Large paracetamol overdose-Higher dose acetylcysteine is required.

Paracetamol poisoning continues to be a worldwide problem and, despite the availability of an effective antidote, acetylcysteine (NAC), the optimal way to use this antidote, particularly following very large doses of paracetamol, has not been established. Recent case series have shown an increased toxicity from high doses of paracetamol, even in those receiving prompt NAC therapy, particularly in patients above the 300 mg/L nomogram treatment line. Clinical trial evidence supporting shorter NAC dosing now allows the possibility for intensifying treatment without the risk of very high rates of ADRs. New biomarkers also show the possibility of early identification of patients at risk of liver injury who might also benefit from increased intensity treatment. This article discusses these data and proposes a logical therapy for increasing NAC dosing which now requires clinical trial testing.

Toxicity of phosphate enemas - an updated review.

INTRODUCTION: Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports. OBJECTIVES: To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups. METHODS: A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted. RESULTS: The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported. CONCLUSION: Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.

Iron overdose epidemiology, clinical features and iron concentration-effect relationships: the UK experience 2008-2017.

Background: Iron poisoning is potentially serious, but mortality has fallen worldwide since implementation of pack size and packaging restrictions, and changes in iron use during pregnancy. The management of individual cases of overdose remains problematic due to uncertainty about indications for antidote. We examine the epidemiology of iron overdose in hospital cases referred to the UK National Poisons Information Service (NPIS) and evaluate the toxicokinetics of iron in patients ingesting only iron preparations. Methods: Anonymized hospital referral patient data from the NPIS database were collated for the period 1 January 2008 to 31 July 2017. Information was extracted, where recorded, on type of ingestion [iron alone (single), or combined with other agents (mixed)], reported dose, iron salt, timed iron concentrations and symptoms. In single-agent ingestions, the relationships between reported elemental iron dose, early concentrations (4-6 h), and symptoms were evaluated in teenagers and adults (≥13 years) and children (≤12 years) using standard statistical techniques (correlation and unpaired nonparametric comparisons). In those patients with sufficient sample points (three or more), a simple kinetic analysis was conducted. Results: Of 2708 patients with iron overdoses referred by UK hospitals for advice during the 9.7 years study period, 1839 were single-agent ingestions. There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%) were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years (91% females), the latter a substantial excess over the proportion in the totality of hospital referrals to the NPIS in the same period (13-20 years: 23,776/144,268 16.5%; 67.5% female) (p < .0001 overall and for female %). In 475 teenagers and adults and 86 children, with at least one-timed iron concentration available, there was no correlation between stated dose and iron concentration measured 4-6 h post-ingestion. Observed peak iron concentrations were not related to reported symptoms in adults. Initial iron concentrations were significantly higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO) compared to those that did not [no DFO: mean 63.8 µmol/L (95% CI 62.1-65.6), median 64; DFO: mean 78.5 µmol/L (95% CI 69.2-87.7), median 78.1; Mann-Whitney p < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. Conclusion: Single-agent iron exposures reported from UK hospitals were most common in children <5 years and young people aged 13-20 years. Poisoning with organ failure was not identified and there were no fatalities. No correlations were observed between reported iron doses and early concentrations, or between iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.

An integrated care pathway improves the management of paracetamol poisoning.

BACKGROUND: Paracetamol poisoning remains a major cause of morbidity and mortality. Clinical care of paracetamol poisoning depends on a range of patient variables and typically involves both medical and nursing care. An integrated care pathway (ICP) is a multidisciplinary management plan that incorporates guidelines and best practice to enhance care and documentation for a specific patient group. Paracetamol overdose is thus amenable to an ICP. AIM: To evaluate the introduction of an ICP on process of care of the paracetamol poisoned patient. METHODS: A retrospective case note review of consecutive patients admitted to the Royal Infirmary of Edinburgh following a paracetamol overdose was conducted. Data were collected for a 3-month period before and after introduction of the ICP to the emergency department and toxicology inpatient unit. RESULTS: The ICP was used in 77% of cases in the time period studied and was associated with improvements in initial documentation of patient assessment (pre-ICP vs post-ICP: 87/161 (54%) vs 101/113 (89%), p<0.0001) and appropriateness of blood sampling (146/161 (91%) vs 111/113 (98%), p=0.01), but no change in timely blood sampling (pre 124/161 (77%) vs post 93/113 (82%)). All aspects of intravenous acetylcysteine administration also significantly improved: administration of acetylcysteine if indicated (pre-ICP vs post-ICP: 57/71 (80%) vs 71/71 (100%), p<0.0001); acetylcysteine commenced in a timely fashion (33/71 (46%) vs 55/71 (77%), p=0.0002); and acetylcysteine correctly prescribed (44/58 (76%) vs 71/71 (100%), p<0.0001). CONCLUSIONS: Implementation of an ICP for paracetamol poisoning significantly improved patient management and helped to standardise inter-professional decision making in this challenging patient group. This is likely to improve patient outcome.

Differences in treatment advice for common poisons by poisons centres--an international comparison.

OBJECTIVE: To investigate how poisons centres advise on management of common drug poisonings and compare advice on gut decontamination with the EAPCCT/AACT Position Statements. METHODS: An interactive questionnaire was sent to 14 poisons centres asking about working practices, "top 20" enquiries in 2002, and management of 4 specific drug poisonings. RESULTS: Replies were received from centres in 11 countries. Annual telephone enquiry numbers varied from 620 (Sri Lanka) to over 50,000 (Germany for 2000). Recommendations for gut decontamination for acetaminophen poisoning were: activated charcoal (AC) alone (5 centres); gastric lavage (GL) alone (1); AC and/or GL (3); AC, GL and/or ipecac (2). Only 40% (4/10) recommended AC and 50% (3/6) GL within 1 hour. Intervention doses for gut decontamination ranged from 100-200 mg/kg (nine centres) and for "high-risk" groups 75-100 mg/kg (3). Plasma concentration for N-acetylcysteine (NAC) treatment ranged from 150 mg/L (four centres) to 200 mg/L (6) at 4 hours. Results were similarly varied for three other common drug poisons (benzodiazepines, amitriptyline, and paroxetine). CONCLUSIONS: Most poisons centres have protocols that differ in terms of gut decontamination, timing, and intervention doses. Many centres recommend charcoal or gastric lavage after the 1-hour limit proposed in the Position Statements. There is scope for rationalization of approaches to the management of common poisons.