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Year : 2015  |  Volume : 29  |  Issue : 1  |  Page : 52-54

Significantly raised alanine aminotransferase level following single dose of intravenous paracetamol in a healthy patient

Department of Anesthesia and ICU, Khoula Hospital, Muscat, Sultanate of Oman

Date of Web Publication1-Dec-2014

Correspondence Address:
Naresh Kaul
Department of Anesthesia and ICU, Khoula Hospital, Muscat, Sultanate of Oman

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-5333.145949

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A 12-year-old ASA I female patient underwent correction of posterior scoliosis of dorsolumbar spine under total intravenous anesthesia using a combination of remifentanil and propofol. Induced hypotension was maintained between 55 and 65 mmHg. Intraoperatively, patient received a single injection of 1.0 g paracetamol. Surgery lasted 6 h and 40 min and was essentially uneventful. A follow-up investigation in the intensive care unit 6 h after the surgery revealed alanine transaminase levels of 547 I/U. This increased to 924 I/U on the 2 nd postoperative day after the patient received 500 mg per-rectal paracetamol. Stopping administration of paracetamol restored alanine transaminase level to normal without needing N-acetylcysteine.

Keywords: Alanine N-acetylcysteine, hepatic toxicity, paracetamol

How to cite this article:
Khan RM, Nair S, Al-Kharusi AS, Aziz H, Kaul N. Significantly raised alanine aminotransferase level following single dose of intravenous paracetamol in a healthy patient. Indian J Pain 2015;29:52-4

How to cite this URL:
Khan RM, Nair S, Al-Kharusi AS, Aziz H, Kaul N. Significantly raised alanine aminotransferase level following single dose of intravenous paracetamol in a healthy patient. Indian J Pain [serial online] 2015 [cited 2021 Jan 28];29:52-4. Available from: https://www.indianjpain.org/text.asp?2015/29/1/52/145949

  Introduction Top

Paracetamol is often administered before or during surgery for a smooth transition to an effective postoperative analgesia. [1],[2] It is safe and rarely associated with hepatotoxicity when administered in the therapeutic range (up to 4 g daily). [3] We report a case where a single dose of intravenous paracetamol resulted in raised alanine aminotransferase (ALT) levels with a further rise after a second per-rectal dose.

  Case Report Top

A 12-year-old ASA I female patient weighing 52 Kg was scheduled for correction of posterior scoliosis of dorsolumbar spine. She had no known medical problems. Her Kobb's angle was 68°. Relevant laboratory investigations including liver function tests (LFT) were within normal limits.

Patient was premedicated with 3.75 mg midazolam orally 45 min prior to induction of anesthesia. Following preoxygenation, patient was induced with propofol (120 mg) and fentanyl 100 mg. Relaxation for tracheal intubation was achieved with 8.0 mg cisatracurium. Following tracheal intubation, anesthesia was maintained using total intravenous anesthesia with propofol (4-6 mg/kg/h) and remifentanil (20-25 mg/kg/h) titrated to keep mean arterial pressure between 55 and 60 mmHg. Patient was ventilated with a tidal volume of 450 ml using a mixture of oxygen and air (2 l/min each) with the rate adjusted to keep end-tidal carbon dioxide between 32 and 35 mmHg. A multilumen central venous line and an invasive arterial line were uneventfully placed. Besides routine monitoring, evoked potentials (somatosensory and motor) and electromyography were closely monitored. D2 to L2 levels were exposed by the operating spine surgeon and spine deformity corrected by putting monoaxial screws and bilateral rods. Intraoperatively, 3.5 l of Ringer lactate infusion and 3 units of packed blood cells were administered via fluid warmer. Estimated blood loss was 1200 ml. Total urine output during the intraoperative period was 700 ml. Intraoperatively, mean arterial pressure was maintained in the range of 48-65 mmHg, heart rate between 52 and 74/min and mid-esophageal temperature was noted to be around 36.2°C. Patient was administered 1 g of paracetamol intravenously after the commencement of anesthesia. Duration of surgery was 6 h and 40 min. Before surgical closure, an epidural catheter was placed by the operating surgeon via the surgical wound at T4 level and threaded 4 cm toward T1. Postoperative analgesia was provided by an infusion of 4-6 ml/h of a mixture of 0.1% bupivacaine and 2.0 mg/ml of fentanyl.

As per routine, 6 h postoperatively, follow-up investigations were ordered. ALT and bilirubin levels were noted to be 547 units/liter [U/L] (normal laboratory value 4-40 U/L] and 36.9 mmol/liter [mmol/L] (normal laboratory value 3.4-17.4 mmol/L) respectively. All other laboratory findings were within acceptable limits. It was decided to repeat the investigations after 6 h in view of abnormal LFT. When repeated, ALT and bilirubin levels were 762.0 U/L and 32.2 mmol/L respectively. Since no apparent cause was noted, it was decided to keep a close watch over LFT. The next morning, levels of bilirubin had come to within normal values, but ALT levels were still high (651.2 U/L). Other than mild pain, patient had no other complaints. It was decided not to increase the infusion rate of bupivacaine/fentanyl mixture as she had occasional bradycardia of <50 beats/min and her blood pressure were on the lower side of normal (systolic range 95-105 mm Hg, diastolic range 46-60 mmHg). To alleviate pain, patient was administered paracetamol suppository (500 mg) the same afternoon. The same evening, her ALT levels rose to 924.0 U/L while bilirubin values remained normal (14.3 mmol/L). It was now decided to withhold paracetamol as it was felt that this could be causing a rise in ALT levels. On the 3 rd postoperative day, her ALT level showed a downward trend and was recorded as 634.0 U/L and on the subsequent day as 183.96 U/L till it reached normal values on the 5 th postoperative day. Rest of her recovery period was uneventful and she was discharged on the 8 th postoperative day.

  Discussion Top

Paracetamol is one of the most commonly used drugs for relieving mild to moderate pain. [4] In addition, it has an opioid sparing effect [5] and has been employed to achieve 20-30% reduction in narcotic requirement. [6] Keeping this in mind, we administered 1 g paracetamol intravenously to reduce intraoperative requirement of remifentanil in our patient. Intraoperative period was largely uneventful. However, there were periods where the patient's mean arterial pressure dropped below 50 mmHg. These periods were short and usually lasted <5-6 min and were quickly addressed by reducing propofol and/or remifentanil infusion rate.

Ture et al. have studied the effect of propofol infusion on hepatic function in children. [7] They noted an increase in ALT levels that returned to normal within a week's time. On the other hand, remifentanil is considered safe during total intravenous anesthesia for any adverse effects on LFT. [8]

Liver injury from paracetamol is rare in children. [9] Aminotransferases levels may rise when administered as 4.0 g/day over a period of time [10] or as an accidental or suicidal ingestion of a large dose of paracetamol. [11],[12] Raised levels of ALT in our patient in the early postoperative period were unexpected and could not be attributed to any known cause. At the initial stages, paracetamol administration was not considered as a cause of abnormal LFT as the patient had also received propofol. However, further elevation after per-rectal dose of paracetamol nearly 30 h later helped us to zero on paracetamol as the etiological factor. On the contrary, raised serum bilirubin level was thought to be due to absorbed hematoma and/or some lysed red blood cells in the transfused packs.

There is a report in the literature of a 7-year-old girl developing toxic epidermal necrolysis with raised ALT levels after just three doses of paracetamol. [13] However, our patient developed raised ALT level after a single dose which was aggravated by the administration of a second dose. Shinzawa et al. [14] drew attention to an allergic reaction in response to paracetamol therapy lasting a few days. We could not rule out this possibility as we did not have the facility for lymphocyte stimulation test to paracetamol. Our patient tested negative for all forms of infective hepatitis.

We did not use N-acetylcysteine as therapeutic intervention for paracetamol toxicity as ALT levels started normalizing on discontinuing it after its second dose.

This case report highlights the possibility of paracetamol-induced liver toxicity even with a single dose, a finding not yet described in the literature. What role could induce hypotension have played in our patient to enhance adverse hepatic effect of paracetamol is not clear. We would recommend caution and estimation of ALT levels in the early postoperative period in patients undergoing prolong period of induced hypotension and receiving paracetamol. This would enable an early diagnosis of any adverse hepatic effects before damage becomes serious and irreversible.

  References Top

Dahl JB, Møiniche S. Pre-emptive analgesia. Br Med Bull 2004;71:13-27.  Back to cited text no. 1
Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: A meta-analysis. Anesth Analg 2005;100:757-73.  Back to cited text no. 2
Gregoire N, Hovsepian L, Gualano V, Evene E, Dufour G, Gendron A. Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clin Pharmacol Ther 2007;81:401-5.  Back to cited text no. 3
Kehlet H, Werner MU. Role of paracetamol in the acute pain management. Drugs 2003;63:15-22.  Back to cited text no. 4
Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth 2013;23:475-95.  Back to cited text no. 5
Cobby TF, Crighton IM, Kyriakides K, Hobbs GJ. Rectal paracetamol has a significant morphine-sparing effect after hysterectomy. Br J Anaesth 1999;83:253-6.  Back to cited text no. 6
Türe H, Mercan A, Koner O, Aykac B, Türe U. The effects of propofol infusion on hepatic and pancreatic function and acid-base status in children undergoing craniotomy and receiving phenytoin. Anesth Analg 2009;109:366-71.  Back to cited text no. 7
Mizrak A. Remifentanil and fentanyl use and the liver function tests. J Clin Anal Med 2012;3:7-10.  Back to cited text no. 8
Kozer E, Greenberg R, Zimmerman DR, Berkovitch M. Repeated supratherapeutic doses of paracetamol in children - a literature review and suggested clinical approach. Acta Paediatr 2006;95:1165-71.  Back to cited text no. 9
Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: A randomized controlled trial. JAMA 2006;296:87-93.  Back to cited text no. 10
Schiødt FV, Rochling FA, Casey DL, Lee WM. Acetaminophen toxicity in an urban county hospital. N Engl J Med 1997;337:1112-7.  Back to cited text no. 11
Farooqi VA, Khokhar N. Paracetamol poisoning resulting in massively raised serum transaminases. J Pak Med Assoc 2001;51:303-4.  Back to cited text no. 12
Halevi A, Ben-Amitai D, Garty BZ. Toxic epidermal necrolysis associated with acetaminophen ingestion. Ann Pharmacother 2000;34:32-4.  Back to cited text no. 13
Shinzawa H, Togashi H, Sugahara K, Ishibashi M, Terui Y, Aoki M, et al. Acute cholestatic hepatitis caused by a probable allergic reaction to paracetamol in an adolescent. Tohoku J Exp Med 2001;193:255-8.  Back to cited text no. 14


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