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Background The use of disinfectants and alcohol-based hand rubs (ABHR) to prevent COVID-19 transmission increased in the first wave of the infection. To meet the increased demand, the Iranian Ministry of Health issued an emergency use authorization allowing new manufacturers to enter the market, despite the limited capacity for surveillance of these products during COVID-19. Methanol poisoning outbreaks spread rapidly, and more people died from methanol poisoning than COVID-19 in some cities. The aim of this study was to analyze some ABHRs in the Iranian market to see if (a) ABHRs are standard and suitable for hand antisepsis and (b) contained potentially dangerous toxic alcohols. Method Between February and March 2020, 64 brands of ABHR were conveniently collected from pharmacies, supermarkets, and shops selling hygienic products and analyzed using Gas Chromatography. World Health Organization and Food and Drug Administration guidelines were used to define minimum requirements for ABHR. For estimating the risk for acute methanol poisoning, we assumed a serum methanol concentration of 200 mg/L following ABHR ingestion was sufficient to cause intoxication. This threshold concentration would be achieved in an average 75-kg adult after consuming 8000 mg (or eight grams) methanol in 1–2 h. Results The median [IQR] (range) concentration of ethanol, isopropanol, and methanol were 59% v/v [32.2, 68] (0, 99), 0 mg/L [0, 0] (0, 197,961), and 0 mg/L [0, 0] (0, 680,100), respectively. There was a strong negative correlation between methanol and ethanol contents of hand rubbers (r= -0.617, p Conclusion COVID-19 initiated a policy for distribution and use of ABHR with little control. As ABHR and masks are still accepted preventive measures of the disease, non-standard ABHR compositions may increase the population’s risk to both COVID-19 infection and methanol poisoning.

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m(2)]: 91 patients; low-dose [≤0.5 g/m(2)]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

Barium poisoning is rare but potentially severe. We describe a case of acute barium carbonate poisoning with cardiac arrest, managed with intravenous potassium, dialysis and endoscopic removal of retained ceramic glazes.A 38-year-old woman presented with vomiting 90 min after ingesting 3 cups of barium and strontium carbonate. Initial bloods noted potassium 2.8 mmol/L and creatinine 53 μmol/L. Electrocardiogram demonstrated prolonged corrected QT interval 585msec. Initial management included intravenous potassium. Four hours post-ingestion she developed proximal muscle weakness in upper limbs with a potassium of 2.2 mmol/L. At 15 h post-ingestion she developed profound muscle weakness, polymorphic ventricular tachycardia and cardiac arrest. Treatment included defibrillation, endotracheal intubation and continuous veno-venous haemodialysis (CVVHD) for metabolic derangement and enhanced elimination of barium. Chest X-ray 17 h post-ingestion demonstrated a large radio-opaque mass in the stomach, thought to be the ceramic glaze. Endoscopy removed the retained material 41 h post-ingestion. She was extubated 58 h post-ingestion and CVVHD was ceased on day 3. Serum creatinine peaked at 348 μmol/L on day 7, but normalised by discharge. Biphasic barium concentrations were noted, notably 94 μmol/L on admission, 195 μmol/L at 16 h, 95 μmol/L at 20 h, and 193 μmol/L at 30 h post-ingestion.In barium poisoning with hypokalaemia, prompt potassium supplementation is required but rebound hyperkalaemia can occur. Endoscopic removal of ceramic glazes may be useful more than 12 h post-ingestion. Consider extracorporeal methods to enhance barium elimination in severe cases.

Ethylene glycol poisoning manifests as metabolic acidemia, acute kidney injury and death. The diagnosis and treatment depend on history and biochemical tests. Glycolate is a key toxic metabolite that impacts prognosis, but assay results are not widely available in a clinically useful timeframe. We quantitated the impact of serum glycolate concentration for prognostication and evaluated whether more readily available biochemical tests are acceptable surrogates for the glycolate concentration.The objectives of this study are to 1) assess the prognostic value of the initial glycolate concentration on the occurrence of AKI or mortality in patients with ethylene glycol exposure (A systematic review of the literature was performed using Medline/PubMed, EMBASE, Cochrane library, conference proceedings and reference lists. Human studies reporting measured glycolate concentrations were eligible. Glycolate concentrations were related to categorical clinical outcomes (acute kidney injury, mortality), and correlated with continuous surrogate biochemical measurements (anion gap, base excess, bicarbonate concentration and pH). Receiver operating characteristic curves were constructed to calculate the positive predictive values and the negative predictive values of the threshold glycolate concentrations that predict acute kidney injury and mortality. Further, glycolate concentrations corresponding to 100% negative predictive value for mortality and 95% negative predictive value for acute kidney injury were determined.Of 1,531 articles identified, 655 were potentially eligible and 32 were included, reflecting 137 cases from 133 patients for the prognostic study and 154 cases from 150 patients for the surrogate study. The median glycolate concentration was 11.2 mmol/L (85.1 mg/dL, range 0-38.0 mmol/L, 0-288.8 mg/dL), 93% of patients were treated with antidotes, 80% received extracorporeal treatments, 49% developed acute kidney injury and 13% died. The glycolate concentration best predicting acute kidney injury was 12.9 mmol/L (98.0 mg/dL, sensitivity 78.5%, specificity 88.1%, positive predictive value 86.4%, negative predictive value 80.9%). The glycolate concentration threshold for a 95% negative predictive value for acute kidney injury was 6.6 mmol/L (50.2 mg/dL, sensitivity 96.9%, specificity 62.7%). The glycolate concentration best predicting mortality was 19.6 mmol/L (149.0 mg/dL, sensitivity 61.1%, specificity 81.4%, positive predictive value 33.3%, negative predictive value 93.2%). The glycolate concentration threshold for a 100% negative predictive value for mortality was 8.3 mmol/L (63.1 mg/dL, sensitivity 100.0%, specificity 35.6%). The glycolate concentration correlated best with the anion gap (This systematic review demonstrates that the glycolate concentration predicts mortality (unlikely if8 mmol/L [61 mg/dL]). The anion gap is a reasonable surrogate measurement for glycolate concentration in the context of ethylene glycol poisoning. The findings are mainly based on published retrospective data which have various limitations. Further prospective validation studies are of interest.

This case report describes a 31-year-old man with 10 years of cocaine and cannabis dependence who developed reverse Takotsubo cardiomyopathy (rTC), a rare variant of Takotsubo cardiomyopathy. He presented to the Emergency Department (ED) with severe left temporal headache and vomiting which began whilst smoking cannabis and several hours after smoking methamphetamine and using cocaine via insufflation. Computed tomography and angiography of the brain was normal, and the headache resolved with analgesia. Urine drug screen was positive for benzodiazepines, cannabinoids, cocaine, opiates (attributed to morphine administered in ED) and amphetamines. Three hours later he had a seizure and within 10 min developed cardiogenic shock with antero-inferior ST segment depression on electrocardiogram and troponin-T rise to 126 ng/L. Coronary angiography demonstrated normal coronary arteries. Transthoracic echocardiogram demonstrated severely impaired left ventricular (LV) systolic function with ejection fraction 15–20% and hypokinesis sparing the apex. Thyrotoxicosis, nutritional, vasculitic, autoimmune and viral screens were negative. Cardiac magnetic resonance imaging demonstrated severe LV functional impairment with dilated and hypocontractile basal segments, and T2 hyperintensity consistent with myocardial oedema and rTC. He received supportive management. Proposed mechanisms of rTC include catecholamine cardiotoxicity and coronary artery vasospasm. In this case, multiple insults including severe headache, cannabis hyperemesis and cocaine and methamphetamine-induced serotonin toxicity culminated in a drug-induced seizure which led to catecholamine cardiotoxicity resulting in rTC. Clinicians should be cognizant of stress cardiomyopathy as a differential diagnosis in patients with substance use disorders.

Adulteration, substitution or contamination of illicit substances can have clinically significant implications when other illicit substances are included. Such circumstances can present as clusters of poisonings, including severe toxicity and death following exposure to unexpected illicit substances. We report a cluster of laboratory-confirmed lysergic acid diethylamide (LSD) in a powder that was sold as cocaine and used recreationally.The Prescription, Recreational and Illicit Substance Evaluation (PRISE) program established by the New South Wales Ministry of Health includes State-based hospital toxicology services, Poisons Information Centre, ForensicAnalytical Science Service and emergency services to identify clusters of severe and unusual toxicity associated with substance use. PRISE criteria include a known cluster (geographically or situationally related) of people with acute severe toxicity, especially when accompanied by a toxidrome that is inconsistent with the history of exposure. A timely comprehensive drug screen and quantification is performed in eligible cases and the results are related to the clinical features. The need for a public health response is then considered. Four individuals inhaled a white powder that was sold as cocaine and developed severe toxicity that was not consistent with cocaine which prompted transfer to hospital for further management.LSD was confirmed in four subjects, and the concentrations in 3 of the individuals were 0.04-0.06 mg/L which are among the highest reported in the literature. Common clinical features were hallucinations, agitation, vomiting, sedation, hypertension, and mydriasis. One subject required intubation and admission to the intensive care unit, two required overnight admission, and the fourth was discharged following oral diazepam after observation. No subject suffered persistent injury.A close working relationship between pre-hospital emergency services, hospital-based clinical services, public health authorities, and analytical laboratories appears to be advantageous. Favourable clinical outcomes are observed from LSD poisoning despite high exposures with good supportive care.

High dose insulin (HDI) therapy for cardiogenic shock from acute poisoning can be complicated by treatable hypoglycemia which persists following poisoning recovery. Glucose requirements post-HDI reflect supraphysiological insulin plasma concentration. A publication reported a patient treated with HDI with plasma insulin concentrations1000 µU/mL and elimination half-life 10-18 h requiring intravenous glucose replacement for5 days. We report two cases treated with HDI (Actrapid; soluble or regular insulin) with shorter elimination half-lives.A man ingesting diltiazem received HDI for approximately 60 h (maximum dose 10 U/kg/h) and supplemental intravenous dextrose for 44 h post-HDI. Post-HDI the maximum measured plasma insulin concentration was 6345 µU/mL and elimination half-life 5.5 h. A man ingesting propranolol received HDI for approximately 12 h (maximum dose 1.5 U/kg/h) and supplemental intravenous dextrose for 4 h post-HDI. Post-HDI the maximum measured plasma insulin concentration was 368 µU/mL and elimination half-life 2.2 h.Markedly different insulin pharmacokinetics post-HDI is observed in two cases and a previously published report, and factors contributing to the interpatient differences are poorly defined. This pharmacokinetic variability impacts on the severity and duration of treatable hypoglycemia post-HDI. Analytical factors impacting on the measured plasma insulin concentrations include appropriate sample dilution and differing analytical specificity for the type of insulin.

Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning.We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods.A total of 83 publications (6Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.

Purpose of review There is controversy regarding the impact of hyperuricemia on the progression of chronic kidney disease (CKD), and gout remains sub optimally managed in this population. We discuss the prescribing of drugs for the treatment of gout in patients with CKD. Recent findings There is a lack of consensus from expert guidelines, and prescribers have concerns regarding the risk of adverse reactions from medicines used to treat gout. These situations appear to contribute to suboptimal management of gout in this cohort. Recent data have challenged the role of urate lowering therapy (ULT) in the management of asymptomatic hyperuricemia in CKD. Summary ULT should be commenced in all patients with severe, recurrent disease, tophaceous gout and evidence of joint damage. Most international guidelines recommend a treat-to-target approach for the management of gout. In CKD, ULT should be started at low dose with up titration adjusted to serum urate levels, rather than being based on the creatinine clearance. If patients fail first-line therapy, alternative agents are utilized, the specific agent depending on ease of access, burden of disease and other comorbidities. This approach should be incorporated into routine practice to ensure optimal treatment of gout in CKD. More research is required to investigate whether treatment of asymptomatic hyperuricemia has clinical benefits.

Rationale Regular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal. Objectives To examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020. Methods We retrospectively reviewed records (01 January 2017–31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p Results We identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated. Conclusions This study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required.

SUMMARY Proteinuria, in particular albuminuria, is a potentially significant modifiable risk factor for cardiovascular disease and the progression of kidney disease. Current treatment guidelines for albuminuria recommend a single renin–angiotensin–aldosterone inhibitor. This can be an ACE inhibitor or an angiotensin receptor antagonist. The routine use of combined renin–angiotensin–aldosterone inhibition for albuminuria is not supported by current evidence. Combination therapy is associated with higher rates of adverse events such as hyperkalaemia and progressive renal impairment.

Poisoning caused by a large range of drugs and chemicals can induce metabolic complications via a large number of mechanisms. Some metabolic complications are life-threatening but all require careful assessment, appropriate monitoring and consideration of treatment. Prompt diagnosis and management reduce morbidity and mortality. Treatment may be targeted to the specific poisoning, and may be time-critical, or can follow similar approaches to those of general and acute medicine. This review introduces metabolic complications associated with sodium, potassium, metabolic acidosis, rhabdomyolysis and methaemoglobinaemia.

Introduction: Accidental pediatric liquid paracetamol exposure is common. Most children do not require treatment with acetylcysteine and acute liver injury is rare.Case report: An otherwise well 3-...

Drs Lai, Graudins and Wong highlight the potential contribution of cardiorespiratory comorbidities on the raised NT-proBNP in a case of acute eucalyptus oil poisoning [1]. We similarly considered t...

Context: 1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) analogue with a similarly narrow therapeutic window that is becoming a more common cause of recreational overdose. Reports of confirmed exposures are limited.Case details: A 44 year-old man who had consumed alcohol subsequently became unconscious after ingesting what was thought to be GHB. The presentation was not entirely consistent with GHB poisoning, including a longer duration of unconsciousness and features that mimicked toxic alcohol exposure including a high anion gap metabolic acidosis (HAGMA) and osmol gap. The patient was treated supportively with intubation, haemodiafiltration and intravenous ethanol until the diagnosis was refined using specific laboratory testing. The concentration of 1,4-BD was the highest reported in the literature and the outcome favourable.Discussion: This case highlights pharmacokinetic issues peculiar to 1,4-BD, including the interaction with ethanol which delays the onset of psychoactive effects from 1,4-BD's metabolite GHB, and dose-dependent pharmacokinetics. In overdose, 1,4-BD can induce a HAGMA and other features of toxic alcohol poisoning. Managing an unconscious patient with these features can prompt certain treatments until the diagnosis is refined, which can require specific laboratory testing to identify the culprit. The actual risk of toxic alcohol and other causes is adjusted on a case-by-case basis from the history of exposure and local epidemiology of substance use and poisoning.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning.Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria.Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented.Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

Staphylococcus aureus bacteraemia (SAB) is often a complication of injecting drug use, and is associated with high morbidity and mortality. This article reports the first audit of inpatient parenteral treatment of SAB completion among people who inject drugs (PWID) in Australia. Of 198 patients admitted with SAB, 106 were analysed. Twelve PWID had an inpatient stay

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.

There is controversy regarding the impact of hyperuricemia on the progression of chronic kidney disease (CKD), and gout remains sub optimally managed in this population. We discuss the prescribing of drugs for the treatment of gout in patients with CKD.There is a lack of consensus from expert guidelines, and prescribers have concerns regarding the risk of adverse reactions from medicines used to treat gout. These situations appear to contribute to suboptimal management of gout in this cohort. Recent data have challenged the role of urate lowering therapy (ULT) in the management of asymptomatic hyperuricemia in CKD.ULT should be commenced in all patients with severe, recurrent disease, tophaceous gout and evidence of joint damage. Most international guidelines recommend a treat-to-target approach for the management of gout. In CKD, ULT should be started at low dose with up titration adjusted to serum urate levels, rather than being based on the creatinine clearance. If patients fail first-line therapy, alternative agents are utilized, the specific agent depending on ease of access, burden of disease and other comorbidities. This approach should be incorporated into routine practice to ensure optimal treatment of gout in CKD. More research is required to investigate whether treatment of asymptomatic hyperuricemia has clinical benefits.

This study evaluated the ability of a pilot therapeutic drug monitoring (TDM) Advisory Service to facilitate vancomycin therapeutic target attainment within a real-world clinical setting. The Service provided area under the concentration-time curve (AUC)-guided vancomycin dose recommendations, using Bayesian forecasting software and clinical expertise, to prescribers at an Australian hospital. A retrospective audit of intravenous vancomycin therapy (> 48 hours) in adults (≥ 18 years old) was undertaken over a 54-month period to evaluate attainment of established vancomycin pharmacokinetic/pharmacodynamic targets (AUC over 24 hours / minimum inhibitory concentration: 400-600) before (36-month period) and after (18-month period) Service implementation. Interrupted time series analysis was employed to evaluate monthly measures of the median proportion of therapy spent within the target range. Indices of time to target attainment were also assessed before and after Service implementation. The final cohort comprised 1,142 courses of vancomycin (816 patients); 835 courses (596 patients) and 307 courses (220 patients) administered before and after Service implementation, respectively. Prior to piloting the Service, the median proportion of time in the target range was 40.1% (95% CI, 34.3-46.0%); this increased by 10.4% (95% CI, 1.2-19.6%, P = 0.03) after the Service, and was sustained throughout the post-Service evaluation period. Post-Service target attainment at 48-72 hours after initiation of therapy was increased (7.8%, 95% CI, 1.3-14.3%, P = 0.02). The findings of this study provide evidence that a consultative TDM Service can facilitate attainment of vancomycin therapeutic targets; however, optimization of the Service may further improve the use of vancomycin.

BACKGROUND: Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs. METHODS: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. RESULTS: A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug. CONCLUSIONS: On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.

SUMMARY Drugs excreted by the kidney require dose reduction in chronic kidney disease. This adjustment depends on the severity of the disease and what proportion of the drug is eliminated by the kidneys The estimated glomerular filtration rate can generally be used to guide dose adjustment in patients with stable kidney function. However, the formula can be misleading in some patient subsets and other approaches are required At extremes of body mass, the estimated glomerular filtration rate can under- or overestimate kidney function. It may need to be adjusted for body surface area, particularly for drugs with a narrow therapeutic range or requiring a minimum concentration to be effective. Close monitoring of drug effect and toxicity is also needed and can be supported by therapeutic drug monitoring For short courses of drugs with a wide therapeutic index, dose adjustment may not be needed Alternative methods for quantifying kidney function include the Cockcroft-Gault formula (estimates creatinine clearance) or direct measures of glomerular filtration rate using exogenous isotope compounds. These are not commonly required

Nausea and vomiting are common symptoms with many possible causes, including the adverse effects of drugs. If a drug is indicated, the cause guides the choice of antiemetic drug The main antiemetic classes include antagonists of the serotonin, dopamine, histamine, muscarinic and neurokinin systems, corticosteroids and benzodiazepines. Some antiemetics appear more effective for specific indications Serotonin and neurokinin antagonists, such as ondansetron and aprepitant, are highly effective in treating chemotherapy-induced nausea and vomiting. Metoclopramide and antihistamines are first-line options for nausea and vomiting in pregnancy Serotonin antagonists and some dopamine antagonists, such as metoclopramide, can prolong the QT interval on the ECG. Dopamine antagonists can cause extrapyramidal adverse effects, particularly in children

AIMS: To assess recommendations provided by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup on extracorporeal toxin removal (ECTR) in lithium poisoning. METHODS: Retrospective assessment in a 128 lithium‐poisoned patient cohort previously used to identify ECTR initiation criteria that could improve outcome (Paris criteria). ECTR requirement using EXTRIP criteria was compared to the actual practice or if Paris criteria were used. The potential impact on outcome if these different criteria were used was investigated. RESULTS: Using the recommended (Rec‐EXTRIP) or recommended + suggested (All‐EXTRIP) EXTRIP criteria, ECTR would have been indicated in more patients than was actually done (P < .001), or if Paris criteria were used (P < .01). The non‐actually ECTR‐treated patients fulfilling Rec‐EXTRIP or All‐EXTRIP criteria had shorter intensive care unit stay (P < .05) and no significant increase in fatalities and neurological impairment on discharge in comparison to the actually ECTR‐treated patients. ECTR requirements using EXTRIP vs Paris criteria were not concordant (P < .001). In the non‐actually ECTR‐treated patients, 31/106 and 55/106 patients fulfilled Rec‐EXTRIP or All‐EXTRIP but not Paris criteria, respectively. Those patients had longer stay (P < .01) but no worse neurological impairment on discharge than the patients not fulfilling any of these criteria (50/106 and 26/106, respectively). In the non‐actually ECTR‐treated patients, 7/106 fulfilled Paris but not Rec‐EXTRIP criteria. Those patients had longer stay (P < .05) and worse neurological impairment on discharge (P < .01) than the 50/106 patients not fulfilling any of these criteria. CONCLUSION: In this cohort of lithium poisonings, EXTRIP criteria may lead to more ECTR than actually performed or if the Paris criteria were used, with no demonstrated improvement in outcome.

Historically, the clinical application of extracorporeal treatments (ECTRs), such as hemodialysis or hemoperfusion, was first intended for poisoned patients. With time, ECTRs were used almost indiscriminately to facilitate the elimination of many poisons, albeit with uncertain clinical benefit. To determine the precise role of ECTRs in poisoning situations, multiple variables need to be considered including a careful risk assessment, the poison's characteristics including toxicokinetics, alternative treatments, the patient's clinical status, and intricacies of available ECTRs, all of which are reviewed in this article. Recently, evidence-based and expert opinion-based recommendations from the EXTRIP workgroup were also published to help minimize the knowledge gap in this area.

A change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug's properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.

Current treatments for antibody-mediated rejection (AMR) in kidney transplantation are based on low-quality data from a small number of controlled trials. Novel agents targeting B cells, plasma cells, and the complement system have featured in recent studies of AMR.We conducted a systematic review and meta-analysis of controlled trials in kidney transplant recipients using Medline, EMBASE, and CENTRAL from inception to February 2017.Of 14 380 citations, we identified 21 studies, including 10 randomized controlled trials, involving 751 participants. Since the last systematic review conducted in 2011, we found nine additional studies evaluating plasmapheresis + intravenous immunoglobulin (IVIG) (two), rituximab (two), bortezomib (two), C1 inhibitor (two), and eculizumab (one). Risk of bias was serious or unclear overall and evidence quality was low for the majority of treatment strategies. Sufficient RCTs for pooled analysis were available only for antibody removal, and here there was no significant difference between groups for graft survival (HR 0.76; 95% CI 0.35-1.63; P = 0.475). Studies showed important heterogeneity in treatments, definition of AMR, quality, and follow-up. Plasmapheresis and IVIG were used as standard-of-care in recent studies, and to this combination, rituximab seemed to add little or no benefit. Insufficient data are available to assess the efficacy of bortezomib and complement inhibitors.Newer studies evaluating rituximab showed little or no difference to early graft survival, and the efficacy of bortezomib and complement inhibitors for the treatment of AMR remains unclear. Despite the evidence uncertainty, plasmapheresis and IVIG have become standard-of-care for the treatment of acute AMR.