Front. Med. DOI 10.1007/s11684-015-0398-7

CASE REPORT

Severe hepatoxicity caused by aspirin overdose: a case report Zhuping Cao1, Shiqi Liu (

✉)2, Jianhua Niu3, Bing Wei4, Jie Xu5

1

Department of Nursing, School of Medicine, Shihezi University, Shihezi 832002, China; 2Department of Pediatric Surgery, The Affiliated Northwest Women’s and Children’s Hospital, Xi’an Jiaotong University, Xi’an 710003, China; 3Third Department of General Surgery, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832002, China; 4Department of Medical Administration, The First Affiliated Hospital, Shihezi University, Shihezi 832002, China; 5Department of Emergency, The First Affiliated Hospital, Shihezi University, Shihezi 832002, China

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2015

Abstract We report here the rare case of a 61-year-old man with multiple organ dysfunction caused by an aspirin overdose (4 g orally). The patient presented with a fever that reached 39.2 °C, a peptic ulcer, and massive upper gastrointestinal bleeding. His blood test results were as follows: white blood cell count, 1.8  109/L; absolute lymphocytes, 0.4  109/L; absolute neutrophils, 1.2  109/L; and electrolyte disturbances. A computed tomography (CT) scan showed evidence of bilateral inferior pulmonary infection and acute pancreatitis. Thick dark bile with visible floccule was drawn via a percutaneous transhepatic cholangiodrainage (PTCD). Klebsiella pneumoniae was detected in microbiological bile tests. Two years later, the patient died of chronic liver failure. Keywords

aspirin; side effects; liver failure

Presentation of case A 61-year-old man took 4 g of aspirin orally (without the advice of a medical professional) to cope with a 2-day spontaneous fever that began on September 2, 2007. Although the fever subsided, the patient developed gradually worsening epigastric pain, and vomited approximately 200 ml of bloody gastric content 3 h after the pain began. The abdominal pain and vomiting were persistent, leading the patient to seek medical care. An abdominal radiograph from another hospital showed an intestinal obstruction, but the prescribed therapy was wholly ineffective. Three days later, when his symptoms had worsened and his body temperature was 38 °C, he was admitted to the General Surgery Department of our hospital. Before this incident, the patient had been healthy, with a history of smoking for more than 30 years, but with no history of heavy drinking, diabetes, hypertension, autoimmune disorders, tuberculosis, or hepatitis. The patient was emotionally despondent and a physical examination indicated that his temperature had risen to 39.2 °C and that he had a respiratory rate of 21 breaths/

Received July 30, 2014; accepted April 16, 2015 Correspondence: [email protected]

min, a pulse rate of 122 beats/min, and blood pressure of 110/70 mmHg. He had clear bilateral breath sounds without pleural frictions. His abdomen was full and symmetric, but lacked gastrointestinal form, peristaltic movements, and varicosity. His entire abdomen was tender, particularly in the right upper quadrant, accompanied by local guarding and rebound tenderness. The liver, spleen, and gallbladder were impalpable. The shifting dullness sign was negative. His bowel sounds were active, at 6–7/min, without gurgling. The patient’s initial laboratory tests results are shown in Table 1. Chest and abdominal radiography indicated bilateral pulmonary and bronchial infection with a pellet shadow in the area of the right pulmonary apex, and a possible bowel obstruction. Clinical examination excluded biliary calculi, benign bile duct stricture, biliary malignancy, and congenital biliary malformation. After being given antibiotics, fluids, and treatments to suppress gastric acid production and pancreatic enzymes, the patient’s symptoms, such as abdominal distension and pain, improved transiently. However, 3 days after being admitted, the patient’s condition worsened and he developed a moderate fever and hyperglycemia. In addition to receiving treatment for his symptoms, the patient was given insulin and octreotide through a continuous intravenous injection. On September 11, the patient complained of pain and discomfort in his left upper

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Multiple organ dysfunction caused by aspirin overdose

Table 1 Laboratory test results Results Parameter

September 6, 2007

September 11, 2007

September 25, 2009

White blood cell count

1.8  109/L

12.1  109/L

3.5  109/L

Neutrophils

68.4%

82.9%

83.5%

Absolute lymphocytes

0.4  109/L

0.37  109/L

0.3  109/L

Absolute neutrophils

1.2  10 /L

1.6  10 /L

2.9  109/L

9

9

Lymphocytes

23.9%

24%

9.7%

Hemoglobin

155 g/L

132 g/L

154 g/L

Platelets

224  109/L

178  109/L

99  109/L

Serum sodium

130 mmol/L

125 mmol/L

132.1 mmol/L

Serum potassium

3.14 mmol/L

4 mmol/L

4.59 mmol/L

Serum chloride

91 mmol/L

88 mmol/L

94.1 mmol/L

Serum calcium

1.92 mmol/L

1.75 mmol/L

2.14 mmol/L

Serum amylases

Negative

Negative

Negative

Urinary amylases

Negative

Negative

Negative

Urine bilirubin

Positive

Positive

Positive

Urine protein

Positive

Positive

Positive

Urine acetone bodies

Positive

Negative

Negative

Urine occult blood

Positive

Negative

Positive

Acetone body

Positive

Positive

Positive

Urine glucose

Positive

Negative

Negative

Fecal pus cells

Positive

Negative

Negative

HAsAg

Negative

Negative

Negative

HBsAg

Negative

Negative

Positive

HCsAg

Negative

Negative

Negative

HEsAg

Negative

Negative

Negative

Total protein

60.7 g/L

47.1 g/L

66.2 g/L

Albumin

39 g/L

22.6 g/L

41.2 g/L

Total bilirubin

90.2 μmol/L

310.2 μmol/L

99 µmol/L

Direct bilirubin

55 μmol/L

207.0 μmol/L

72.2 µmol/L

Indirect bilirubin

35.2 μmol/L

103.2 μmol/L

26.8 µmol/L

ALT

142 U/L

133 U/L

7790 U/L

Aspartate aminotransferase

54 U/L

61 U/L

5293 U/L

Lactate dehydrogenase





6573 U/L

quadrant and back. It was noted that his skin and scleras appeared yellowish and that he had a fever (39.0 °C). A second round of laboratory tests were performed; the results are summarized in Table 1. Ultrasonography revealed a slightly enlarged gallbladder with thickened walls, a 1.0-cm wide common bile duct, and a mildly enlarged pancreas with exudation suggestive of acute cholecystitis or acute pancreatitis. A computed tomography (CT) scan revealed evidence of a bilateral inferior pulmonary infection, with local pleural thickening and adhesion at the posterior inferior edge, and peripancreatic exudation. Follow-up blood and urinary amylase tests were normal. Based on the ultrasound and CT findings, a diagnosis of acute pancreatitis was made. The patient was submitted to percutaneous transhepatic cholangiodrainage (PTCD) which resulted in the with-

drawal of 50 ml of thick dark bile with visible floccule. No pus cells were observed in the withdrawn bile, but Klebsiella pneumoniae was detected in microbiological bile tests. Over 3 days of PTCD, the drained bile became normal in appearance and the patient’s symptoms, including his fever and abdominal pain, improved. By 15 days postadmission, the jaundice had subsided and the patient’s serum protein level was normal. He was discharged after 22 days of being hospitalized. Twenty-one months after being discharged, the patient was readmitted into our hospital due to a sudden cerebral hemorrhage. A CT scan indicated subarachnoid hemorrhage and a subdural hematoma. The condition was cured by emergency intracranial hematoma evacuation, but the patient was left with residual mental impairment. Two months later, the patient experienced sudden

Zhuping Cao et al.

vomiting of bloody stomach contents. A physical examination showed that the patient had a temperature of 36.6 °C, a pulse rate of 96 beats/min, a respiratory rate of 24 breaths/min, and blood pressure of 140/75 mmHg. The patient’s skin, mucosa, and sclerae were moderately yellowed without spider telangiectasia or varicosity. The hepatic dullness area was not enlarged, epigastric tenderness was present without rebound tenderness, and ascites and lower limb varicosities were detected. The results of his final laboratory tests are shown in Table 1. Notably, the presence of hepatitis B virus surface antigen (HBsAg) was detected. The patient was diagnosed with hepatic failure due to severe hepatitis. During his hospital stay, the patient suffered from recurrent vomiting of bloody stomach contents (up to 700 ml) and died of hepatic failure despite aggressive pharmacological treatment.

Discussion Isolated adverse effects of aspirin are common in clinical practice, but multiple organ dysfunction induced by aspirin overdose, as seen in this patient, is rare. Aspirin is commonly used as an antipyretic and analgesic. Additionally, aspirin is recommended for prophylactic use to prevent thrombosis in patients with cardiovascular and cerebrovascular diseases owing to its ability to suppress the aggregation of platelets. It reaches its maximal blood concentration 1–2 h after being ingested, and after hydrolysis into salicylic acid in the liver, plasma, and red blood cells, is distributed in various tissue. In the gut, liver, and blood, salicylic acid is hydrolyzed rapidly into salicylate, which is then metabolized into salicyluric acid and glucuronide in the liver. Long-term exposure to high doses of aspirin, or a single overdose, particularly when the blood levels exceed 200 μg/ml, may result in adverse effects, especially in older individuals. With extremely high doses, highly conspicuous symptoms of overdose occur, such as nausea, vomiting, epigastric discomfort or pain, and other gastrointestinal responses (caused by direct irritation of the gastric mucosa; incidence at 3%–9%). Hepatic and renal impairment is common when blood aspirin levels exceed 250 μg/ml. Aspirin can penetrate the lipoprotein layer of the gastric mucosa, leading to mucosal erosion and counter diffusion of gastric acid, which ultimately enables the formation of ulcers and hemorrhage [1]. In this patient, the vomited bloody gastric content and several positive fecal occult blood findings could be attributed to this mechanism. Other adverse effects of aspirin include an antidiuretic effect [2,3] that can lead to chronic renal injury [4]. The patient in the present case presented with oliguria early in his hospitalization. Aspirin overdose can also lead to hyperglycemia and glucosuria, while producing hypoglycemia in diabetics, and can induce a negative nitrogen

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balance, decrease plasma phospholipid and cholesterol levels, and accelerate acetone body oxidation. Hyperglycemia and glucosuria in a patient without a history of diabetes suggests an adverse effect on the pancreas [5–7]. An infrequent adverse effect of aspirin overdose is liver impairment [8,9], which may be related to an allergic response or a direct toxic effect on hepatic cells. At a therapeutic dose, aspirin produces a slight hepatic impairment in ~10% of patients, although the incidence of obvious alanine aminotransferase (ALT) elevation is less than 2%. Aspirin overdose can lead to severe hepatic dysfunction and gallbladder impairments such as intrabiliary pressure elevation, mucosal congestion, exudation, and bile drainage obstruction. The slight ALT elevation and continuous increase in total, direct, and indirect serum bilirubin, as well as the yellowing of the patient’s skin and sclera, that were present 1 week after admission, indicated that our patient was suffering from obstructive jaundice. When dense bile or a stone is trapped in the duodenal ampulla, bacteria in infected bile can change conjugated bile acid into a free acid, which can activate pancreatic enzymes, resulting in biliary pancreatitis. In this patient, the bile withdrawn by PTCD was heavy and dark, and the sediments inside the bile duct were removed after the procedure, leading to an amelioration of the bile obstruction. Whether hepatic failure occurring more than a year after an aspirin overdose event could be a long-term adverse effect should be evaluated further [9]. Aspirin can also suppress myeloid blood cell production. There are numerous cases of blood cell abnormalities being caused by aspirin. Our patient showed pancytopenia at the time of his admission. Finally, aspirin overdose can result in an abnormal electroencephalopathy [10], acidbase disorder (respiratory alkalosis and metabolic acidosis), ketonuria, hyponatremia, hypopotassaemia, and proteinuria. The persistent acid-base disorder that the patient developed during his initial hospitalization may be related to this mechanism.

Compliance with ethics guidelines Zhuping Cao, Shiqi Liu, Jianhua Niu, Bing Wei, and Jie Xu declare that they have no conflict of interest. All clinical observation procedures performed were in accordance with the ethical standards of the responsible committee on human experimentation at the First Affiliated Hospital of Shihezi University and with the Helsinki Declaration of 1975, as revised in 2000.

References 1. García Rodríguez LA, Lin KJ, Hernández-Díaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation 2011; 123(10): 1108–1115

4 2. Thurlow W. Acetaminophen, aspirin, and renal failure. N Engl J Med 2002; 346(20): 1588–1589, author reply 1588–1589 3. Fored CM, Ejerblad E, Lindblad P, Fryzek JP, Dickman PW, Signorello LB, Lipworth L, Elinder CG, Blot WJ, McLaughlin JK, Zack MM, Nyrén O. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 2001; 345(25): 1801–1808 4. Evans M, Fored CM, Bellocco R, Fitzmaurice G, Fryzek JP, McLaughlin JK, Nyrén O, Elinder CG. Acetaminophen, aspirin and progression of advanced chronic kidney disease. Nephrol Dial Transplant 2009; 24(6): 1908–1918 5. Petersen HHH, Skovbjerg H. Acute pancreatitis—induced by 5aminosalicylic acid or an extraintestinal manifestation of ulcerative colitis? Ugeskr Laeger 1995; 157(39): 5400–5401 (in Danish) 6. Akyazi I, Eraslan E, Gülçubuk A, Ekiz EE, Cırakli ZL, Haktanir D, Bala DA, Ozkurt M, Matur E, Ozcan M. Long-term aspirin

Multiple organ dysfunction caused by aspirin overdose

7.

8.

9.

10.

pretreatment in the prevention of cerulein-induced acute pancreatitis in rats. World J Gastroenterol 2013; 19(19): 2894–2903 Antonopoulos S, Mikros S, Kokkoris S, Protopsaltis J, Filioti K, Karamanolis D, Giannoulis G. A case of acute pancreatitis possibly associated with combined salicylate and simvastatin treatment. JOP 2005; 6(3): 264–268 Hagiwara S, Kaneko M, Murata M, Ikegami T, Oshima K. A survival case of severe liver failure caused by acetylsalicylic acid that was treated with living donor liver transplantation. Hippokratia 2014; 18(1): 71–73 Lazarovits AI, Robinson GM, Devenyi P. Aspirin-induced hepatic encephalopathy and chronic liver disease. Ann Intern Med 1980; 93 (3): 510 Petty BG, Zahka KG, Bernstein MT. Aspirin hepatitis associated with encephalopathy. J Pediatr 1978; 93(5): 881–882

Severe hepatoxicity caused by aspirin overdose: a case report.

We report here the rare case of a 61-year-old man with multiple organ dysfunction caused by an aspirin overdose (4 g orally). The patient presented wi...
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