Pediatric Baclofen Overdose


A 16 year-old male presented to the emergency department after intentional overdose of 200 mg of baclofen. The patient was found in his bedroom by family members approximately 10 hours after ingestion with reported twitching, vomiting, unresponsiveness, and possible seizure activity. On arrival to the emergency department, the patient was awake, alert, and oriented; tearful, but otherwise asymptomatic.


Physical Exam

Vital signs included blood pressure 150/76, heart rate 112, temperature 99.2 F (37.3 C), respiratory rate 26, SpO2 97%. Physical exam showed frequent bilateral upper greater than lower extremity myoclonic jerks. The patient’s neurologic exam and physical exam were otherwise unremarkable.



The patient’s toxicological workup was pertinent for undetectable salicylate, acetaminophen, and ethanol levels. His urine drug screen was negative. EKG showed sinus tachycardia with normal QRS and QTc intervals. A head CT previously completed at an outside hospital was normal. The rest of his laboratory evaluation including CBC, electrolyte levels, and hepatic function tests, was unremarkable.



Baclofen is a centrally-acting skeletal muscle relaxant which functions as a GABA-B receptor agonist, believed to inhibit synaptic transmission of signals to the muscle from the spinal cord. Baclofen is typically prescribed for symptoms related to severe muscle spasm, such as in spinal cord injury or chronic neurologic disease (e.g. multiple sclerosis.) The medication can be administered either orally, or via an intrathecal pump.

Baclofen is absorbed rapidly from the GI tract in a dose-dependent manner, with peak serum levels occurring after ~1 hour (with a range of 0.5-4 hours). However, this has been found to be highly variable in pediatric patients. Its volume of distribution is also highly variable among pediatric patients, with nearly 50% interindividual variability. The reason for this variability is not clearly understood.

Baclofen is primarily excreted renally, with a serum half-life of 4.5 hours in pediatric patients, and a CSF half-life of 1.5 hours in intrathecal administration.

Baclofen overdose typically manifests with neurologic symptoms and dysautonomia. Symptoms are variable and may include: CNS depression/coma, hypotonia, hyporeflexia, seizure, respiratory depression, tachycardia, bradycardia, hypertension, hypotension, and arrhythmia. In adults, ingestions of >200 mg appear to correlate with an increased risk of respiratory failure, mechanical ventilation requirement, and ICU admission time.

 In an unfortunate case series, a group of teenagers overdosed on 60-600 mg of baclofen for recreational purposes. Patients displayed symptoms of overdose in 1-2 hours. 9 of 14 were intubated. Of 8 that were followed longitudinally: 7 were comatose, 6 were hypothermic, 5 were bradycardic, 4 were hypertensive, 8 were hyporeflexic, 3 had PVCs, and 2 had tonic-clonic seizures. The mean time of intubation was 40 hours. All patients recovered.



Treatment of baclofen overdose is primarily supportive with IV fluids, hemodynamic and respiratory support, and antiepileptics as needed. Activated charcoal may also be considered. There are case reports of physostigmine being effective in low/moderate overdoses; however, its use is controversial. Finally, hemodialysis does shorten clearance time and resolution of toxicity in patients with normal and impaired renal function.



Patients should be monitored until symptoms resolve. Depending on the dose ingested, the length of time since ingestion, clinical status, and laboratory analysis, they may be monitored either on the floor with telemetry or in the ICU.



The patient was treated with a 1 liter normal saline bolus and 1 mg of lorazepam IV; his hemodynamics normalized, his myoclonic twitching resolved, and he remained stable without seizure or complication throughout emergency department stay. He was admitted to the pediatric ICU for overnight monitoring, where he remained asymptomatic and had normal vital signs. The patient was then transferred to inpatient psychiatry for mental health treatment.



Baclofen overdoses typically present with a combination of altered mental status and or seizure, hypotonia, and dysautonomia. Treatment is primarily supportive and most patients recover with IV fluids, hemodynamic and respiratory support, and antiepileptics as-needed (usually benzodiazepines.) Activated charcoal should be considered. Patients should be admitted either to medical floor with telemetry or ICU depending on clinical status; they should remain admitted until symptoms resolve (typically several days, depending on ingested dose).

Faculty Reviewer: Dr. Jane Preotle 










Acetaminophen, Acetylcysteine, and Anaphylaxis With a Twist


A 15 year-old male, with a past medical history of intermittent asthma, presents with a chief complaint of diffuse abdominal pain, nausea, and two episodes of non-bloody, non-bilious emesis. His symptoms began five hours prior to arrival, and are not accompanied by diarrhea, constipation, genitourinary, urologic, or musculoskeletal symptoms. He provides limited history and appears tearful. On direct questioning, he endorses that he attempted suicide the night prior by taking a “handful of ibuprofen.” He does not know the exact number of pills, but estimates somewhere between 50 and 100, and does not know the dose strength. His mother, a clinical pharmacist, believes they were 200 mg tablets, and that there were no other pills in the house. The patient endorses feelings of depression in the prior month, and blames himself for his father having fallen off a roof (without injury) two years prior. He attends high school and is up-to-date on his vaccinations. He is a non-smoker, does not use alcohol, and endorses occasional marijuana use.  His only medication is an albuterol inhaler as needed.

Physical Exam

Initial vital signs: BP 122/82, HR 68 BPM, Temp 98.6 F, RR 20, and SpO2 100% on room air. Physical exam is notable for RUQ and LUQ tenderness without peritoneal signs. There are no scars or superficial cuts. He is tearful, but alert and oriented to person, place, and time.

Results and Management

The patient was placed on a cardiorespiratory monitor. Workup consisted of an EKG plus typical toxicologic labs, and consultation from poison control.

His EKG showed normal intervals and aVR morphology. Labs were notable for an acetaminophen level of 27 ug/mL and a slight elevation in transaminases, with AST 56 IU/L, and ALT 62 IU/L. On further questioning, the patient confessed that multiple types of pills were taken. Ingestion occurred at 2:00 AM, 14 hours prior to arrival. Given the poor history and elevated acetaminophen level, treatment based on the Rumack-Matthew nomogram (Figure 1) was felt to be beneficial.

Figure 1: Rumack-Matthew nomogram for acetaminophen ingestion.

Figure 1: Rumack-Matthew nomogram for acetaminophen ingestion.

The patient’s mother was concerned about his history of asthma, and her knowledge that NAC can cause bronchospasm; however, the benefits of treatment were felt to outweigh the risks. He was started on a standard 21-hour protocol, with a loading dose followed by two tapering doses.

Approximately one hour after the initial loading dose, the patient began to experience wheezing, a diffuse urticarial rash over the face, neck, shoulders, and thorax, and oral angioedema. He also became tachycardic. Given concern for a severe allergic reaction, bronchospasm, and possibly anaphylaxis, the infusion of NAC was held and he was treated with nebulized albuterol, IV diphenhydramine, IM epinephrine, IV normal saline, and IV corticosteroids. He was monitored in the emergency department for three hours, although his reaction resolved within 30 minutes.

Disposition and Resolution

The decision to restart NAC was considered, weighing the risk of possible anaphylaxis against the benefit of NAC to minimize potential hepatic insult. Given the low acetaminophen level, a repeat drug level and hepatic function panel were sent to inform this decision. These repeat labs came back with an undetectable acetaminophen level (now at 15 hours post-ingestion) and unchanged transaminase levels. NAC was not restarted on the basis of presumed completion of metabolism. The patient was admitted to the pediatric intensive care unit for monitoring, serial drug levels, and hepatic function panels. No further treatment was required during hospitalization. He was transferred to the psychiatry service on hospital day three for inpatient management of suicidal ideation and major depressive disorder. He did well with therapy and was discharged.

Case Discussion

This case illustrates elements of toxicity from two common over-the-counter medications, complicated by an adverse reaction to a life-saving treatment. Acetaminophen toxicity is a common emergency department phenomenon, and while ibuprofen is generally well-tolerated, it can cause toxicity at high doses.

Acetaminophen is metabolized by the liver via two pathways. First, conjugation to sulfate or glucuronide, which generates non-toxic metabolites, and second, via the CYP450 system, which generates a toxic free-radical metabolite, N-acetyl-P-benzoquinone (NAPQI).  NAPQI is neutralized by glutathione (Figure 2).

Figure 2: Acetaminophen metabolism.

Figure 2: Acetaminophen metabolism.


When acetaminophen is consumed in toxic doses, the pathways leading to nontoxic metabolites are overwhelmed and the accumulation of NAPQI depletes glutathione. In turn, the liver is unable to eliminate free oxygen radicals via glutathione, resulting in oxidative damage and mild, moderate, or fulminant liver failure if glutathione is not regenerated.

Patients are typically asymptomatic until 24-48 hours after an acute ingestion. Single doses over 150-200 mg/kg in healthy children pose significant risk of hepatotoxicity. Symptoms initially are nonspecific, with nausea, vomiting, and malaise, and can progress over a course of days to weeks to liver failure, recovery, or death. Treatment depends on the level of ingestion, the time from ingestion, and the presence of hepatic damage, but generally consists of gastric decontamination within the first hour after ingestion, oral or intravenous NAC, and supportive care. [1]

Ibuprofen, a non-steroidal anti-inflammatory drug, acts on cyclooxygenase enzymes to prevent conversion of arachidonic acid to prostaglandins and thromboxane, disrupting the gastric mucosal barrier and renal blood flow. At toxic doses, it can cause nausea, abdominal pain, gastritis, and renal failure. In severe presentations, acidosis and electrolyte disturbances are seen. The therapeutic window of ibuprofen is broad; toxicity typically does not occur until doses reach the 200-400 mg/kg range. Even in such cases, it is often mild and self-resolving with supportive care. The patient in this case likely consumed less than 100-200 mg/kg, which is unlikely to cause significant symptoms. His nausea, vomiting, malaise, and abdominal pain were likely secondary to gastric irritation from both ingestions in the early phase. [2]

NAC can be given orally or intravenously to manage acetaminophen overdose. Considerations for route depend on the severity of presentation and patient tolerance to PO medications. The duration of treatment varies by route. With IV, which was chosen for our patient due to poor PO tolerance and limited clarity around the time and quantity of ingestion, a loading dose (150 mg/kg administered over one hour) is then followed by tapered IV infusions over the next twenty hours (50 mg/kg administered over four hours, and 100 mg/kg administered over sixteen hours).

Unfortunately, NAC administration can be complicated by anaphylactoid reactions. These reactions are commonly limited to cutaneous symptoms of flushing and pruritus, with bronchospasm, angioedema, and shock occurring in <2% of patients. [3] Yarema and colleagues found in 2018 that 75.4% of anaphylactoid reactions to NAC fall within the cutaneous category. Of the total reactions observed, 95.4% of them occurred within the first five hours of treatment, which correlates with the delivery of high concentrations of drug. Female gender was associated with a more severe reaction, while higher serum acetaminophen concentrations were associated with less severe reactions. [4]

Pakravan et al further researched the mechanism of this reaction in 2008. They found that levels of serum histamine correlated with reaction severity, but that regardless of severity, there was no increase in serum tryptase or inflammatory cytokines. This suggests a non-mast-cell source of histamine and thus, a non-IgE-mediated reaction. This distinguishes the reaction from true anaphylaxis, however, the final common histaminergic pathways are similar, making clinical differentiation nearly impossible and arguments for different treatments in the initial stage largely academic. [5]

The pathophysiology of anaphylaxis and anaphylactoid reactions stems from the effect of histamine on vascular and bronchial smooth muscle leading to cutaneous vasodilation and third-spacing (hives, rash, pruritis), bronchospasm (wheezing), and reduced systemic vascular resistance (tachycardia, hypotension). Reversing this pathophysiology and providing supportive care is accomplished through intramuscular epinephrine (increases systemic vascular resistance and decreases bronchoconstriction), intravenous H1/H2 blockers (decreases vasodilation and third-spacing), nebulized beta-agonists (relieves bronchospasm), intravenous glucocorticoids (anti-inflammatory), and intravenous fluids (intravascular resuscitation, increases cardiac output). [7]

Yamamoto et al researched the frequency of occurrence as related to the treatment timeline, finding that the reaction will most commonly occur during the initial loading dose (61%), that a smaller fraction will occur over the next four hours (37%), and that the least frequent fraction occurs during the terminal taper (2%). [6]

Regardless, this anaphylactoid reaction prompts considerations about appropriate treatment and, if stopped, how and whether or not to restart the drug. The reaction itself, even when severe, typically does not necessitate cessation of therapy. A common approach to managing the reaction includes temporarily holding the infusion, initiating the normal anaphylactic countermeasures, then restarting the infusion at half of the previous rate after symptom control. Generally, the ongoing infusion is well-tolerated once histaminergic blockade is in place. This off-target effect has no effect on the critical reaction of regenerating hepatic glutathione stores. NAC is very effective at preventing fulminant hepatic failure, even in severe cases of overdose, and restarting treatment should be a high priority.

In this case, the patient’s parents refused to restart the medication given his severe reaction. He had not been previously exposed to NAC, which suggests that his reaction was likely anaphylactoid as opposed to anaphylaxis. His acetaminophen level at 14 hours had scored onto the lowest acceptable treatment line on the Rumack-Matthew nomogram and his liver function was only notable for a minimal-mild elevation in transaminases. Given the lower concern for severe toxicity, and repeat labs demonstrating an undetectable acetaminophen level with no appreciable change in hepatic function, the parents and treatment team were comfortable without restarting it in this case.

Lastly, an additional complication of NAC relates to coagulopathy. Sandilands et al reported elevations in INR in association with NAC treatment; however, an initial rise in INR, assuming it stabilizes, is not indicative of progressive liver failure. Elevations typically stabilize around an INR of 1.3, which is not concerning for increased risk of bleeding. [8]

In summary, treatment with NAC may be complicated by histamine-mediated anaphylactoid reactions, which are commonly limited to cutaneous reactions easily treated with histamine antagonists. Severe reactions may necessitate adjunct treatment from inhaled or intravenous beta-agonists, intramuscular beta-agonists, intravenous glucocorticoids, and fluids. True anaphylaxis requires previous sensitization. Unless extenuating circumstances or clinical context exist, NAC should be restarted after treating the reaction. Elevations in INR are common and do not imply liver failure unless they continue to rise.


Faculty Reviewer: Dr. Jane Preotle


  1. Farrell SE, Miller MA. Acetaminophen Toxicity. Wolters Klewer, eMedicine. Updated 22 Jan 2018. Accessed 24 Sep 2018.

  2. Wiegand TJ, Schlamovitz GZ. Nonsteroidal Anti-inflammatory Drug Toxicity. Wolters Klewer, eMedicine. Updated 20 Dec 2017. Accessed 16 Sep 2018.

  3. Blackford MG, Felter T, Gothard MD, Reed MD. Assessment of the clinical use of IV and oral NAC in the treatment of acute acetaminophen poisoning in children: a retrospective review. Clin Ther.  2011; 33(9):1322-30 (ISSN: 1879-114X)

  4. Yarema M, Chopra P, Sivilotti MLA, et. Al. Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning. J Med Toxicol. 2018 Jun;14(2):120-127. Doi: 10.1007/s13181-018-0653-9.

  5. Pakravan N, Waring WS, Sharma S et. Al. Risk Factors and Mechanisms of Anaphylactoid Reactions to Acetylcysteine in Acetaminophen Overdose. J Clin Tox 2008 Jun;46:697-702.

  6. Yamamoto T, Spencer T, Dargan PL, Wood DM. Incidence and management of N-acetylcysteine-related anaphylactoid reactions during the management of acute paracetamol overdose. Eur J Emerg Med. 2014 Feb;21(1):57-60. doi: 10.1097/MEJ.0b013e328364eb22.

  7. Bailey B, McGuigan MA. Management of Anaphylactoid reactions to IV N-acetylcysteine. Ann Emerg Med. 1998 Jun;31(6):710-5.

  8. Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila). 2009 Feb;47(2):81-8.

Acetaminophen: Where is it Found? And How to Handle Too Much of It!


A 14-year-old girl with a history of suicidal behavior presents to a pediatric emergency department with polysubstance ingestion.  Over the last two days she has ingested variable amounts of lorazepam, alcohol, and DayQuil™ (acetaminophen, dextromethorphan, and phenylephrine).  She drank an unknown quantity of DayQuil™ the day prior and admits to drinking an entire bottle on the day of presentation.  The patient denies any current symptoms.

Vital signs:  T 97.9 F, BP 133/83, HR 114, RR 20, SpO2 100%

On examination, she is in no acute distress.  Her neurologic examination is non-focal with a Glasgow Coma Scale of 15.  Her abdomen is benign.  She has linear scars to the left forearm from self-injurious behavior.  She is cooperative, nonchalant about her ingestion, describes her mood as “numb”, and has a flat affect. 

Her laboratory analyses reveal an acetaminophen level of 65 mcg/mL.  Liver function tests are unremarkable, INR is 1.0, and ethanol is zero.  All other diagnostics are unremarkable.  Treatment is initiated, and she is admitted to Pediatrics for acetaminophen overdose.  


Acetaminophen, commonly referred to internationally as paracetamol, is one of the most widely used analgesics and antipyretics.  It is a major component of many over-the-counter and prescription medications (Table 1).  Each year, approximately 30,000 patients are hospitalized in the United States for acetaminophen toxicity, with half of overdoses thought to be intentional. (1)  Intentional pediatric ingestions typically occur in adolescents while unintentional ingestions are more common among younger children. (2)  The therapeutic dose in children is 15 mg/kg  every four to six hours.  The minimum toxic dose for an acute ingestion is 150 mg/kg. (3,4)  In chronic overdose, the minimum toxic threshold is 150-175 mg/kg over two to four days. (3,5)  

Table 1: Common Medications Containing Acetaminophen
Alka-Seltzer Plus ® NORCO® Sudafed®
Dayquil® Nyquil® Theraflu®
Excedrin® Paracetamol Tylenol® Brand Products
Hydrocet® Percocet® Vicks®
Lortab® Robitussin® Vicodin®
Mucinex® Singlet®

The clinical manifestations of acute acetaminophen poisoning in children are nonspecific.  Initially, patients may be asymptomatic or have mild symptoms such as nausea and vomiting.  Liver injury can occur after approximately 24 hours and manifest as right upper quadrant pain or tenderness, vomiting, jaundice, and elevations in transaminases and prothrombin time.  At peak liver injury, patients can present with signs of fulminant liver failure such as hepatic encephalopathy, systemic inflammatory response system, hypotension, and death. (6)

All patients in whom acetaminophen toxicity is suspected should have a serum acetaminophen concentration drawn.  In patient with a single acute ingestion, the time of ingestion should be established, as a serum acetaminophen concentration at four hours post-ingestion will determine the need for antidotal therapy with N-acetylcysteine (NAC).  The four-hour concentration should be plotted against the treatment nomogram, and concentrations in the probable hepatic toxicity range should be treated with NAC. (4,6,7)

Figure        SEQ Figure \* ARABIC     1      . Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (      ADDIN EN.CITE
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control&lt;/keyword&gt;&lt;keyword&gt;Cysteamine/therapeutic use&lt;/keyword&gt;&lt;keyword&gt;Humans&lt;/keyword&gt;&lt;keyword&gt;Hypoglycemia/chemically
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Figure 1. Treatment Nomogram for Acetaminophen Toxicity, Reproduced from Rumack et. al 1975 (7)

In chronic ingestions, the treatment nomogram cannot be used.  Laboratory testing for serum acetaminophen concentration and liver function should be obtained for any at-risk patient.  Patients with evidence of liver injury (AST greater than two times normal or greater than 120 IUL or those with serum acetaminophen levels greater than 30 mcg/mL should have antidotal therapy initiated. (5,6)

Gastric decontamination with activated charcoal is recommended in all pediatric patients who present within four hours of acetaminophen ingestion.  Contraindications include gastrointestinal obstruction or any altered mental status in which airway protection is a concern.  Endotracheal intubation should not be performed solely for the purpose of giving activated charcoal.  Activated charcoal has not been shown to reduce acetaminophen absorption when given greater than four hours after ingestion and is not recommended in this time frame.  Activated charcoal is given as a single dose of 1 g/kg by mouth (maximum 50 g). (8,9) 

Once the need for N-acetylcysteine antidotal therapy is determined, it should be given as soon as possible.  When given within 8 hours of ingestion, the mortality rate approaches 0; however, NAC may be beneficial up to 24 hours after ingestion.  NAC should be given intravenously (IV) if available; however, providers should be aware that IV NAC can cause severe anaphylactoid reactions.  Preparations should be made for immediate interventions if anaphylaxis occurs, and patients should be monitored closely during the initial 30 minutes of the infusion. (6,10)  Providers should also be aware that prothrombin time and INR can be artificially elevated by NAC, which can obscure signs of worsening liver function. (11) 

A well-established protocol for IV NAC dosing involves a 21-hour administration procedure detailed below.  Repeat acetaminophen levels, liver function tests, and INR should be repeated 9 hours into the protocol. (12,13)

Loading dose of 150 mg/kg IV (maximum 15,000 mg) in 200 mL dextrose 5% in water (D5W) infused over 60 minutes

Followed by

First maintenance dose of 50 mg/kg IV (maximum 5,000 mg) in 500 ml D5W infused over 4 hours

Followed by

Second maintenance dose of 100 mg/kg IV (maximum 10,000 mg) in 1000 mL D5W infused over 16 hours

Poor prognostic indicators for liver function include the King’s College Criteria.  Patients with acidosis with pH < 7.3 or patients with the combination of prothrombin time > 100 seconds and creatinine > 3.3 mg/dL and hepatic encephalopathy grade III – IV (marked confusion or coma) are considered high risk for fulminant liver failure and should be transferred to a liver transplant center. (14)


Given that the patient had an elevated acetaminophen level greater than 30 mcg/mL with multiple ingestions over the last 48 hours, she was treated with N-acetylcysteine.   Labs were rechecked at 19 hours after initiation of NAC.  Liver function tests and INR were stable.  Repeat acetaminophen level was < 10 mcg/mL.  She was ultimately discharged after Psychiatric evaluation with a home safety plan and outpatient Psychiatry follow up.

Faculty Reviewer: Dr. Jane Preotle


1.         Blieden M, Paramore LC, Shah D, Ben-Joseph R. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Rev Clin Pharmacol. 2014;7(3):341-348.

2.            Myers WC, Otto TA, Harris E, Diaco D, Moreno A. Acetaminophen overdose as a suicidal gesture: a survey of adolescents' knowledge of its potential for toxicity. J Am Acad Child Adolesc Psychiatry. 1992;31(4):686-690.

3.            Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017;25(1):1-9.

4.            Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen overdose. Clin Pharm. 1991;10(10):765-774.

5.            Sztajnkrycer MJ, Bond GR. Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Pediatr. 2001;13(2):177-182.

6.            Walls RM, Hockberger RS, Gausche-Hill M. Rosen's emergency medicine : concepts and clinical practice. In: Ninth edition. ed. Philadelphia, PA: Elsevier,; 2018: Full text available from ClinicalKey Flex.

7.            Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55(6):871-876.

8.            Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018;2:CD003328.

9.            Spiller HA, Krenzelok EP, Grande GA, Safir EF, Diamond JJ. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med. 1994;23(3):519-523.

10.          Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet. 2014;383(9918):697-704.

11.          Pizon AF, Jang DH, Wang HE. The in vitro effect of N-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med. 2011;18(4):351-354.

12.          Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977;2(8035):432-434.

13.          Yarema MC, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54(4):606-614.

14.          O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439-445.