, 2020
Corresponding author: Nabil Jbili, Pole of Anesthesia, Resuscitation and Emergencies, Moulay Ismail-Meknes Military Hospital, Morocco
DOI: 10.32474/GJAPM.2020.02.000147
We report the observation of a 56-year-old female patient, with no specific medical history, operated on for acute cholecystitis. One week after the intervention, she presented a fatal fulminant hepatitis in less than two weeks, associating a deterioration of the general state with jaundice cutaneous mucosal frank, cytolysis and cholestasis important in addition to a deep hypo albuminemia and a very low prothrombin level. The toxicity of halothane has been incriminated due to the negativity of the etiological balance. Like the literature and this clinical case, the still frequent use of halothane in several countries must be reviewed.
Halothane is a halogen used for inhalation induction especially in children and the maintenance of anesthesia in adults and children. Its use is less and less widespread given its hepatic toxicity and its unfavorable hemodynamic repercussions, and the advent of new generations of more harmless halogens, however it remains in certain countries. Therefore, it is necessary to rationalize its use and take the necessary precautions.
We report the case of a 56-year-old patient, with no specific
medical history, who was operated on for acute cholecystitis, the
simple post-operative consequences of which allowed discharge
in 48 hours. The patient had no specific defects, including no
liver disease or atopy. She was not taking any medication and was
classified ASA I with a normal preoperative liver and kidney workup.
Cholecystectomy was performed by laparotomy under cost, under
general anesthesia. A standard induction by a morphine ‘Fentanyl°’, a
barbiturate ’Thiopental°’ and a non-depolarizing curare “Esmeron’’
at doses appropriate to the patient’s weight. The maintenance was
carried out with halothane with an equimolar O2/NO mixture. From
induction to waking, the patient remained hemodynamically and
respiratory stable. The extubation is performed on a table and after
an Aldrete score of 10 in the post interventional monitoring room,
the patient is transferred to the service. The consequences were
simple with resumption of transit the day after the intervention
and the exit was decided in 48 hours. One week after the day of
the intervention, the patient accused anorexia and asthenia in
addition to the appearance of a frank cutaneous mucosal jaundice
with dark urine evolving in a context of a pyrexia but especially of a
deterioration of the ‘’ general condition which motivated the patient
to consult urgently. Upon admission, the patient was non-pyretic,
time and space oriented and hemodynamically and respiratory
stable. His abdomen was un distended and flexible on palpation,
no hepatomegaly or splenomegaly. The bowel sounds were audible,
and the digital rectal examination was without abnormalities.
The mucosal skin examination revealed frank jaundice and
icteric conjunctiva. Cardiovascular, respiratory and neurological
examination was without abnormalities. The initial assessment
showed a hemoglobin level at 13.7g/dl, a hyperleukocytosis at
17940/μl (PNN and monocyte), thrombocytopenia at 89,000/μl, a
low prothrombin (TP) rate at 34% and a time active cephalin (TCA)
at 36 sec, cytolysis with ASATs (SGOT)=760 IU/L (21 times normal
value) ALAT=1042 IU/L (25 times normal value), cholestasis with
total Bilirubin at 246.17mg/l (20 times the normal value), direct
bilirubin=173.6mg/l (34 times the normal value) gGT=293 U/L,
PAL=199 U/L (1.2 times the normal value); the blood sugar level
was correct and the normal lipasemia at 46ui/l. On the infectious
level, apart from a CRP of 145.09mg/l, the ECBU remained sterile, the chest X-ray did not show any suspected parenchymal focus and
the blood cultures remained sterile. In addition, hepatic serologies
were found to be negative. The abdominal ultrasound showed a
simple intraperitoneal effusion blade without dilation of the intra
and extra hepatic bile ducts and the Bili-MRI was normal.
The therapeutic management consisted of rehydration with
eviction of all hepatotoxic drugs and monitoring of the count of the
blood formula and particularly the platelets, of the hydro electrolytic
assessment and the blood case. Evolution was marked by the
accentuation of the mucocutaneous jaundice and concentrated
urine and the worsening of the general state with a deterioration of
the consciousness. On the biological level, there has been a gradual
drop in the prothrombin level from 34% (on admission) to 16%
on the tenth day after admission, deep hypo albuminemia at 20g/l,
with worsening of cytolysis, cholestasis and thrombocytopenia.
On the contrary, hemoglobin and blood sugar remained stable and
kidney function was preserved.
Since its introduction on the market, halothane has been
implicated in the occurrence of postoperative hepatitis. Its
hepatotoxicity has been discussed for a long time, but currently,
there are many arguments that confirm its existence in humans and
animals. This diagnosis is more evocative in the absence of other
arguments in favor of another etiology [1,2]. These arguments are
based on retrospective and prospective Studies: -retrospective
studies concerning the circumstances of the occurrence of
postoperative hepatitis; the oldest and most important of which
is the National Halothane Study, covering 856,500 anesthesia’s
performed in the USA from 1959 to 1962. This study showed
the existence of unexplained massive hepatic necrosis after
administration of halothane and that the frequency of these
hepatitis was low, seven for 254,896 halothane administrations.
Other studies have confirmed that 82 to 95 percent of these hepatitis
infections are seen primarily after multiple administrations. 100 of
cases and spaced less than 28 days in 55 to 75p. 100 of hepatitis
observed after multiple exposures. - and prospective studies;
measuring biological parameters after halothane administration
[1].
The occurrence of post-halothane anesthetic hepatitis is often
spaced less than 28 days after multiple exposures in 65% of cases
[1], but in some cases, the occurrence may be early, within days or
even hours. follow, especially in the event of repeated and closeup
exposures [2-4]. After exposure to a toxic agent, hepatoxicity
is generally dose-dependent and therefore predictable, appearing
after a short delay (1-12 weeks). More rarely, it is idiosyncratic,
dose-independent and appears with a longer latency period (up to
12 months) [5]. The hepatic toxicity of halogenated agents of the
Immunoallergenic type is linked to the production of trifluoroacetic
acid [6,7], These terminal derivatives of metabolism form with
hepatic cytosolic proteins a neoantigen for which the organism
produces immunoglobulins G specifically directed against
hepatocytes [6]. The greater the metabolism of the halogenated
agent, the greater the quantity of neoantigens formed and the
higher the risk of cytolytic hepatitis. Thus, when using halothane
which is metabolized to 20%, its incidence is around 1/10000
anesthesia in adults. It is believed to be lower in children, around
1/200,000, although the metabolism of halothane does not differ
between children and adults [6].
The discovery of a hypersensitivity mechanism during
halothane hepatitis constitutes an interesting diagnostic
contribution, as highlighted in the general review of GOLDFARB
[5,2]. Other authors have noted the presence of antibodies to
halothane-treated rabbit hepatocytes in the serum of patients with
severe halothane hepatitis. Unfortunately, these explorations are
not common practice and do not represent a formal diagnostic
criterion [4,2]. In addition to individual vulnerability [5], Several
contributing factors have been implicated in the occurrence of
halothane hepatitis, hypovolemia, hypoxia, obesity, female sex and,
above all, repeated exposure to this anesthetic. However, according
to GOEDFARD, at least 5% of patients have an increase in SGPT after
the first administration of halothane [4,2]. Preexisting liver damage,
ischemic liver following an episode of low peripheral flow and the
type of surgery, those which cause manipulation of the hepatic
compartment or of long duration are also incriminated [3,5,8]. The
use of a barbiturate in anesthetic induction, as an enzyme inducer,
also promotes the appearance of hepatitis [2].
Chemotherapy promotes the severity of halothane hepatitis and
disrupts the metabolism of antimitotic by potentiating their toxic
effect. In 1980, SPIEGEL et al. reported two reports of fulminant
hepatitis following heavy chemotherapy and halothane anesthesia
[2,9]. The risk of halothane hepatitis is low in children (below the
age of 20) [4] and after the first anesthesia [9]. In adults this risk is
estimated at fulminant hepatitis for 35,000 halothane anesthesia’s.
For most of these toxic drugs or not, the management, after
elimination of the toxic is symptomatic [5]. The peculiarity of the
observation that we report is the absence of favorable factors apart
from the female sex and the use of a barbiturate type thiopental
at induction. The intervention was carried out without any notion
of hypovolemia or hemodynamic or respiratory instability and
the research in the history did not find any previous exposure to
halogens. In addition, biological and radiological explorations
have not objectified any etiology which could explain this hepatic
insufficiency suggesting the exposure to halothane. Indeed, given
the gravity of this attack, its rapidity of development and the
absence of predictive tests, it would be desirable, in adults as in
children, to space out the administration of halogens over time or
use other halogens that would cause little immunoallergic hepatitis
[3,9]. And if there is no restriction on the repeated use of halogens
in children, this judgment must be reviewed [4]. In addition, like
Spiegel et al, it is preferable to strictly ban the use of halothane in
patients who have received or are to receive antimitotic treatment
[9,10].
• I declare that the text has been read and approved by all
the authors.
• All authors declare that they have no conflict of interest.
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