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a 67-year - old female patient with adrenal insufficiency in drug - induced hepatic failure previously had a cancer on the left breast , which had been treated by modified radical mastectomy followed by an unknown regimen of adjuvant chemotherapy .
thereafter , she had experienced jaundice with mental change and had been diagnosed with drug - induced liver failure . despite supportive care , her stuporous mental status did not return , making her a candidate for liver transplantation .
although she was semicomatose , her vital signs were stable and there was no evidence of sepsis .
mmol / l and k concentration of 4.8 - 5.4 mmol / l ( table 1 ) . a rapid adrenocorticotropic hormone ( acth ) stimulation test was performed to diagnose adrenal insufficiency .
her preoperative random total cortisol concentration was 9.0 g / dl ( adrenal insufficiency : < 10 g / dl ) .
thirty minutes after stimulation with 250 g synacthen , her delta cortisol concentration was 4.9 g / dl ( adrenal insufficiency : < 9 g / dl ) .
based on guidelines for the diagnosis of corticosteroid insufficiency in critically ill patients , she was diagnosed with adrenal insufficiency .
the patient was started on hydrocortisone therapy ( 50 mg , tid ) preoperatively , and it was maintained during liver transplantation .
hemodynamic data were recorded in real time during surgery using an online personal computer interfaced with a signal processing software ( windaq , dataq instrument , akron , oh ) .
thirty minutes after surgical incision , the patient 's mean arterial blood pressure ( abp ) started to fluctuate and decreased to less than 60 mmhg without significant blood loss . because intermittent bolus administration of ephedrine was not effective , she was infused continuously with dopamine ( 5 - 10
g / kg / min ) , dobutamine ( 5 g / kg / min ) and norepinephrine ( 0.15 - 0.2 g / kg / min ) , starting from the pre - anhepatic phase of liver transplantation ( table 1 ) .
, she was administered 172.5 mg of methylprednisolone ( 3 mg / kg ) for immunosuppression . immediately after reperfusion
, she was administered 40 g of an epinephrine bolus due to severe hypotension . however , although she was supported by increasing dose of inotropics and vasopressors after graft reperfusion , her abp continued to fluctuate until the end of the operation .
although she was maintained on hydrocortisone postoperatively , inotropics could not be tapered and hemodynamic instability continued ( table 1 ) . on postoperative day 9 , the patient developed atrial fibrillation , and a chest radiograph showed pneumonic infiltration . on postoperative day 11 , the patient died due to pneumonia and septic shock .
, there is a high incidence of adrenal insufficiency in critically ill patients with liver disease .
harry et al .   reported that hemodynamically unstable patients with acute hepatic dysfunction showed significantly lower serum cortisol levels of acth stimulation test .
they also revealed that the steroid replacement was associated with dose reduction of vasopressor , but not survival , in patients with adrenal insufficiency in liver failure .
furthermore , marik et al .   have observed a pathophysiologic association between adrenal insufficiency and low concentrations of high - density lipoprotein , the preferred source of seteroidogenic substrates in the adrenal gland , in patients with liver failure and in post - liver transplant recipients .
although hydrocortisone replacement started immediately after diagnosis of adrenal insufficiency , her hemodynamic status was unstable and she required continuous infusion of inotropics during and after liver transplantation .
therefore , she likely had hepatoadrenal syndrome , with adrenal insufficiency playing a role in her cardiovascular instability during and after liver transplantation .
because most of liver transplant recipients receive supplementary corticosteroids as postoperative immunosuppressants , adrenal insufficiency has been rarely documented in those patients . after the development of steroid - free immunosuppression , several reports have shown adrenal insufficiency in post - liver transplant recipients .
for example , adrenal insufficiency , as manifested by severe multiple organ dysfunction , was observed in a post - liver transplant recipient who had not been administered with steroid immunosuppressants . that patient had been diagnosed with adrenal insufficiency 40 days after liver transplantation and
was successfully treated with corticosteroid . however , there is little report focused on adrenal insufficiency that occurred before liver transplantation .
our report is a case of a liver transplant recipient to be diagnosed preoperatively with adrenal insufficiency , showing marked abp fluctuation during liver transplantation surgery .
it is well known that the basic concept of adrenal insufficiency is the inadequate activation of hypothalamic - pituitary - adrenal axis with cortisol release to illness and stress .
even though the present patient showed relatively stable hemodynamic parameters before glucocorticoid replacement , she was treated with hydrocortisone throughout the hospital course after confirming adrenal insufficiency . however , surgical stress may not be tolerated and cause severe hemodynamic instability during liver transplantation despite hydrocortisone replacement therapy , implying importance of adrenal function in liver transplantation .
several previous studies on patients with liver failure and adrenal insufficiency have focused on sepsis or septic conditions and survival by corticosteroid administration .
previous studies have reported that corticosteroid therapy has beneficial effects on survival and hemodynamic stability in patients with liver failure and septic shock   and in post - liver transplant recipients [ 3,11 - 13 ] .
however , consistent with findings showing that corticosteroid therapy may not improve survival in vasopressor - dependent patients with adrenal insufficiency and liver disease , our patient with suspected hepatoadrenal syndrome did not effectively respond to corticosteroid therapy , eventually expired due to pneumonia and septic shock after liver transplantation .
the specific mechanisms underlying these controversial effects of steroid therapy are unknown , but warrant further investigation .
it has been well known that hemodynamic complications in patients with liver failure may be affected by several factors . for examples , low systemic vascular resistance , high cardiac output , combined cirrhotic cardiomyopathy , massive bleeding and coagulopathy , and metabolic status during liver transplantation
hemodynamic instability in the present patient during and after liver transplantation was not explained completely by the general pathophysiology of liver failure .
because arterial ph , electrolytes , lactate level , and intravascular volume status during liver transplantation surgery were maintained adequately , adrenal insufficiency diagnosed preoperatively was thought to be an important reason for the marked abp fluctuation during and after liver transplantation surgery in our patient .
however , we could not exclude the above mentioned pathophysiological effects . in conclusion , we found that a patient with adrenal insufficiency suffered severe hemodynamic instability during and after liver transplantation , reinforcing the importance of hepatoadrenal syndrome .
these findings indicate that perioperative adrenal function should be monitored carefully in liver transplantation recipients with severe hemodynamic fluctuation .
adrenal insufficiency , which is related to hemodynamic instability and increased mortality , has been reported in patients with advanced liver disease regardless of the presence of septic conditions . in this regard 
 , the hepatoadrenal syndrome has been recently proposed as adrenal insufficiency in critically ill patients with liver disease . 
 we describe here a 67-year - old female patient with hepatic failure and adrenal insufficiency . 
 the patient showed stable vital signs and no evidence of sepsis preoperatively . despite hydrocortisone replacement and inotropics administration , 
 severe intraoperative hemodynamic instability was observed . 
 hydrocortisone administration was continued postoperatively , nevertheless inotropics could not be tapered . 
 on postoperative day 11 , the patient died due to pneumonia and septic shock . 
 hepatoadrenal syndrome may have played a key role in her severe hemodynamic fluctuation and poor outcome , reinforcing the importance of adrenal function in the liver transplantation surgery .