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INTRODUCTION: Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia. METHODS AND ANALYSIS: Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes. ETHICS AND DISSEMINATION: This study received ethical approval from the St Vincent's Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience. TRIAL REGISTRATION NUMBER: ACTRN12621001729819.
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Analgésicos Opioides , Estudios de Factibilidad , Hidromorfona , Trastornos Relacionados con Opioides , Humanos , Hidromorfona/administración & dosificación , Hidromorfona/uso terapéutico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Australia , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Tratamiento de Sustitución de Opiáceos/métodos , Tratamiento de Sustitución de Opiáceos/economíaRESUMEN
AIMS: Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. METHODS: Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital-based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46-82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost-reduction in patient sub-populations. CONCLUSIONS: Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital-based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions.
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Análisis Costo-Beneficio , Monitoreo de Drogas , Humanos , Monitoreo de Drogas/economía , Monitoreo de Drogas/métodos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , HospitalesRESUMEN
INTRODUCTION: The global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine. METHODS: This is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given. RESULTS: There were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures. DISCUSSION: Increasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness. CONCLUSION: Relatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful.
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Alucinógenos , Centros de Control de Intoxicaciones , Alucinógenos/envenenamiento , Humanos , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estudios Retrospectivos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Adulto Joven , Adolescente , Psilocibina/envenenamiento , Dietilamida del Ácido Lisérgico/envenenamiento , Nueva Gales del Sur , Banisteriopsis , Anciano , NiñoRESUMEN
OBJECTIVES: In overdose, gamma-hydroxybutyrate (GHB) and its precursors can cause decreased levels of consciousness, coma and death. Here, we aim to describe reported exposure to GHB at four EDs in Sydney, New South Wales (NSW), Australia. METHODS: We searched the ED databases of four Sydney metropolitan hospitals for presentations relating to GHB exposure between 2012 and 2021. We calculated annual number of presentations stratified by hospital, age, sex, mode of arrival and triage category. RESULTS: A total of 3510 GHB-related presentations to ED were recorded across the four hospitals. Data for all hospitals were only available from 2015 onwards and between 2015 and 2021; there was a 114% increase in annual presentations (from 228 to 487). Males represented 68.7% of all presentations and the median age was 31 years (range 16-74 years). There was an increase in the proportion of female presentations between 2012 and 2021 (from 27.9% to 37.9%) along with the severity of presentation over the same period, with the proportion of presentations with a triage category 1 increasing from 19.7% to 34.5%. CONCLUSIONS: Increases in recorded absolute number and severity of GHB-related presentations to Sydney EDs are a major public health concern. There may also be shifts in the demographics of those with GHB-related presentations. Renewed efforts are required to understand the drivers of these increases to optimally target harm reduction approaches.
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Servicio de Urgencia en Hospital , Oxibato de Sodio , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Servicio de Urgencia en Hospital/tendencias , Adolescente , Anciano , Sobredosis de Droga/epidemiologíaRESUMEN
INTRODUCTION: Orphenadrine overdoses can cause antimuscarinic toxicity, respiratory failure, refractory seizures and cardiotoxicity. The dose-toxicity relationship is poorly defined. Orphenadrine is marketed as immediate and sustained release formulations, and it is not known how the formulation impacts on toxicity. We determined the clinical toxicity of orphenadrine in patients referred to a regional poisons centre. METHODS: Retrospective case series of patients in New South Wales with orphenadrine deliberate self-poisoning from January 2016 to April 2022 referred to the New South Wales Poisons Information Centre. Demographics, history of exposure, treatment and outcomes were extracted from clinical databases. Receiver-operating characteristic curves were constructed to determine thresholds predicting toxicity. RESULTS: Forty-eight patients were identified, with information on clinical outcomes in 46 patients and doses in 41 patients. All patients were older than 12 years. The median orphenadrine dose was 770 mg (range 210-10,000 mg), 59 per cent as the immediate release formulation, and 67 per cent reported coingestants. Doses of sustained release formulations were significantly greater than immediate release formulations, median 2,750 mg versus 595 mg. Common clinical features were drowsiness (59 per cent), sinus tachycardia (37 per cent) and confusion (33 per cent). Three patients had mild hypotension, three were intubated for coma, and two had seizures; no patients suffered ventricular dysrhythmias. All patients survived, with 75 per cent being medically cleared within 24 hours of presentation. A dose-toxicity relationship was observed, but conclusions are limited by the small number of cases with moderate or severe toxicity. DISCUSSION: All patients survived, and severe cardiac and neurological toxicity were not observed. This contrasts to published case reports noting severe poisoning at similar or lower doses. Formulation may have an impact on outcomes, with lesser toxicity from sustained release products. CONCLUSIONS: Orphenadrine doses up to 10 g were associated with antimuscarinic toxicity and sedation, but not severe cardiotoxicity. More research exploring the effect of dose and formulation on outcomes is required.
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Sobredosis de Droga , Orfenadrina , Centros de Control de Intoxicaciones , Humanos , Estudios Retrospectivos , Femenino , Masculino , Centros de Control de Intoxicaciones/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Orfenadrina/envenenamiento , Intento de Suicidio , Niño , Nueva Gales del Sur , Preparaciones de Acción Retardada , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Muscarínicos/envenenamiento , Anciano , Relación Dosis-Respuesta a DrogaRESUMEN
Vancomycin's widespread use as the mainstay antibiotic against methicillin-resistant Staphylococcus aureus infections is complicated by its narrow therapeutic index. Therapeutic drug monitoring using area under the concentration-time curve (AUC)-guided dosing is recommended to optimize therapy and prevent vancomycin-associated nephrotoxicity (VAN). In 2018, a consultative therapeutic drug monitoring Advisory Service (the Service) was piloted at an Australian hospital to enable AUC-guided vancomycin dosing. This study sought to compare the incidence of VAN pre- and post-Service implementation. A 4-year retrospective observational study of intravenous vancomycin therapy (greater than 48 hours) in adults (aged 18 years or older), spanning 3 years before and 1-year after implementation of the Service was undertaken. Nephrotoxicity was defined as an increase in serum creatinine concentrations of 26.5 µmol/L or greater or 50% or more from baseline, on 2 or more consecutive days. Univariate analysis was performed to compare patients before and after implementation, and with and without VAN. Independent factors associated with VAN were identified using a multivariate model. In total, 971 courses of vancomycin therapy, administered to 781 patients, were included: 764 courses (603 patients) before implementation and 207 courses (163 patients) after implementation. The incidence of VAN decreased by 5% after Service implementation (15% before implementation vs 10% after implementation; P = .075). Independent factors associated with VAN were sepsis, heart failure, solid-organ transplant, concomitant piperacillin-tazobactam, and average vancomycin AUC during therapy. In conclusion, there was a nonsignificant trend toward a reduced incidence of VAN after the Service. Larger prospective studies are needed to confirm the efficacy of the Service.
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Lesión Renal Aguda , Staphylococcus aureus Resistente a Meticilina , Adulto , Humanos , Vancomicina , Monitoreo de Drogas , Lesión Renal Aguda/inducido químicamente , Australia/epidemiología , Antibacterianos/efectos adversos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning. METHODS: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry. RESULTS: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h. DISCUSSION: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations. CONCLUSIONS: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.
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Acidosis , Lesión Renal Aguda , Mioclonía , Papaver , Masculino , Humanos , Animales , Ratas , Tebaína/análisis , Morfina , Papaver/química , Toxicocinética , Australia , Semillas/química , Té , Lesión Renal Aguda/inducido químicamente , Vómitos/inducido químicamenteRESUMEN
INTRODUCTION: Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate thebaine has strychnine-like properties, but there is limited literature describing human thebaine poisoning. We describe a cluster of acute thebaine poisoning in people ingesting tea made using poppy seeds with high thebaine content that entered the Australian food supply chain. METHODS: This is an observational study of patients poisoned after drinking poppy seed tea. Cases were identified by three prospective toxicovigilance systems: the Emerging Drug Network of Australia collaboration, the New South Wales Prescription, Recreational and Illicit Substance Evaluation program, and the Emerging Drugs Network of Australia Victoria study. We report characteristics of clinical toxicity in cases with reported ingestion of poppy seed tea and analytical confirmation of thebaine exposure. RESULTS: Forty cases presenting with multi-system toxicity following poppy seed tea ingestion were identified across seven Australian states/territories from November 2022 to January 2023. Blood testing in 23 cases confirmed high thebaine concentrations. All 23 were male (median age 35, range 16-71 years). All patients experienced muscle spasms. Rigidity was described in nine, convulsions in six, while rhabdomyolysis, acute kidney injury, and metabolic acidosis occurred in five patients. There were two cardiac arrests. The thebaine median admission blood concentration was 1.6 mg/L, with a range of 0.1-5.6 mg/L, and was the dominant opium alkaloid in all samples. Convulsions, acute kidney injury, metabolic acidosis, and cardiac arrest were associated with increasing median thebaine concentrations. Four patients were managed in the Intensive Care Unit, with two receiving continuous kidney replacement therapy (one also received intermittent haemodialysis) for kidney injury. There was one death. CONCLUSIONS: Thebaine toxicity, like strychnine poisoning, resulted in neuromuscular excitation characterized by muscle spasm, rigidity, and convulsions. Severe toxicity, including acute kidney injury, metabolic acidosis, and cardiac arrest, appears dose-dependent.
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Acidosis , Lesión Renal Aguda , Paro Cardíaco , Papaver , Animales , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Tebaína/análisis , Opio , Estudios Prospectivos , Estricnina , Morfina , Codeína , Semillas/química , Convulsiones , Té , VictoriaRESUMEN
BACKGROUND: Gamma-hydroxybutyrate (GHB) is used at disproportionately high rates within sexuality and gender diverse communities and carries a high risk of overdose. GHB overdose can result in death. Internationally, recent increases in GHB overdoses have been observed. Coronial reviews of GHB-related death highlight the pivotal roles that bystanders to GHB overdose play in preventing fatality. No research has examined, in detail, how bystanders respond to GHB overdose. This qualitative study was conducted among people who use GHB and explored how they responded upon witnessing a GHB overdose experienced by someone else. METHODS: Interviews were conducted with 31 sexuality and gender diverse Australian residents reporting three or more occasions of GHB use in the previous 12 months. Participants were asked questions about witnessed GHB overdose, their actions and decision-making processes throughout overdose. Data were analysed thematically. RESULTS: Participants described witnessing GHB overdose, commonly in private settings involving sexualized GHB use. Variable definitions of GHB overdose were reported, ranging from GHB-induced symptoms of distress to comatose intoxication. Drastic actions to keep someone alert and responsive post-GHB ingestion were reported; these included the administration of stimulant substances and citrus. Decisions to call or not call for emergency medical services (EMS) were influenced by many circumstantial variables. In most instances, an EMS call was resisted and response practices deviated from established first aid protocols. CONCLUSIONS: GHB overdose prevention and response training programs targeting people who use GHB are urgently required. These education interventions ought to address inaccuracies that inform street remedies for GHB overdose, teach people how to safely check breathing and response, promote basic first aid principles and address barriers to contacting EMS.
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Sobredosis de Droga , Trastornos Mentales , Oxibato de Sodio , Humanos , Australia , Sobredosis de Droga/prevención & control , ActitudRESUMEN
AIM: Iterative approaches to vancomycin dosing (e.g., dosing when trough concentrations <15-20 mg/L) can be inadequate. Computer-guided dosing may be superior but has not been evaluated in patients with kidney failure receiving replacement therapy. We evaluated vancomycin concentrations using a hospital protocol and a pharmacokinetic software. We measured vancomycin clearance by the FX8 low-flux filter because data are absent. METHODS: We retrospectively reviewed records of adults with kidney failure requiring replacement therapy receiving vancomycin and dialysed with the FX8 low-flux filter, and calculated the proportion of pre-dialysis concentrations that were within, above or below a specified range. One and two-compartment models in the pharmacokinetic software were assessed by computing mean prediction error (MPE) and root mean square error (RMSE) of observed versus predicted concentrations. Vancomycin extracorporeal clearance was prospectively determined using the extraction method. RESULTS: In 24 patients (34 courses; 139 paired observed and predicted concentrations), 62/139 (45%) pre-dialysis concentrations were 15-25 mg/L, 29/139 (21%) were above, and 48/139 (35%) were below. MPE for the one-compartment model was -0.2 mg/L, RMSE 5.3 mg/L. MPE for the two-compartment model was 2.0 mg/L, RMSE 5.6 mg/L. Excluding the first paired concentrations, the subsequent MPE (n = 105) using one-compartment model was -0.5 mg/L, RMSE 5.6 mg/L. The MPE for the two-compartment model was 2.1 mg/L, RMSE 5.8 mg/L. The median extracorporeal clearance was 70.7 mL/min (range: 10.3-130.3; n = 22). CONCLUSIONS: Vancomycin dosing was suboptimal and the pharmacokinetic software was not sufficiently predictive. These may improve with a loading dose. The substantial removal of vancomycin by low-flux filters is not accounted for by the models tested.
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Insuficiencia Renal , Vancomicina , Adulto , Humanos , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Diálisis Renal/métodos , Insuficiencia Renal/tratamiento farmacológicoRESUMEN
INTRODUCTION: Metformin-associated lactic acidosis is a well-described and commonly encountered condition associated with significant morbidity and mortality. Patients with metformin-associated lactic acidosis are frequently managed in the intensive care unit with supportive care, including volume resuscitation and consideration of an extracorporeal treatment to correct metabolic acidemia and remove metformin and lactate. EXTRACORPOREAL TREATMENTS IN POISONING WORKGROUP: The Extracorporeal Treatments in Poisoning Workgroup published evidence-based consensus recommendations in 2015 regarding the use of extracorporeal treatment in metformin toxicity. These recommendations list both clinical and biochemical indications, and they outline the rationale and evidence supporting each recommendation. NEW RESEARCH SINCE RECOMMENDATIONS WERE PUBLISHED: Subsequent publications have provided new information regarding metformin-associated lactic acidosis and its treatment. A retrospective study showed that patients who did not meet the Extracorporeal Treatments in Poisoning Workgroup criteria for initiation of an extracorporeal treatment had a 100% survival. In patients who met the criteria, survival was approximately 75%; only 66% of these patients received an extracorporeal treatment, and this treatment did not appear to impact survival. Two other retrospective studies in patients diagnosed with metformin-associated lactic acidosis noted that extracorporeal treatments did not improve survival. However, those who received an extracorporeal treatment were more severely ill, potentially supporting a benefit from this intervention. A systematic review of patients receiving continuous kidney replacement therapy identified an overall survival that was higher than the overall survival in patients included in the Workgroup publication. This led the authors to suggest that intermittent hemodialysis may not be the preferred treatment for metformin toxicity. However, a closer look at the Workgroup data identified improved survival with each decade since the initial reports in the 1970s. Furthermore, there are multiple reports of persistent metformin-associated lactic acidosis that did not improve with standard continuous kidney replacement therapy, prompting an increase in the dosage of the extracorporeal treatment. The data supporting these observations are largely derived from retrospective studies, which have inherent biases, so prospective studies are required. PRESCRIBING EXTRACORPOREAL TREATMENTS FOR PATIENTS WITH METFORMIN POISONING: Case-based decision-making is always necessary, but in general, we continue to follow the Extracorporeal Treatments in Poisoning Workgroup criteria because a convincing reason for changing these has not yet been presented. This includes the use of intermittent hemodialysis where possible, particularly in cases of severe poisoning. For patients with less severe poisoning or when intermittent hemodialysis is not readily available, it is reasonable to trial continuous modalities with careful observation for deterioration.
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Acidosis Láctica , Acidosis , Sobredosis de Droga , Metformina , Intoxicación , Humanos , Estudios Retrospectivos , Sobredosis de Droga/terapia , Diálisis Renal , Intoxicación/terapia , HipoglucemiantesRESUMEN
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 < 0.001). Almost 47% of ABHRs complied with minimum standards. In 12.5% of ABHRs, high concentrations of methanol were observed, which have no antiseptic properties but could cause acute methanol poisoning if ingested. 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.
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2-Propanol , COVID-19 , Estados Unidos , Adulto , Humanos , Irán/epidemiología , Estudios Transversales , Metanol , Desinfección de las Manos/métodos , Etanol/químicaRESUMEN
Poisoning occurs after exposure to any of a number of substances, including medicines, which can result in severe toxicity including death. The nephrologist may be involved in poisonings that cause kidney disease and for targeted treatments. The overall approach to the poisoned patient involves the initial acute resuscitation and performing a risk assessment, whereby the exposure is considered in terms of the anticipated severity and in the context of the patient's status and treatments that may be required. Time-critical interventions such as gastrointestinal decontamination ( e.g. , activated charcoal) and antidotes are administered when indicated. The nephrologist is usually involved when elimination enhancement techniques are required, such as urine alkalinization or extracorporeal treatments. There is increasing data to guide decision making for the use of extracorporeal treatments in the poisoned patient. Principles to consider are clinical indications such as whether severe toxicity is present, anticipated, and/or will persist and whether the poison will be significantly removed by the extracorporeal treatment. Extracorporeal clearance is maximized for low-molecular weight drugs that are water soluble with minimal protein binding (<80%) and low endogenous clearance and volume of distribution. The dosage of some antidotes ( e.g. , N-acetylcysteine, ethanol, fomepizole) should be increased to maintain therapeutic concentrations once the extracorporeal treatment is initiated. To maximize the effect of an extracorporeal treatment, blood and effluent flows should be optimized, the filter with the largest surface area selected, and duration tailored to remove enough poison to reduce toxicity. Intermittent hemodialysis is recommended in most cases when an extracorporeal treatment is required because it is the most efficient, and continuous kidney replacement therapy is prescribed in some circumstances, particularly if intermittent hemodialysis is not readily available.
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Intoxicación , Venenos , Humanos , Antídotos/uso terapéutico , Carbón Orgánico/uso terapéutico , Acetilcisteína/uso terapéutico , Etanol , Intoxicación/diagnóstico , Intoxicación/terapiaRESUMEN
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
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Antídotos , Intoxicación , Humanos , Antídotos/uso terapéutico , Fomepizol , Etanol , Diálisis Renal/métodos , Glicolatos , Glicol de Etileno , Intoxicación/terapiaRESUMEN
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 < 0.2) with features of delirium and DAMA. 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.
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Delirio , Oxibato de Sodio , Síndrome de Abstinencia a Sustancias , Humanos , Femenino , Masculino , Oxibato de Sodio/efectos adversos , Estudios Retrospectivos , Baclofeno/uso terapéutico , Pacientes Internos , Estudios Prospectivos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Hospitales Urbanos , Diazepam , Delirio/tratamiento farmacológico , Delirio/epidemiología , Registros Médicos , 4-Butirolactona/uso terapéuticoRESUMEN
INTRODUCTION: Management of a withdrawal syndrome following cessation of regular gamma-hydroxybutyrate (GHB) use, and its precursors, can represent a clinical challenge due to rapid onset delirium and/or seizures. Severe GHB withdrawal can be characterised by persistent or worsening features despite increasing benzodiazepine doses and regular baclofen. Barbiturates, such as phenobarbital, are an appealing option in this context due to their unique GABA-A receptor action. CASE SERIES: This series describes the use of phenobarbital in 13 cases, 12 patients, across two hospitals in Sydney, Australia, with persistent or progressive GHB withdrawal despite benzodiazepine-based management. A median cumulative dose of oral diazepam prior to commencing phenobarbital was 120 mg (range 80-255 mg). The median time from the last GHB use to the first dose of phenobarbital was 24 h (range 7-57 h). Eight cases received phenobarbital orally on a general ward and 5 intravenously in intensive care units. An improvement in GHB withdrawal symptoms was observed after phenobarbital in all cases and there were no adverse events related to phenobarbital. DISCUSSION AND CONCLUSION: This case series suggests that phenobarbital for the management of benzodiazepine-resistant GHB withdrawal can be safe, even in general inpatient settings, and may avert the progression of delirium. Most data on the management of GHB withdrawal comes from case reports or series, such as this one. This highlights the need for prospective trials to establish an evidence base for therapeutic approaches, including validated measures of withdrawal severity and more information relating to the safe and effective dosing of phenobarbital.
Asunto(s)
Delirio , Oxibato de Sodio , Síndrome de Abstinencia a Sustancias , Humanos , Oxibato de Sodio/uso terapéutico , Estudios Prospectivos , Fenobarbital/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Benzodiazepinas/uso terapéutico , Delirio/inducido químicamente , Delirio/tratamiento farmacológicoRESUMEN
Background: Ingestion of methanol can result in severe irreversible morbidity, and death. Simple and easy methods to detect methanol and other hazardous additives prior to consumption can prevent fatalities. This form of harm reduction is analogous to the widely practiced "pill testing" of recreational drugs in various countries. We aimed to evaluate the performance of two qualitative and quantitative kits to simultaneously identify the presence of methanol and formaldehyde in alcoholic beverages, and compare this to the standard gas chromatographic (GC) method. Methods: Two-hundred samples of Indian and Iranian alcoholic drinks were examined by two new qualitative and quantitative chemical kits designed based on a modified chromotropic acid (CA) method, as well as a gold standard GC method. Results: Methanol levels were similar when evaluated by GC and quantitative method (Z = - 0.328, p = 0.743). The 75th percentile of methanol level detection was 4,290 mg L-1 (range; 0-83,132) using GC compared to that of 4,671 mg L-1 (range; 0-84,960) using the qualitative kit (predefined color intensity reflecting the methanol/ethanol ratio). The quantitative kit was able to detect all methanol-contaminated and non-contaminated samples (110 and 60 cases, respectively: 100% sensitivity). In 25 samples, GC analysis showed no methanol; but the qualitative kit detected possible toxic substances. Formaldehyde measurement by UV/Vis analysis showed the presence of formaldehyde in 23 samples (92%) with a median 912 [IQR 249, 2,109; range 112-2,742] mg L-1. Conclusion: Methanol and formaldehyde can be easily detected using these simple CA chemical kits. Qualitative positive results may indicate the risk of poisoning if the beverage is consumed. CA kits can be used in community setting by public health units and community organizations to monitor for methanol contamination and inform a public health response to reduce methanol-related harms to the public.
Asunto(s)
Bebidas Alcohólicas , Reducción del Daño , Irán , Bebidas Alcohólicas/análisis , Metanol/análisis , Formaldehído/análisisRESUMEN
BACKGROUND: The COVID-19 outbreak was declared a pandemic in March 2020, forcing the United Kingdom into a national lockdown. The aim was to evaluate the effect of this lockdown on hand injuries referred through the trauma and orthopedics virtual fracture clinic (VFC) service and their subsequent management given limited resources. This study also aimed to identify complications and evaluate functional outcomes. METHODS: Patients referred through VFC at Queen Alexandra Hospital during April and May 2020 with hand injuries were analyzed. Isolated injuries to the carpus and wrist were excluded. Controls were compared over identical time spans prior to lockdown and after the restrictions were eased. Functional outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, at 12 months after injury. RESULTS: There was a 68% reduction in referrals of hand injuries during lockdown. Lower numbers of sporting injuries were seen, in contrast to an increased rate of falls, crush injuries, and recreational cycling. Despite a higher number of patients being discharged from VFC during lockdown, there were no increased rates of complications from conservatively managed hand fractures. Eighty percent reported low QuickDASH scores with a median of 2.3. Satisfaction was high, with 73% either satisfied or very satisfied with their treatment and outcome. CONCLUSION: This study demonstrates that there remains a burden of hand trauma during lockdowns, and therefore, service provision for future lockdowns should consider this. Most patients can be managed conservatively, and a high proportion can be discharged from VFC with low complication rates and high satisfaction.