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Introduction: N-acetylcysteine (NAC) administration is recommended to all patients judged to be at risk of developing hepatotoxicity following paracetamol overdose. However, it has been shown that standard i.v. dosing can cause symptomatic hyponatraemia in children. We describe a case series using 0.45% NaCl plus 5% dextrose for infusing i.v. NAC in children with paracetamol poisoning.

Objective Paracetamol overdose is a common presentation to UK emergency departments, and national audits consistently identify shortfalls in the management of these patients. This study assesses the potential of a web-based computer application to improve the assessment and treatment of these patients. Methods A retrospective cohort of patients was identified and their actual management and that advised by the software were assessed against current guidelines. Results The application gave correct advice in all cases, significantly outperforming both actual treatment when the patients originally presented, and national performance based on previous College of Emergency Medicine audits. Conclusions Advice from custom-written software outperforms actual treatment of patients presenting after paracetamol overdose.

In 1998 the United Kingdom limited the availability of paracetamol sold over-the-counter in an effort to reduce serious paracetamol overdose. Since that time debate has continued on the effectiveness of this policy in reducing what is acknowledged as a major public health problem. This commentary reviews recent publications on this topic which suggest that the effects were small. Reasons for this are discussed using data from recent work.

A short-cut review was carried out to establish whether oral N-acetylcysteine is as effective as intravenous N-acetylcysteine in the management of paracetamol overdose. Seven studies were directly relevant to the question. The author, year and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that oral N-acetylcysteine is a safe alternative in patients for whom the intravenous route is not an option.

A modified-release formulation of paracetamol is currently available in Australasia and marketed under a number of different trade names. These include: Panadol Osteo, Panadol Extend Tablets, and Duatrol SR. We report four cases of intentional overdose with this formulation resulting in delay to peak plasma paracetamol concentrations and prolonged paracetamol absorption. Physicians must be aware that a single plasma paracetamol estimation four or more hours post-ingestion may not be adequate in the risk assessment of patients requiring treatment with N-acetylcysteine (NAC). Current Australasian guidelines for the management of modified-release paracetamol overdose advise empiric commencement of NAC if the suspected ingested dose is greater than 10 grams or 200 mg/kg (whichever is the least), an initial plasma paracetamol concentration should be assayed four or more hours post-ingestion and a second assay should be estimated four hours after the first. Treatment with NAC should continue if either concentration falls above the paracetamol treatment nomogram line. With massive ingestions of this paracetamol formulation (>50 grams) plasma concentrations may be elevated for several days and prolonged treatment with NAC is recommended. When modified-release paracetamol overdose is suspected a clinical toxicologist or Poisons Information Centre should be consulted to help guide management decisions.

IntroductionParacetamol is the most commonly used drug in deliberate poisoning. N-acetylcysteine is the standard antidote for significant acute paracetamol overdose, but the route of administration varies between countries. This review aimed to find and appraise those comparative studies which would help answer the following question: in patients who have taken an overdose of paracetamol requiring antidote, is there any difference between intravenous and oral N-acetylcysteine in mortality, hepatotoxicity, adverse drug reactions or cost?MethodsA literature search was conducted using Medline and other databases. Relevant papers were identified and appraised.ResultsOne animal study and seven comparative clinical studies were identified and appraised. The quality of the evidence was generally poor, and there was no clear difference in outcomes between the two routes of administration.ConclusionsWithout evidence of advantage for one route over the other, routine practice should not be changed. However, after 30 years experience, both routes appear to be effective and safe, and in countries where intravenous administration is the standard, it would be reasonable to consider the oral route as an alternative when intravenous access is problematic. There is a need for prospective, randomised trials to determine the relative effectiveness, safety and cost of intravenous and oral formulations of N-acetylcysteine.

Two cases of unintentional paracetamol overdose are presented. Over a one month period these patients presented to an Accident and Emergency (A&E) department with symptoms of paracetamol toxicity, following the ingestion of large quantities of analgesia for the self treatment of dental pain. In one case the patient had no access to a dentist. Both patients required admission under the care of the medical on-call team and required anti-toxicity treatment to prevent permanent liver injury. Subsequent referrals were made to the oral and maxillofacial surgery team who provided emergency dental treatment and advice on further dental care. This paper highlights the significant signs and symptoms of paracetamol overdose about which dental practitioners should be aware. It also describes the management principles required to prevent potentially life threatening liver damage. Discussion is also made of the potential impact on patients struggling to cope with pulpal pain without access to a general dental practitioner.

We read with interest the letter by Riggan et al. We agree that the Rumack-Matthew Nomogram is not applicable for common scenarios such as supratherapeutic ingestions, nor does it predict the devel...

Introduction There have been documented cases of serious and life-threatening health effects due to patients taking unintentional analgesia overdose secondary to dental pain. We aimed to determine firstly what proportion of unintentional paracetamol overdose cases admitted to an acute medical assessment unit (MAU) were secondary to dental pain, secondly what proportion of such cases encountered barriers to accessing emergency dental care and finally what clinical burden such cases placed on the hospital services. Method The clinical coding department provided information to allow appropriate identification and data collection from patient discharge summaries and case notes of all unintentional paracetamol overdose cases secondary to dental pain over a 24 month period (1 March 2012 to 28 February 2014). Results One hundred and sixteen admissions were identified specifically for unintentional paracetamol overdose. Dental pain accounted for 48 (41%) of all cases. Females (67%) were twice as likely to be admitted, compared to males (33%), with a mean age of 36 years and four months. Thirty-two (63%) non-dentally registered and all nine (100%) registered patients were unable to access timely emergency dental care before their admission. Forty cases (83%) were referred to the hospital oral and maxillofacial services (OMFS). Thirty-seven (93%) patients underwent elective outpatient dental extractions and the remaining three (7%) patients were admitted for intravenous antibiotics, incision and drainage and dental extractions. All patients were treated under local anaesthetic. Conclusion Dental pain is the single most common cause of acute medical admission secondary to unintentional paracetamol overdose. Patients registered with a general dental practitioner (GDP), as well as those not registered with a GDP, had difficulty accessing timely emergency primary dental care.

OBJECTIVES: To evaluate the failure rate of the 150-treatment line for paracetamol overdose in Hong Kong, and the impact if the treatment threshold was lowered. SETTING: Public hospitals, Hong Kong. PATIENTS: All patients with acute paracetamol overdose reported to the Hong Kong Poison Information Centre from 1 January 2011 to 31 December 2013 were studied and analysed for the timed serum paracetamol concentration and their relationship to different treatment lines. Presence of significant liver injury following paracetamol overdose was documented. The potential financial burden of different treatment lines implemented locally was estimated. RESULTS: Of 893 patients, there were 187 (20.9%) with serum paracetamol concentration above the 150-treatment line; 112 (12.5%) had serum paracetamol concentration between the 100- and 150-treatment lines, and 594 (66.5%) had serum paracetamol level below the 100-treatment line. Of the 25 (2.8%) patients who developed significant liver injury, two were between the 100- and 150-treatment lines, and the other two were below the 100-treatment line. The failure rate of the 150-treatment line was 0.45%. Lowering the treatment threshold to the 100-treatment line might lower the failure rate of the treatment nomogram to 0.22% but approximately 37 more patients per year would need to be treated. It would incur an additional annual cost of HK$189 131, and an additional 1.83 anaphylactoid reactions per year. The number needed-to-treat to potentially reduce one significant liver injury is 112. CONCLUSIONS: Lowering the treatment threshold of paracetamol overdose may reduce the treatment-line failure rate. Nonetheless such a decision must be balanced against the excess in treatment complications and health care resources. Language: en

The diagnosis of drug-induced liver injury (DILI) is largely a diagnosis of exclusion because, with the possible exception of protein:drug adducts in paracetamol overdose, there are no laboratory, biopsy or imaging tests that alone are capable of establishing an unequivocal diagnosis of DILI. However, it is increasingly appreciated that drugs that cause DILI typically have characteristic clinical presentations or ‘signatures' that can be very useful in the diagnosis of DILI. Indeed, knowing a drug's DILI signature (or sometimes signatures) and the incidence rate of DILI during treatment with that drug are perhaps the most useful pieces of historical information in arriving at the diagnosis of DILI. Components of the signature include the typical latency from the onset of treatment, whether there are extrahepatic manifestations, whether the injury is hepatocellular, cholestatic or mixed, and sometimes characteristic features on biopsy or serological testing (e.g. liver autoantibodies). A major advance has been the establishment of the LiverTox website (http://livertox.nih.gov/) which provides open access to standardized entries for over 600 different drugs, including the characteristic clinical presentations of DILI when known. LiverTox will also calculate the causality score for individual cases using the RUCAM instrument and case-specific data entered by the site user. However, the problem with standard diagnostic instruments such as the RUCAM is that DILI signatures are not incorporated into the scoring system. The person entering data must therefore subjectively weigh the RUCAM score with the characteristic DILI signature(s) of the drug to arrive at a diagnosis. In the future, it should be possible to construct improved diagnostic instruments that objectively incorporate DILI signatures, data-based estimates of the incidence rates of DILI from each implicated drug, and perhaps genetic variants associated with the risk of DILI.

To the Editor: We are grateful for Professor Bateman's interest and insightful comments. We fully agree that the ongoing assessment of a patient with hepatotoxicity following paracetamol overdose s...

A 29-year-old, 65 kg, Chinese man presented to hospital 10 hours after ingesting 30 g of paracetamol (462 mg/kg body weight). The blood paracetamol level was 145 µg/ml at 10 hours post-ingestion. He had no known risk factors for hepatotoxicity and was treated with intravenous N-acetylcysteine (NAC). Serum creatinine level rose to a maximum of 455 µmol/L on day 8; it gradually declined without the need for dialysis. Little is known of the risk factors for nephrotoxicity, which may occur with or without concurrent liver damage, suggesting possible primary toxic effects on the kidney. The use of NAC in this case may have prevented the progression to liver failure and reduced the severity of the nephrotoxic effects.

Fulminant hepatic encephalopathy has a high mortality. This case report describes the role of cerebral microdialysis as an adjunct to the management of a 49-year-old woman with hepatic encephalopathy secondary to a paracetamol overdose. The application of the microdialysis technique, by detecting a very low cerebral glucose concentration in the presence of a normal plasma glucose, assisted in clinical decision making. Cerebral microdialysis, by enabling continuous on-line monitoring of substrate delivery and metabolism, may have a role in the management of patients with fulminant hepatic failure.

Pharmacology 2013; a meeting of the British Pharmacological Society Queen Elizabeth II Conference Centre, Westminster, London, UK, 17–19 December 2013 Pharmacology 2013 is the annual meeting of the British Pharmacological Society, and was held on 17–19th December 2013 at the Queen Elizabeth II Conference Centre in Westminster, London. This report will discuss the symposium entitled ‘Paracetamol poisoning in the United Kingdom – where are we now and what is the future?’ Paracetamol overdose is a common and important presentation to emergency departments. This symposium and report aim to highlight current practice legislation surrounding the purchase of paracetamol and its compounds, and novel biomarkers for the diagnosis and identification of high-risk groups who require efficient instigation of treatment.

Summary Background: Pack sizes of paracetamol available to the public were reduced by legislation in 1998. Objective: To study the effect of the legislation on paracetamol poisoning related admissions to an accident and emergency department and to a tertiary referral liver unit. Method: Data were obtained from the University Hospitals, Birmingham, UK (UHB) Trust Information Service and the Queen Elizabeth Hospital liver unit records on (a) the number of patients admitted to hospital because of paracetamol overdose and (b) the number of patients admitted to the liver unit with parcetamol-induced hepatotoxicity. Results: Prior to legislation, an average of 360 people a year were admitted to UHB. However, following the change in legislation the number of admissions has fallen to an average of 250 people per year. This represents a reduction of 31%. Prior to legislation, an average of 76 people per year were admitted to the liver unit. Post-legislation this number has dropped to an average of 38 per year representing a reduction of 50%. Conclusion: Legislation restricting paracetamol pack-size reduced the incidence and severity of poisoning.

While on a clinical shift in the emergency department you attend to a 24-year-old female who has taken a clinically significant paracetamol overdose and requires N-acetylcysteine (NAC), you are wondering if a reduction in infusion rate of NAC will reduce adverse side effects such as vomiting and nausea? In an adult who has taken an acute clinically significant paracetamol overdose requiring treatment, does reducing the rate of the initial dose of NAC reduce adverse effects? Ovid MEDLINE 1946 to present. Embase 1974 to 10 January …

We describe a case of liver failure in a child with repeated therapeutic doeses of paracetamol after being given multiple doses to manage pyrexia during a viral illness. The child was treated successfully with only a single loading dose of N-acetylcysteine. This case highlights the importance of parental advice and physician vigilance in preventing hepatotoxicity paracetamol overdose during viral illnesses.

Aims Acute drug overdose, especially with paracetamol, may cause acute liver failure leading to registration for transplantation (ALFT). Population statistics and between-country differences for ALFT related to overdose have been poorly described. The aim of the present study was to evaluate overdose ALFT in the multi-country Study of Acute Liver Transplantation (SALT). Methods All adult overdose-related ALFT, with or without suicidal intent, in France, Greece, Ireland, Italy, the Netherlands, Portugal and the UK between 2005 and 2007 were identified from liver transplant registries and hospital records. These were compared with whole-country and per capita use of paracetamol. Results Six hundred cases of ALFT were identified in 52 of 57 eligible transplant centres, of which 114 involved overdose (72 intentional, 10 non-intentional, 32 uncertain). Overdose represented 20% of all-cause ALFT: Ireland 52%, UK 28%, France 18%, the Netherlands 8%, and Italy 1%. Overdose ALFT were mostly females (61%), mean age 33.6 ± 10.9 years. A total of 111 (97%) of the overdoses involved paracetamol. Event rates ranged from one ALFT for 20.7 tons of paracetamol in Ireland, to one for 1074 tons in Italy and one case in 60 million inhabitants over 3 years in Italy to one case in 286 000 inhabitants per year in Ireland. Per-country event rates for non-overdose ALFT exposed to paracetamol were between 2.5 and 4.0 per million treatment-years sold. Conclusions Paracetamol overdose was found to represent one-sixth of all-cause ALFT. There was a 50-fold difference in Europe in the rates of paracetamol overdose ALFT, and a 200-fold difference per million inhabitants.

A flowchart for the management of patients with paracetamol poisoning is presented to help clinicians in the emergency department.

Severe but regressive toxic liver damage was observed in a 30-week pregnant woman due to acetaminophen poisoning. A cesarean section was performed 1 week later for suspected chorioamniotitis and the patient gave birth to an infant who only experienced complications of preterm birth. The lack of fetal liver damage following acute maternal paracetamol poisoning seems to be the rule, as shown by a review of the literature.

To evaluate reported ingested dose of paracetamol as a risk assessment tool in acute paracetamol overdose. Data was retrospectively obtained from a clinical toxicology database linked to one Australian and two United Kingdom hospitals. Plasma paracetamol concentrations (PPCs) of adult patients presenting with acute single ingestion, non-staggered paracetamol deliberate self-poisoning between 2006 and 2012 were recorded and plotted on a treatment nomogram to determine accuracy of reported dose ingested as an indicator for antidotal treatment. PPC plotted on a treatment nomogram with a line intersecting a 4-h concentration of 100 mg/L [667 μmol/L] was considered an indication for antidotal treatment in the UK; the corresponding Australasian population utilised a line intersecting 150 mg/L [1000 μmol/L]. Of 1246 patients, 65.7 % were female and 88 % were from the UK. Fifty-two percent of patients reporting ingestion of ≥8 g paracetamol had a PPC above the 100 mg/L treatment line; PPV 52 % [95 % confidence interval (CI) 49 %, 55 %], sensitivity 81 % [95 %CI 78 %, 85 %]. Forty-four of patients reporting percent ingestion of ≥10 g had a PPC above the 150 mg/L treatment line; PPV 44 % [95 % CI 41 %, 49 %], sensitivity 85 % [95 % CI 78 %, 89 %], 72 % of patients reporting ingestion of ≥16 g had a PPC above the 100 mg/L treatment line; PPV 72 % [95% CI 67 %, 77 %], sensitivity 50 % [95 % CI 45 %, 54 %]. Overall, there was moderate correlation (R = 0.58) between reported paracetamol dose ingested and extrapolated 4-h PPC. There is a positive correlation between reported ingested dose of paracetamol and subsequent chance of a PPC being above a defined treatment line; however, ingested dose of paracetamol alone is a poor risk assessment tool in accurately determining need for treatment with an antidote.

The aim of this study was to design an information leaflet for patients with paracetamol overdose based on Medicines and Healthcare products Regulatory Agency guidance and to assess its readability. A two-sided one page information leaflet was designed for patients being discharged from hospital after a paracetamol overdose. Patients presenting with an acute paracetamol overdose, irrespective of whether they were treated or not, were recruited to read the leaflet and then answer a brief structured questionnaire based on the leaflet. The readability of the information leaflet was assessed using the Flesch reading ease score. Thirty patients (15 male, 12 female, 3 not recorded; mean age 38 ± 13.0 years) were recruited, wherein 100% of patients reported the language used was understandable, 96.6% knew which symptoms would require urgent medical review after discharge and 100% of patients knew the liver was affected by paracetamol. The Flesch reading ease score was 67.6 (out of a maximum of 100), equivalent to a UK reading age of 10–11years old. Our information leaflet for all patients being discharged after paracetamol overdose was well received by patients, provided them with the required knowledge and had an appropriate reading age based on UK literacy rates. We would recommend that this leaflet could be used as a template on a national level, localized to individual hospitals, to improve patient knowledge of paracetamol toxicity, and facilitate early medical review in the event of deterioration following discharge from the hospital.

Paracetamol overdose may cause hepatic encephalopathy (HE). This condition demands specialized care and, in some instances, liver transplantation evaluation. No model is available for predicting HE. We aimed to set up and validate a model for predicting the occurrence of HE in paracetamol overdose.Prospectively, 161 patients with single-dose paracetamol overdose and no HE (defined as hepatic coma grade II or more) on admission were studied during a 26-month period. Patients admitted during the first 13-month period constituted a learning set to construct a model to predict the occurrence of HE. Patients admitted in the second 13-month period constituted the validation set. Serial biochemical variables (measured twice daily), the time line after the overdose, and demographic data were used for univariate testing, and significant factors were assessed in various multiple logistic regression analyses.Thirty-two patients (20%), 15 in the first period and 17 in the second, developed HE grade II. The best model (the highest chi-square) for HE included: log10 (hours from overdose to antidote treatment), log10 (plasma coagulation factors on admission), and platelet count hours from overdose (chi-square = 41.2, P0.00001). In the validation set 88% (confidence interval (CI), 64%-99%) of the patients who developed HE were correctly predicted by the constructed model, whereas 90% (CI, 79%-96%) of the patients in the non-HE group were correctly predicted.The constructed model for predicting HE in paracetamol overdose proved sensitive and accurate in the validation set and should be valuable for transferring high-risk patients to a liver intensive care unit/transplantation facility.

The recent article by Wong et al., stated the multiplication product of serum aminotransferase (ALT) activity and paracetamol concentration (APAP) as a predictor of subsequent hepatotoxicity.1 When...

One of the most common causes of acute liver failure in the Western world is paracetamol (acetaminophen) overdose. Specific and sensitive detection of liver injury is important for the prompt and safe treatment of patients with the antidote N-acetylcysteine (NAC) and for the determination of NAC efficacy. Despite many years of intense research, the precise mechanisms of paracetamol-induced liver injury in humans are still not defined, and few studies have examined the optimal dosing regimen for clinical NAC use. It has been widely acknowledged that circulating biomarkers such as microRNA-122, keratin-18 and high mobility group box-1 hold potential to inform on the mechanistic-basis of human drug-induced liver injury. Here, we provide a perspective on the application of these mechanistic biomarkers to the deeper understanding of paracetamol hepatotoxicity in clinical and preclinical studies. Also, we discuss current barriers to using these experimental biomarkers to stratify patients presenting to hospital with this common medical emergency.

In September 2012, the Medicines and Healthcare products Regulatory Agency (MHRA) published new guidance regarding the use of acetylcysteine in the treatment of paracetamol toxicity in both adults and children1 The meeting of an expert paracetamol group was tasked ‘to review the available preclinical and clinical evidence on the use of acetylcysteine for the treatment of paracetamol overdose including a review of worldwide experience’. The 2010–2011 edition of the British National Formulary for Children (BNFc) 2 and TOXBASE3 suggested that a single acute paracetamol overdose of 150 mg/kg (75 mg/kg in high risk patients) may result in severe hepatocellular necrosis and renal tubular necrosis. After patients had been stratified into either ‘high risk’ or ‘low risk’ of liver damage (based upon concurrent use of enzyme-inducing drugs, malnourishment or febrile illness), plasma paracetamol levels were to be taken and compared with the relevant treatment line on a standardised nomogram. Assuming presentation was within 24 h of ingestion and there was no evidence of staggered overdose, levels above the treatment line would suggest treatment with acetylcysteine was indicated. Once the decision-to-treat had been made, a total of …

OBJECTIVE Adverse drug reactions (ADRs) to N-acetylcysteine (NAC) treatment for paracetamol overdose are typically anaphylactoid in origin and occur in 2-48% of treated patients. We explored the incidence and management of NAC ADR in our unit. PATIENTS AND METHODS Case notes of patients who presented with paracetamol overdose and had ADR to NAC between February 2005 and June 2011 were reviewed. A total of 1648 patients presented with suspected paracetamol overdose and 660 received NAC treatment. Within this group, 82 patients had documented NAC-related ADR. RESULTS ADR developed in 12.4% (82/660) of patients receiving intravenous NAC and 59 had full documentation available and were included in this study (34 women, 25 men). ADR occurred in the 15-min (150 mg/kg) bag in 36 cases (61%), 22 in the 4-h (50 mg/kg) bag (37%) and one in the 16-h (100 mg/kg) bag (2%). Symptoms were classified as minimal (n=16, 27%), moderate (n=26, 44%) and severe (n=17, 29%). Asthma and female sex, which are reported risk factors for ADR, did not lead to the development of more severe ADR (P=0.771 and 0.330, respectively). Treatments administered included stopping the NAC infusion (n=32, 54%), administration of antiemetics (n=36, 61%), H1 antihistamines (n=26, 44%), steroids (n=16, 27%), inhaled B2 agonists (n=6, 10%) and adrenaline (n=3, 5%). CONCLUSION The incidence of ADR to NAC was comparable with published studies, although there was no association of severity with asthma or female sex. The management of ADRs is variable, with frequent, inappropriate use of steroids. Education about the pathophysiology of these ADRs may improve management.

In September 2012, the Medicines and Healthcare products Regulatory Agency (MHRA) substantially amended the Marketing Authorisation for acetylcysteine following an extensive review. The present study examined the impact of this license change on patterns of acetylcysteine use in patients presenting to hospital after paracetamol (acetaminophen) overdose. Between September 2011 and April 2013, 785 consecutive patients presented to York Hospital due to paracetamol overdose, and a before-after analysis was used to compare outcomes. There were 483 patients before and 302 patients after the license amendment, and age, gender, acute or staggered overdose pattern, and dose were similar in both groups. In the patients with paracetamol concentrations between the “100-line” and “200-line,” a significantly higher proportion received acetylcysteine treatment (51% before versus 98% after, P = 0.0029), as expected. A modest increase was also observed in relation to late or staggered overdose or cases where the time of ingestion was uncertain (53% versus 74%, P = 0.0430). The median duration of hospital stay increased across the entire study population, from 15 to 24 hours (P = 0.0159) due to the increased proportion of patients requiring acetylcysteine treatment. The findings indicate that the MHRA amendment is a financially costly intervention, and further studies are needed to examine clinical outcomes so that its cost effectiveness might be addressed.

N-acetylcysteine (NAC) is acknowledged as an effective antidote for paracetamol overdose. However, adverse effects to NAC are common and may be a point of concern for the patient and the treating physician.The aim of the present study was to further analyse possible risk factors of anaphylactoid adverse effects to intravenous NAC in order to identify individual patients or groups of patients at particular risk.This study is an observational case series of adverse effects to NAC administered according to the standard guidelines in patients who presented with paracetamol overdose between March 1999 and September 2011.A total of 1218 admissions for paracetamol overdose receiving intravenous NAC were recorded in 950 patients. Anaphylactoid adverse effects occurred in 18.6%. The proportion of cases with adverse effects gradually declined from 25.9% in cases with undetectable p-paracetamol to 6.3% in cases with p-paracetamol above 1.5 mmol/L (226 μg/mL) (Spearman Rank R-test: p0.00001). The proportion of cases with adverse effects was significantly higher in cases of non-Danish origin than that of Danish origin (28.5% vs. 15.1%; Chi-square: p0.00001). In patients with repeated exposure to NAC, the rate of adverse effects on re-exposure was significantly higher in patients with a previous reaction to NAC compared to those without a previous reaction (Rate Ratio 6.2; 95% CI 2.9-17.1).The development of anaphylactoid adverse effects to intravenous NAC was strongly associated with a low p-paracetamol, non-Danish origin and a history of previous reaction to NAC. These adverse effects are common, but usually mild and easily manageable. The incidence of adverse effects may be reduced by pre-treating selected patients with antihistamines, in particular those with a previous reaction to NAC.

We note that the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (Study of Acute Liver Transplantation) in the UK1—63 cases in 2005-07 (5.25 cases per quarter)—was the same as that reported by Hawton and colleagues.2 However, in the UK and …

Paracetamol overdose now represents one third of all self poisoning cases. In contrast to other drugs, the use of paracetamol as a self-poisoning agent is increasing. As very large doses of the drug cause severe liver injury, which can result in fulminant hepatic failure when left untreated, it is essential that nurses have a complete understanding of the mechanisms of normal paracetamol metabolism, effects of overdosage and treatment strategies to guide the nursing management of clients. This review therefore critically examines the pathophysiology and nursing management of clients with acute paracetamol overdosage.

En lactantes menores de 6 meses la intoxicación por paracetamol suele ser secundaria a un error de dosificación por parte de los cuidadores. Recientemente se han comercializado presentaciones líquidas de paracetamol en envases mayores (60 ml). Adjuntan una jeringa administradora también mayor (5 ml frente a 1,2–2 ml). Presentamos 6 casos de lactantes de 2–4 meses que recibieron por equivocación dosis superiores a las terapéuticas, en todos ellos se trataba de un frasco de 60 ml. Estos pacientes son especialmente susceptibles por su inmadurez hepática a la intoxicación, requiriendo un tratamiento más agresivo. Para prevenir estas intoxicaciones, es fundamental una correcta información a los cuidadores sobre la posología de los fármacos : In infants under 6 months of age, paracetamol overdose is usually due to dose confusion by caretakers. Recently, liquid formulations of this drug have been commercialized in larger,60-ml bottles. The syringe to measure the syrup in these new formulations is also bigger (5 cc versus 1.2–2 cc). We present six cases of 2–4-month-old infants mistakenly given an overdose of paracetamol, each from this new 60-ml formulation. These patients are especially susceptible to poisoning because of liver immaturity and require more aggressive management. To prevent this kind of poisoning, correct and clear information must be given to caregivers about drug dosage

Restrictions on easy access to paracetamol have reduced death from paracetamol overdose in the UK. However, figures from Newcastle show that hanging and jumping deaths have become more common.[1][1] Since paracetamol overdoses are usually not instantly fatal, second thoughts are possible. This is