Publications by authors named "Euan Sandilands"

33 Publications

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

Clin Toxicol (Phila) 2022 Jul 19:1-7. Epub 2022 Jul 19.

National Poisons Information Service Birmingham, Birmingham, United Kingdom of Great Britain and Northern Ireland.

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. A retrospective review of snakebite enquiries to the UK National Poisons Information Service (NPIS) between 2009 and 2020. Enquiries about the European adder ( or where the identity of the snake was unknown were excluded. 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 ( = 15) resulted from bites by either Viperidae ( = 10) or Elapidae ( = 5). Antivenom was given in 17 cases. One fatality was recorded. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2077748DOI Listing
July 2022

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

Clin Toxicol (Phila) 2022 May 30:1-8. Epub 2022 May 30.

National Poisons Information Service, Cardiff Unit, University Hospital Llandough, Penarth, UK.

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 1 January 2008 and 31 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 ( = 0.6,  < 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,  = 0.57,  < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2022.2080074DOI Listing
May 2022

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

Clin Pharmacol Ther 2022 06 23;111(6):1222-1238. Epub 2022 Feb 23.

Pharmacology, Toxicology, and Therapeutics, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpt.2541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306485PMC
June 2022

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

BMJ Case Rep 2021 Nov 1;14(11). Epub 2021 Nov 1.

Department of Acute Medicine, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK

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 β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2021-243363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562354PMC
November 2021

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

J Public Health (Oxf) 2021 May 17. Epub 2021 May 17.

National Poisons Information Service (Edinburgh Unit), Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pubmed/fdab132DOI Listing
May 2021

Radiology for medical students: Do we teach enough? A national study.

Br J Radiol 2021 Mar 9;94(1119):20201308. Epub 2021 Feb 9.

Edinburgh Medical School, Edinburgh, United Kingdom.

Objective: A recent study has shown that the averaged time tabled teaching for a medical student across 5 years in the UK was 4629 hours. Radiology has been demonstrated to be an excellent teaching source, yet the number of hours allocated to this has never been calculated.The aims of this study were to evaluate and quantify the hours allocated to radiology teaching in Scottish Medical Schools and to evaluate if they can fulfil requirements expected from other Clinical disciplines and the upcoming General Medical Council Medical Licensing Assessment (GMC MLA).

Methods: Data pertaining to timetabled teaching for Radiology in Scottish Universities were obtained from the authors of the Analysis of Teaching of Medical Schools (AToMS) survey. In addition, University Lead Clinician Teachers were surveyed on the radiological investigations and skills medical students should have at graduation.

Results: Medical students in Scottish Universities were allocated 59 h in Radiology (0.3%) out of a total 19,325 h of timetabled teaching. Hospital-based teaching was variable and ranged from 0 to 31 h. Almost half (15 of 31) of Clinician Teachers felt that there was insufficient radiology teaching in their specialty. Thirteen of 30 conditions included in the GMC MLA were listed by Clinician Teachers, while 23 others not listed by the GMC were considered important and cited by them.

Conclusion: This study demonstrates that medical students do not receive enough radiology teaching. This needs to be addressed by Universities in collaboration with the NHS in an effort to bring up this up to line with other developed countries and prepare students for the GMC MLA.

Advances In Knowledge: (1) There is insufficient time allocated in Medical Students' curriculum to Radiology.(2) Radiology teaching in medical schools fall short of University Lead Clinician Teachers' and GMC expectations of medical students at graduation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20201308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011254PMC
March 2021

Use of the online poisons information database TOXBASE and admissions rates for poisoned patients from emergency departments in England and Wales during 2008 to 2015.

J Am Coll Emerg Physicians Open 2020 Oct 13;1(5):1078-1089. Epub 2020 Jun 13.

Pharmacology, Toxicology & Therapeutics University/BHFCentre for Cardiovascular Research, University of Edinburgh Edinburgh UK.

Background: The impact of poison information services on patient care in hospital, particularly decisions on whether to admit patients after initial attendance at an emergency department (ED), is unclear. In the United Kingdom, the vast majority of poisons information is provided by use of the online poisons information database, TOXBASE. We investigated the relationship between rates of hospital access to TOXBASE and rates of poisoning admissions from EDs in England and Wales to begin to address the interactions between use of poisons information and patient management as reflected by hospital activity.

Methods: Data were obtained on attendances and admissions due to poisoning for individual National Health Service (NHS) Trusts in both England and Wales, together with data on the overall number of accesses to TOXBASE for drugs (pharmaceuticals and drugs of abuse), from 2008 to 2015. Rates of TOXBASE access and admissions per poisoning attendance in London were clearly different to the rest of England and Wales; London was therefore analyzed separately. Negative binomial generalized additive models were fit, incorporating an interaction effect, for accesses, attendances and admissions to check for variability according to hospital size. Additional models were then fit to assess whether there was any variation in association of overall TOXBASE use with rates of admission for 6 key drug subgroups: antidepressants, paracetamol, antipsychotics, opioids (including all medicines, but excluding heroin), heroin and non-opioid drugs of abuse.

Results: Rates of TOXBASE use per Trust increased across the study period by 39.3% (95% confidence interval [CI] = 34.1%, 44.8%) in England and 76.9% (24.7%, 151.0%) in Wales, showing an increase in TOXBASE use which was substantially greater than the increase in poisoning attendances. Admission rates exhibited seasonality, with lower rates in January and February, increasing by 2.0% (1.0%, 3.1%) in England and 5.8% (5.5%, 5.9%) in Wales toward the middle of the year. The initial model fit indicated that the average proportion of poisoning patients admitted increased with both increasing attendances and increasing TOXBASE use (England and Wales overall, < 0.0001; England and Wales excluding London, < 0.0001; London, < 0.0001). In England and Wales overall, and in London alone, increased TOXBASE access to non-opioid drugs of abuse advice was associated with a significant decrease in admissions (England and Wales, -0.15% [-0.29%, -0.01%] [ = 0.032]; London, -1.02% [-1.53%, -0.50%] [ < 0.0001]). In contrast, increased access to heroin advice was associated with a significant increase in admissions in London (+2.03% [+0.11%, +3.99%] [ = 0.034]). Increasing access to TOXBASE for paracetamol advice was associated with lower admissions in England and Wales (England and Wales, -0.11% [-0.23%, -0.01%] [ = 0.036]; England and Wales excluding London, -0.18% [-0.30%, -0.06%] [ = 0.001]) but higher admissions in London (+0.52% [+0.03%, +1.01%] [ = 0.035]).

Conclusions: We have shown that greater overall use of TOXBASE by hospitals is associated with a higher proportion of poisoning attendances being admitted. Interestingly, looking at particular drug groups, we found significant associations in both directions between overall TOXBASE use and rates of admission for some drug groups. The current methodology is unable to determine whether such decisions might be appropriate or not. Mixed-methods research is now required to gain a better understanding of how provision of poisons information affects decisions within the ED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/emp2.12116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593423PMC
October 2020

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

EClinicalMedicine 2019 May-Jun;11:11-17. Epub 2019 May 2.

Pharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2019.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610779PMC
May 2019

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

Clin Toxicol (Phila) 2019 Dec 20;57(12):1146-1153. Epub 2019 Mar 20.

NPIS (Birmingham Unit), City Hospital, Birmingham, UK.

Liquid laundry detergent capsules contain concentrated liquid laundry detergent in a water-soluble polyvinyl alcohol membrane. 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. Telephone enquiries to the NPIS and returned questionnaires for these products were analyzed for the period January 2008 to December 2018. 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 ( = 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 ( = 75), stridor ( = 34), CNS depression ( = 22), keratitis/corneal damage ( = 21), coughing ( = 18), conjunctivitis ( = 13), hypersalivation ( = 12), foaming from the mouth ( = 11) and hypoxemia ( = 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2019.1590586DOI Listing
December 2019

Iron overdose - Response.

Clin Toxicol (Phila) 2019 01 3;57(1):72-73. Epub 2018 Sep 3.

f National Poisons Information Service - Newcastle, Regional Drugs & Therapeutics Centre and Medical Toxicology Centre , Newcastle University , Newcastle upon Tyne , UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2018.1493206DOI Listing
January 2019

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

Clin Toxicol (Phila) 2018 11 28;56(11):1098-1106. Epub 2018 Mar 28.

a Department of Pharmacology, Toxicology, and Therapeutics , University/BHF Centre for Cardiovascular Science, University of Edinburgh , Edinburgh , UK.

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. 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. 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) ( < .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  < .0018). No significant differences in symptoms were observed pre-treatment between DFO-treated and untreated groups. No patients died in this cohort. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2018.1455978DOI Listing
November 2018

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

Clin Toxicol (Phila) 2018 06 20;56(6):427-432. Epub 2017 Nov 20.

a NPIS (Birmingham Unit) , City Hospital , Birmingham , UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2017.1393083DOI Listing
June 2018

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

Clin Toxicol (Phila) 2018 05 26;56(5):342-347. Epub 2017 Oct 26.

a National Poisons Information Service (Newcastle Unit), Regional Drug and Therapeutics Centre , Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle , UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2017.1390120DOI Listing
May 2018

Toxicity resulting from exposure to oven cleaners as reported to the UK National Poisons Information Service (NPIS) from 2009 to 2015.

Clin Toxicol (Phila) 2017 Aug 26;55(7):645-651. Epub 2017 Apr 26.

a NPIS (Birmingham Unit) , City Hospital , Birmingham , UK.

Introduction: Oven cleaning products contain corrosive substances, typically sodium or potassium hydroxide.

Objective: To determine the reported toxicity from exposure to oven cleaning products.

Methods: Telephone enquiries to the UK National Poisons Information Service regarding oven cleaning products were analysed retrospectively for the period January 2009 to December 2015.

Results: There were 796 enquiries relating to 780 patients. Ninety-six percent of the products involved in the reported exposures contained sodium hydroxide and/or potassium hydroxide. Ingestion alone (n = 285) or skin contact alone (n = 208) accounted for the majority of cases; inhalation alone (n = 101), eye contact alone (n = 97), and multiple routes of exposure (n = 89) accounted for the remainder. Ninety-five percent of patients exposed by inhalation, 94% exposed dermally and 85% reporting eye exposure, developed features of toxicity. Patients exposed by multiple routes developed symptoms in 70% of cases. Only 103 of the 285 patients ingested oven cleaner directly, whereas 182 patients ingested food they considered to have been contaminated with oven cleaner. In 100 of the 103 direct ingestions where the features and World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score were known, 56 reported symptoms which were minor in 51 cases. The most common features following ingestion were vomiting (n = 26), abdominal pain (n = 22) or pharyngitis (n = 15). Skin burns (n = 91) predominantly involving the hands or arms, occurred in 44% of dermal exposures. Following inhalation, patients frequently developed respiratory features (n = 52) including coughing and chest pain/tightness. Eye pain (n = 43) and conjunctivitis (n = 33) commonly occurred following ocular exposure.

Conclusions: Most (71%) patients exposed to an oven cleaner irrespective of the route of exposure developed features of toxicity, though in most cases only minor features developed; moderate or severe features ensued in ∼4%. Those patients exposed dermally, ophthalmically or by inhalation developed features more frequently (≥85%) than those who ingested a product directly (56%).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2017.1306070DOI Listing
August 2017

Toxicity from fluoropolymer-containing grout, tile and stone floor sealants reported to the UK National Poisons Information Service 2009-2015.

Clin Toxicol (Phila) 2017 Jul 28;55(6):585-588. Epub 2017 Mar 28.

a NPIS (Birmingham Unit) , City Hospital , Birmingham , UK.

Context: Grout, tile and floor stone sealants contain a solvent, a water-repelling agent and in the case of aerosols a propellant. The water-repelling agent used is typically a fluoropolymer resin, a silicon-based resin, or a combination of both.

Objective: To report the clinical course in patients exposed to fluoropolymer-containing sealants referred to the United Kingdom National Poisons Information Service.

Methods: A retrospective analysis was performed of telephone enquiries received between 2009 and 2015.

Results: 101 enquiries involving 96 exposures were received. The majority of the exposures (n = 88) occurred when the sealant was delivered from an aerosol. Twelve patients were exposed occupationally and the remainder were exposed while using the product at home. Eighty-nine exposures were as a result of inhalation alone, two followed ingestion, three skin contact and one eye contact; one involved inhalation and eye contact. All 90 patients exposed by inhalation developed clinical features: 31 had a World Health Organisation/International Programme on Chemical Safety/European Commission/European Association of Poison Centres and Clinical Toxicologists Poisoning Severity Score of 1 (minor toxicity), 51 patients had features of moderate toxicity (PSS 2) and eight were graded PSS 3 (severe poisoning). The most common features were dyspnea (n = 52; 57.8%; 95% CI = 47.0-68.5), chest pain/tightness (n = 34; 37.8%; 95% CI = 27.2-48.4), coughing (n = 27; 30.0%; 95% CI = 20.0-40.0) and sinus tachycardia (n = 11; 12.2%; 95% CI = 4.1-18.2); hypoxemia was present in 20 (22.2%; 95% CI = 13.1-31.4). At the time of the enquiry a chest X-ray had been performed on 15 patients: in eight patients (all of whom were PSS 3) the X-ray was reported as being abnormal and showed bilateral shadowing.

Conclusions: This study demonstrates that if fluoropolymer-containing sealants are inhaled then clinical features may occur and in a small proportion (9%) these features may be severe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650.2017.1296154DOI Listing
July 2017

Serum alkalinisation is the cornerstone of treatment for amitriptyline poisoning.

BMJ Case Rep 2016 Apr 11;2016:10.1136/bcr-2016-214685. Epub 2016 Apr 11.

National Poisons Information Service Edinburgh, NHS Lothian, Edinburgh, UK.

A 28-year-old woman was admitted in a comatose state following ingestion of 5 g of amitriptyline. On arrival, there was intermittent seizure activity and a broad complex tachycardia on the ECG. Immediate resuscitation included 8 mg lorazepam, 2 L crystalloid fluid, 100 mL 8.4% sodium bicarbonate, 2 g of magnesium sulphate and lipid emulsion infusion. Despite this, the broad complex tachycardia persisted with haemodynamic instability. The case was discussed with the National Poisons Information Service, which advised further 8.4% sodium bicarbonate to achieve serum alkalinisation. Following this, the QRS duration reduced and haemodynamic stability was achieved. Serum alkalinisation continued in the intensive treatment unit before the patient was successfully extubated on day 5 and discharged on day 7 with no neurological sequelae. To our knowledge, this case is the largest recorded overdose of amitriptyline to have survived to discharge. The importance of serum alkalinisation in the management of tricyclic antidepressant poisoning is highlighted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2016-214685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840635PMC
April 2016

Disproportionate effect on child admissions of the change in Medicines and Healthcare Products Regulatory Agency guidance for management of paracetamol poisoning: an analysis of hospital admissions for paracetamol overdose in England and Scotland.

Br J Clin Pharmacol 2015 Dec 26;80(6):1458-63. Epub 2015 Oct 26.

Pharmacology, Toxicology and Therapeutics, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.

Objective: The aim of the present study was to assess the effects of the changes in the management of paracetamol overdose recommended by the UK Commission for Human Medicines on rates of hospital admission.

Methods: An interrupted time series analysis was carried out on data for hospital admissions for paracetamol poisoning for England between January 2010 and June 2014, and for Scotland between January 2010 and Sept. 2014. The main outcome measure was admissions to hospital with paracetamol poisoning (T39.1), as defined by first position coding in children and adults.

Results: The time series analysis (Jan 2010 to June 2014) showed that admission rates for paracetamol poisoning were steady from 2010 to the date of change (September 2012), with an estimated 269 [95% confidence interval (CI) 252.5, 285.5] child (0-14 years) and 3541 (95% CI 3454, 3628) adult admissions per month. In September 2013, 12 months after the change, there were an estimated additional 116 [37.3% (95% CI 17.2-67.4)] child and 426 [12.5% (95% CI 4.5-19.6)] adult admissions. Thus, in the year before the change (September 2011 to August 2012) there were 45,181 (3500 child and 41,681 adult) admissions, and in the year after (September 2012 to August 2013) there were 50,198 (4779 child and 45,419 adult) admissions. The overall proportion of child admissions was significantly greater after the change (Chi-square 32.486, P < 0.001), emphasizing the disproportionate effect in children.

Conclusions: Changes to the management guidelines for paracetamol poisoning in September 2012 were rapidly implemented but have particularly increased paediatric hospital admissions for paracetamol poisoning. This impact in children, who are at low risk of mortality from paracetamol toxicity, appears excessive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693484PMC
December 2015

Life-threatening opioid toxicity from a fentanyl patch applied to eczematous skin.

BMJ Case Rep 2015 Apr 29;2015. Epub 2015 Apr 29.

National Poisons Information Service Edinburgh, NHS Lothian, Edinburgh, UK.

A 19-year-old man with a history of eczema was admitted to the emergency department following collapsing at home. The paramedics found him unresponsive with poor respiratory effort and a widespread erythematous rash. Anaphylaxis, thought to be secondary to flucloxacillin he had recently been prescribed, was diagnosed. Epinephrine, steroids and antihistamines were administered without clinical improvement. On arrival to hospital, constricted pupils were noted prompting the emergency physicians to consider opiate toxicity. Intravenous naloxone brought about an immediate recovery. His father subsequently disclosed that he had given his son one of his own fentanyl patches to alleviate the distressing symptoms of eczema. Although the patient had removed the patch prior to collapsing, he had suffered life-threatening opioid toxicity likely due to enhanced opiate absorption through eczematous skin. This case highlights the risks associated with fentanyl patches in patients with chronic skin conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2014-208945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422925PMC
April 2015

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

Br J Clin Pharmacol 2014 Sep;78(3):610-8

NPIS Edinburgh & Royal Infirmary of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243911PMC
September 2014

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

Lancet 2014 Feb 28;383(9918):697-704. Epub 2013 Nov 28.

Emergency Medicine Research Group, Department of Emergency Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(13)62062-0DOI Listing
February 2014

Measurement of renal function in patients with chronic kidney disease.

Br J Clin Pharmacol 2013 Oct;76(4):504-15

National Poisons Information Service Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791974PMC
October 2013

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP).

BMC Pharmacol Toxicol 2013 Apr 4;14:20. Epub 2013 Apr 4.

NPIS Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.

Background: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen.

Methods/design: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course.

Discussion: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk.

Trial Registration: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT01050270.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2050-6511-14-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626543PMC
April 2013

Histamine-induced vasodilatation in the human forearm vasculature.

Br J Clin Pharmacol 2013 Nov;76(5):699-707

NPIS (Edinburgh), Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853529PMC
November 2013

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

BMC Clin Pharmacol 2012 Feb 3;12. Epub 2012 Feb 3.

National Poisons Information Service (Edinburgh), Royal Infirmary of Edinburgh, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1472-6904-12-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293780PMC
February 2012

'Ivory wave' toxicity in recreational drug users; integration of clinical and poisons information services to manage legal high poisoning.

Clin Toxicol (Phila) 2012 Feb 6;50(2):108-13. Epub 2012 Jan 6.

NPIS Edinburgh, Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, 51 Little France Crescent, EH16 4SA.

Background: Novel psychoactive substances or 'legal highs' can be defined as psychoactive substances that have been developed to avoid existing drug control measures. Consistency of name, but with change in the content of the product, may cause harm. This could result in clusters of users being poisoned and developing unexpected physical and psychiatric symptoms. We describe such an event and the clinical phenotypes of a cluster of patients poisoned with a novel psychoactive substance in 'ivory wave' and analyze data from the National Poisons Information Service (NPIS) to estimate use across the United Kingdom. In addition, the likely active ingredient in this cluster of 'ivory wave' poisonings was identified.

Methods: An analysis of consecutive patients attending the Royal Infirmary of Edinburgh emergency department in July and August 2010 with self-reported 'ivory wave' use was performed. Over a similar time frame, poisons enquiries regarding 'ivory wave' to the UK NPIS, by telephone and via the internet-based TOXBASE(®) poisons database ( www.toxbase.org ), were analyzed. A sample of 'ivory wave' powder and biological fluids from poisoned patients were investigated to determine the active ingredient.

Results: Thirty four emergency attendances due to 'ivory wave' toxicity were identified. The mean +/- SD (range) age was 28.6 +/- 7.8 (16-44) years. Patients demonstrated a toxidrome which lasted several days, characterized by tachycardia (65%), tachypnoea (76%), dystonia (18%), rhabdomyolysis (96%), leucocytosis (57%), agitation (62%), hallucinations (50%), insomnia (32%) and paranoia (21%). Enquiries to NPIS suggest that 'ivory wave' poisoning occurred throughout the United Kingdom. A sample of 'ivory wave' powder was analyzed and found to contain desoxypipradrol, which was also identified in biological fluids from 4 out of 5 patients tested.

Discussion: A cluster of cases presenting after use of a novel psychoactive substance was identified in Edinburgh and desoxypipradrol was identified as the likely cause. It was associated with prolonged psychiatric symptoms as a key feature. This chemical was regulated in response to the wider UK outbreak, which NPIS data suggest was geographically widespread but probably short lived.

Conclusion: Novel psychoactive substances can produce significant toxicity and data from poisons centres may be used to indirectly detect new 'legal highs' that are causing clinical toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/15563650.2011.647992DOI Listing
February 2012

Tricyclic antidepressant overdose in a toddler treated with intravenous lipid emulsion.

Pediatrics 2011 Dec 7;128(6):e1628-32. Epub 2011 Nov 7.

Department of Anaesthesia, Craigavon Area Hospital, Portadown, Northern Ireland.

We report a case that involves the use of intravenous lipid emulsion as an antidote for a drug overdose involving a 20-month-old girl who had ingested a potentially lethal amount of the tricyclic antidepressant (TCA) dothiepin. The patient's condition continued to deteriorate despite implementation of standard pediatric treatment recommendations for TCA toxicity. Administration of intravenous lipid emulsion in addition to standard therapy (including sodium bicarbonate) and direct-current cardioversion for ventricular arrhythmia led to a successful outcome. The case report is followed by a review of the current evidence underlying this novel therapy and the background on its use. TCA toxicity is addressed specifically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2011-0867DOI Listing
December 2011

An integrated care pathway improves the management of paracetamol poisoning.

Emerg Med J 2012 Jun 11;29(6):482-6. Epub 2011 May 11.

Clinical Toxicology Unit, Combined Assessment Area, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH 16 4SA, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/emj.2011.111922DOI Listing
June 2012

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

Br J Clin Pharmacol 2011 Jan;71(1):29-33

NPIS Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2125.2010.03808.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018023PMC
January 2011

European Medicines Evaluation Agency bans dextropropoxyphene: a landmark decision for clinical toxicology?

Clin Toxicol (Phila) 2009 Sep;47(8):782-3

Royal Infirmary of Edinburgh, Edinburgh, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15563650903218757DOI Listing
September 2009
-->