Whole-bowel irrigation should not be used routinely in poisoned patients.

Whole-bowel irrigation is a method of gastric decontamination in the poisoned patient involving administration of large volumes of osmotically balanced polyethylene glycol-electrolyte solution to empty the gastrointestinal tract of ingested toxins before absorption, limiting systemic toxicity. While this approach may seem intuitive, and observational studies confirm it can lead to expulsion of tablets or packets in the rectal effluent, there is a lack of evidence correlating this with improved patient outcomes. Administration of whole-bowel irrigation is also challenging to the inexperienced physician and associated with adverse effects, which may be serious. Recommendations for whole-bowel irrigation are therefore limited to patients who have ingested modified-release preparations, those who have ingested pharmaceuticals not adsorbed by activated charcoal and for the removal of packages in "body packers". Until more robust evidence is available from high-quality prospective studies demonstrating efficacy, the use of whole-bowel irrigation should not be used routinely in poisoned patients.

Carbon monoxide exposures reported to the UK National Poisons Information Service: a 4-year study.

BACKGROUND: Unintentional carbon monoxide (CO) poisoning poses a public health challenge. The UK National Poisons Information Service (NPIS) provides advice to healthcare professionals via the online database, TOXBASE®, and a 24-hour telephone line. Our aim was to analyse all CO-related enquiries to the NPIS. METHODS: We analysed enquiries regarding unintentional CO exposure (1st July 2015-30th June 2019). Information on patient demographics, CO source and location, clinical features and poisoning severity was collected from telephone enquiries and TOXBASE accesses. RESULTS: 2970 unintentional non-fire-related CO exposures were reported. Exposures occurred commonly in the home (60%) with faulty boilers frequently implicated (27.4%). Although five fatalities were reported, 68.7% of patients experienced no or minor symptoms only (headache most frequently reported). Despite being the gold standard measurement, blood carboxyhaemoglobin concentration was only recorded in 25.6% patients, with no statistically significant correlation with severity. CONCLUSIONS: Unintentional CO exposures in the UK commonly occur in domestic settings and although are generally of low severity, fatalities continue to occur. Carboxyhaemoglobin measurement is important to confirm exposure but further work is required to assess its validity as a prognostic indicator in CO exposure. Public health policy should continue to focus on raising awareness of the dangers of CO.

Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial.

BACKGROUND: Paracetamol poisoning is common worldwide. It is treated with intravenous acetylcysteine, but the standard regimen is complex and associated with frequent adverse effects related to concentration, which can cause treatment interruption. We aimed to ascertain whether adverse effects could be reduced with either a shorter modified acetylcysteine schedule, antiemetic pretreatment, or both. METHODS: We undertook a double-blind, randomised factorial study at three UK hospitals, between Sept 6, 2010, and Dec 31, 2012. We randomly allocated patients with acute paracetamol overdose to either the standard intravenous acetylcysteine regimen (duration 20·25 h) or a shorter (12 h) modified protocol, with or without intravenous ondansetron pretreatment (4 mg). Masking was achieved by infusion of 5% dextrose (during acetylcysteine delivery) or saline (for antiemetic pretreatment). Randomisation was done via the internet and included a minimisation procedure by prognostic factors. The primary outcome was absence of vomiting, retching, or need for rescue antiemetic treatment at 2 h. Prespecified secondary outcomes included a greater than 50% increase in alanine aminotransferase activity over the admission value. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov (identifier NCT01050270). FINDINGS: Of 222 patients who underwent randomisation, 217 were assessable 2 h after the start of acetylcysteine treatment. Vomiting, retching, or need for rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to the shorter modified protocol compared with 71 of 109 allocated to the standard acetylcysteine regimen (adjusted odds ratio 0·26, 97·5% CI 0·13-0·52; p<0·0001), and in 45 of 109 patients who received ondansetron compared with 65 of 108 allocated placebo (0·41, 0·20-0·80; p=0·003). Severe anaphylactoid reactions were recorded in five patients assigned to the shorter modified acetylcysteine regimen versus 31 who were allocated to the standard protocol (adjusted common odds ratio 0·23, 97·5% CI 0·12-0·43; p<0·0001). The proportion of patients with a 50% increase in alanine aminotransferase activity did not differ between the standard (9/110) and shorter modified (13/112) regimens (adjusted odds ratio 0·60, 97·5% CI 0·20-1·83); however, the proportion was higher with ondansetron (16/111) than with placebo (6/111; 3·30, 1·01-10·72; p=0·024). INTERPRETATION: In patients with paracetamol poisoning, a 12 h modified acetylcysteine regimen resulted in less vomiting, fewer anaphylactoid reactions, and reduced need for treatment interruption. This study was not powered to detect non-inferiority of the shorter protocol versus the standard approach; therefore, further research is needed to confirm the efficacy of the 12 h modified acetylcysteine regimen. FUNDING: Chief Scientist Office of the Scottish Government.

Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment.

AIMS: In September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single '100 mg l(-1) ' nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. METHODS: Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. RESULTS: There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI -4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million-10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million-21.5 million). CONCLUSIONS: The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.

Measurement of renal function in patients with chronic kidney disease.

Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

Histamine-induced vasodilatation in the human forearm vasculature.

AIM: To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature. METHODS: Three studies were conducted to assess changes in forearm blood flow (FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose-response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H1 - and H2 -receptor antagonists. Flare and itch were assessed in all studies. RESULTS: Histamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min(-1) ) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6 ml min(-1) 100 ml(-1) ; P < 0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H2 -receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30 nmol min(-1) histamine: -11.9 ml min(-1) 100 ml(-1) (-4.0, -19.8), P < 0.0001) and flare (mean (95% CI) difference from placebo: -403.7 cm(2) (-231.4, 576.0), P < 0.0001). No reduction in FBF or flare was observed in response to the H1 -receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor. CONCLUSION: Histamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H2 -receptors are important in this process. Our results support further exploration of combined H1 - and H2 -receptor antagonist therapy in acute allergic syndromes.

Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019: a ten-year retrospective analysis.

INTRODUCTION: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. METHODS: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. RESULTS: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. DISCUSSION: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. CONCLUSIONS: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

BACKGROUND: Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. METHODS/DESIGN: We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. DISCUSSION: Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. TRIAL REGISTRATION: Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

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.

Potential cyanide poisoning reported to the UK national poisons information service: 2008-2019.

INTRODUCTION: Cyanide is a prevalent, lethal chemical. Possible sources of exposure include products of combustion, plant material, industry, chemical warfare and terrorism. METHODS: Retrospective review of UK Poisons Information Database of telephone enquiries to the National Poisons Information Service between 1st January 2008 and 31st December 2019 where cyanide poisoning was considered a possibility. Data extracted included demographics, exposure source, clinical features, Poisoning Severity Score, lactate concentration and antidotes given. RESULTS: A total of 1,252 cases of suspected cyanide poisoning were identified, 239 (19%) involved children under 10 years. The commonest sources of exposure were ingestion of plant material (437 cases; 35%) and smoke inhalation (399; 32%). Smoke inhalation caused the majority of severe and fatal cases (139; 71%). Clinical features associated with fatal outcomes were cardiac arrest (OR 36.4; 95% CI 14.4-92.2), hypotension (15.8; 7.0-35.9), coma (10.8; 5.6-21.0) and lactic acidosis (7.8; 4.1-14.8). 110 patients (9%) were given an antidote and 40 patients (3%) died.Lactate concentrations correlate with Poisoning Severity Score category (r = 0.6, p < 0.0001). Serum lactate <2.0 mmol/L was associated with Poisoning Severity Score None or Minor (sensitivity 76%; specificity 86%) and >11.0 mmol/L was associated with fatal outcome (sensitivity 74%; specificity 80%). 61 cases (5%) had severe carboxyhaemoglobin toxicity (COHb >30%). This was associated with a fatal outcome (OR 7.0; 95% CI 1.5-33.7) and there was positive correlation between carboxyhaemoglobin and Poisoning Severity Score, r = 0.57, p < 0.0001. CONCLUSIONS: Most cases of ingestion of plant material involved children under five years and resulted in no or mild symptoms. In adults smoke inhalation was associated with the most severe poisoning. The lactate cut-off values associated with each severity score calculated in this study are lower than the values used by NPIS on TOXBASE. Analytical conformation of cyanide exposure was unavailable in the majority of case, limiting the strength of these conclusions.

Bites by exotic snakes reported to the UK National Poisons Information Service 2009-2020.

Introduction: Snakebite is recognised as a neglected tropical disease and a cause of substantial morbidity and mortality. Whilst the most medically important snakes are typically native of Asia, Africa, Latin America and Oceania, the possibility of encountering these snakes is no longer limited by geography due to an increasing number of exotic (non-native) snakes being held in captivity.Methods: A retrospective review of snakebite enquiries to the UK National Poisons Information Service (NPIS) between 2009 and 2020. Enquiries about the European adder (Vipera berus) or where the identity of the snake was unknown were excluded.Results: There were 321 exotic snakebites in 300 patients involving 68 different species during this period. Ten patients were bitten on more than one occasion. The majority of patients (64.5%) were male. Most bites were inflicted by snakes of the family Colubridae (184/321, 57.3%); seventeen bites resulted in moderate symptoms (predominantly swelling of the bitten limb). There were 30 (9.3%) bites by Viperidae and 14 (4.3%) bites by Elapidae. All severe cases (n = 15) resulted from bites by either Viperidae (n = 10) or Elapidae (n = 5). Antivenom was given in 17 cases. One fatality was recorded.Conclusions: Despite their low incidence, exotic snakebites present a substantial challenge for UK healthcare professionals. Although rare, these bites typically occur in individuals (usually male) who keep snakes as part of their occupation or hobby and are therefore at risk of multiple bites. Bites can result in venom hypersensitisation and the risk of venom-induced anaphylaxis. Rapid access to expert clinical advice is available in the UK on a 24-hour basis through the National Poisons Information Service and is strongly recommended in all cases of exotic snakebite.

Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy: A Failure of Academic Clinical Science.

Contrast-induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)-acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double-blind, placebo-controlled, three-period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso-osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three-arm randomized, double-blind, placebo-controlled parallel-group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno-protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working.

Impact of a focussed teaching programme on practical prescribing skills among final year medical students.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Medication errors, and particularly prescribing errors, are common in UK hospitals. Junior doctors make the majority of prescribing errors. Deficiencies in prescribing education and training have been closely linked to the high frequency of medication errors. WHAT THIS STUDY ADDS: Focussed prescribing teaching can lead to an improvement in prescribing ability. Prescribing confidence can be significantly improved through education. Education is insufficient alone in eradicating prescribing errors. AIM: To assess the impact of prescribing teaching on final year medical students. METHODS: Students randomly allocated to two hospitals completed a prescribing assessment. Prescribing teaching was delivered to the intervention group while no additional teaching was provided for the control group. All students then completed a second prescribing assessment. RESULTS: Teaching improved the assessment score: mean assessment 2 vs. 1, 70% vs. 62%, P= 0.007; allergy documentation: 98% vs. 74%, P= 0.0001; and confidence. However, 30% of prescriptions continued to include prescribing errors. CONCLUSION: Medical students make significant errors in prescribing. Teaching improves ability and confidence but is insufficient alone in eradicating errors.

Paradoxical refractory hypotension following adrenaline administration in a patient taking clozapine.

Clozapine is a potent antipsychotic commonly used for refractory schizophrenia. Adverse effects are well recognised including constipation, intestinal obstruction, agranulocytosis and cardiomyopathy. We present a case of paradoxical refractory hypotension following epinephrine administration in a patient taking clozapine. A psychiatric inpatient who had been taking clozapine for many years developed paralytic ileus and obstruction requiring surgical intervention. Following initiation of epinephrine administration intraoperatively he developed refractory hypotension which improved only when epinephrine was weaned off. This effect is likely due to uninterrupted ß2-agonist activity in the presence of clozapine-induced α-blockade. Clinicians need to have greater awareness of this serious interaction and avoid the use of epinephrine in patients taking clozapine.

A review of 4652 exposures to liquid laundry detergent capsules reported to the United Kingdom National Poisons Information Service 2008-2018.

Introduction: Liquid laundry detergent capsules contain concentrated liquid laundry detergent in a water-soluble polyvinyl alcohol membrane.Objective: To review 4652 exposures reported to the United Kingdom National Poisons Information Service (NPIS) and to assess the impact of regulatory changes on potential toxicity.Methods: Telephone enquiries to the NPIS and returned questionnaires for these products were analyzed for the period January 2008 to December 2018.Results: Data on 4652 exposures were reported by telephone or questionnaire, of which 95.4% involved children aged ≤5 years. Overall, 1738 of 4594 patients remained asymptomatic (Poisoning Severity Score [PSS] 0), 2729 developed minor (PSS 1) features, 107 suffered moderate features (PSS 2), 19 were graded as severe (PSS 3) and one died. Ingestion was involved in most exposures (n = 4175): vomiting occurred in 46.5%, coughing occurred in 4.3% and central nervous system depression in 3.2%. Nine (0.2%) children were intubated and ventilated. The eye was exposed in 646 cases: 371 (59.8%) suffered conjunctivitis or eye irritation and 21 (3.4%) had keratitis/corneal damage, which persisted in one patient for 9 d. The skin was involved in 364 cases; in 127 (35.5%) minor dermal features developed including erythema, irritation and rash. The most commonly reported features in the 127 cases with PSS ≥2 were vomiting (n = 75), stridor (n = 34), CNS depression (n = 22), keratitis/corneal damage (n = 21), coughing (n = 18), conjunctivitis (n = 13), hypersalivation (n = 12), foaming from the mouth (n = 11) and hypoxemia (n = 11). However, respiratory features (stridor, hypoxemia, bronchospasm, respiratory distress, dyspnea, pulmonary aspiration and tachypnea) were the reason for grading 56 of 127 cases as PSS ≥2.Conclusions: This large data set of 4652 exposures is reassuring in that 97.2% of exposures resulted in no or only minor features, only 107 patients suffered moderate features (PSS 2) and 19 severe (PSS 3) features; one patient died.

Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose.

BACKGROUND: Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) Study demonstrated that a 12 h NAC regimen was associated with fewer adverse drug reactions compared with the standard 21 h regimen. Here, we describe the clinical effectiveness of the SNAP NAC regimen. METHODS: The SNAP regimen, consisting of intravenous NAC 100 mg/kg over 2 h then 200 mg/kg over 10 h, was introduced to treat all paracetamol overdose patients at the Royal Infirmary of Edinburgh, the Royal Victoria Infirmary, Newcastle and St Thomas' Hospital, London. Patient data were prospectively and systematically collected before and after the change in treatment (total patients N = 3340, 21 h N = 1488, SNAP N = 1852). Health record linkage was used to determine patient outcome after hospital discharge. FINDINGS: There was no difference in liver injury or liver synthetic dysfunction between regimens. Hepatotoxicity (peak ALT > 1000 U/L) occurred in 64 (4.3%) and 67 (3.6%) patients, respectively, in the 21 h and SNAP groups (absolute difference - 0.7%, 95% CI - 2.1 to 0.6). Multivariable logistic regression did not identify treatment regimen as an outcome-associated factor. No patients were readmitted to hospital with, or died from, liver failure within 30 days of discharge. Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients with the 21 h regimen and 37 (2.0%) patients with the SNAP regimen (absolute difference 9.0% (95% CI 7.3 to 10.7)). INTERPRETATION: In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions.

Co-proxamol withdrawal has reduced suicide from drugs in Scotland.

AIM: To determine what effect the withdrawal of co-proxamol from the UK market has had on mortality from poisoning in Scotland. METHODS: This was a retrospective, observational study of mortality relating to poisoning by single agents in Scotland for the period 2000-2006. Mortality data were obtained from the General Register Office Scotland, and primary care prescribing data from the Information and Statistics Division of the Scottish Executive Health Department. RESULTS: A significant reduction in the proportion of poisoning deaths due to co-proxamol was observed following legislation [mean 2000-2004, 37 deaths (21.8% of total poisoning deaths); 2006, 10 (7.8%); P < 0.0001]. The most significant reduction was seen in male out-of-hospital deaths [mean 2000-2004, 17 (21.8%); 2006, two (2.9%); P < 0.0001]. This was associated with a decline in prescriptions by 60% within 6 months of legislation. The total number of poisoning deaths also fell, slightly earlier than the full impact on co-proxamol deaths (mean 2000-2004, 171.2; mean 2005-2006, 129.5; P = 0.005). CONCLUSIONS: Legislation has resulted in a major reduction in the number of deaths associated with co-proxamol poisoning in Scotland, with no compensatory rise in mortality from poisonings from other common analgesics. We estimate from this study that a minimum of 300 lives across the UK will have been saved by the withdrawal of co-proxamol.

Exposures to automatic dishwashing rinse aids reported to the United Kingdom National Poisons Information Service 2008-2016.

OBJECTIVE: To determine the toxicity of rinse aids which are used as drying aids to remove water from crockery. METHODS: Enquiries to the UK National Poisons Information Service (NPIS) were analysed retrospectively for the period January 2008 to December 2016. RESULTS: There were 855 enquiries relating to 828 patients; children aged 5 years or less accounted for 91.1%. Most exposures occurred from ingestion alone (n = 778, 94.0%), but 26 involved ingestion and other routes: 21 with skin contact, 3 with eye contact, and two with both skin and eye contact. There were a further 24 cases of eye contact alone (n = 20, 2.4%) or skin contact alone (n = 3, 0.4%) and a single case of inhalation alone. The World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists (WHO/IPCS/EC/EAPCCT) Poisoning severity score [PSS] was known in 824 of the 828 exposures: 425 of 824 (51.6%) patients did not develop clinical features, 381 (46.2%) had a PSS of 1 (minor toxicity), 15 (1.8%) developed moderate (PSS 2) and 3 (0.4%) severe (PSS 3) toxicity. Vomiting was the most common feature, occurring in over a third of all ingestions (n = 286, 35.8%), followed by coughing (n = 73, 9.1%). A higher proportion of adults than children developed clinical features (72.7% of 33 vs 46.0% of 767, p = .0026), although vomiting occurred significantly more frequently amongst children (p = .0315). Of the 25 eye contact cases, eye pain (n = 8) and/or eye irritation (n = 8) were reported, with or without abnormal vision (n = 7); there were two cases of corneal abrasion. Dermal contact rarely produced features; only 4 of 26 patients reported symptoms including skin rash or burning or numbness at the contact site. CONCLUSIONS: Severe clinical features were uncommon following rinse aid exposure; vomiting was the most frequently reported symptom following ingestion.

Reductions in emergency department visits after primary healthcare use of the UK National Poisons Information Service.

BACKGROUND: Suspected poisoning is a common cause of hospital admission internationally. In the United Kingdom, the National Poisons Information Service (NPIS), a network of four poisons units, provides specialist advice to health professionals on the management of poisoning by telephone and via its online poisoning information and management database, TOXBASE®. OBJECTIVE: To demonstrate the impact of NPIS telephone advice and TOXBASE® guidance on poisoning-related referrals to emergency departments (ED) from primary healthcare settings. METHODS: A telephone survey of primary healthcare providers calling the NPIS and an online survey of TOXBASE® primary care users were conducted to evaluate the effect of these services on poisoning-related ED referrals. Enquirers were asked to indicate whether referral was needed before and after using these information sources. RESULTS: The number of cases considered by enquirers appropriate for ED referral was reduced from 1178 (58.1%) before to 819 (40.4%) after the provision of telephone advice for 2028 cases (absolute reduction 17.7%, 95% CI 14.6, 20.7%) and from 410 (48.2%) before to 341 (40.1%) after consideration of TOXBASE® guidance for 851 cases (absolute reduction 8.1%, 95% CI 3.3, 12.9%). By extrapolating these figures over a full year, it is estimated that these services prevent approximately 41,000 ED referrals annually. CONCLUSIONS: The use of NPIS services significantly reduced ED referrals from primary healthcare services with resulting avoided healthcare costs exceeding the current annual NPIS budget. Further studies are needed to evaluate other potential benefits of accessing NPIS services.

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.