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  1. Article ; Online: Management of Poisonings and Intoxications.

    Ghannoum, Marc / Roberts, Darren M

    Clinical journal of the American Society of Nephrology : CJASN

    2023  Volume 18, Issue 9, Page(s) 1210–1221

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Antidotes/therapeutic use ; Charcoal/therapeutic use ; Acetylcysteine/therapeutic use ; Ethanol ; Poisons ; Poisoning/diagnosis ; Poisoning/therapy
    Chemical Substances Antidotes ; Charcoal (16291-96-6) ; Acetylcysteine (WYQ7N0BPYC) ; Ethanol (3K9958V90M) ; Poisons
    Language English
    Publishing date 2023-01-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.0000000000000057
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Expanding the evidence for managing metformin poisoning to support decision-making.

    Roberts, Darren M / Ghannoum, Marc

    Clinical toxicology (Philadelphia, Pa.)

    2022  Volume 61, Issue 4, Page(s) 203–206

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Retrospective Studies ; Acidosis, Lactic ; Metformin ; Drug Overdose/therapy ; Acidosis ; Renal Dialysis ; Poisoning/therapy ; Hypoglycemic Agents
    Chemical Substances Metformin (9100L32L2N) ; Hypoglycemic Agents
    Language English
    Publishing date 2022-08-05
    Publishing country England
    Document type Systematic Review ; Journal Article
    ZDB-ID 204476-6
    ISSN 1556-9519 ; 0009-9309 ; 0731-3810 ; 1556-3650
    ISSN (online) 1556-9519
    ISSN 0009-9309 ; 0731-3810 ; 1556-3650
    DOI 10.1080/15563650.2023.2196372
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Letter to the editor concerning the case report "Successful treatment of severe quetiapine intoxication with CytoSorb hemoadsorption".

    Kielstein, Jan T / Schmidt, Julius J / Ghannoum, Marc

    Journal of clinical pharmacy and therapeutics

    2022  Volume 47, Issue 9, Page(s) 1493–1494

    MeSH term(s) Cytokines ; Humans ; Quetiapine Fumarate ; Shock, Septic
    Chemical Substances Cytokines ; Quetiapine Fumarate (2S3PL1B6UJ)
    Language English
    Publishing date 2022-08-02
    Publishing country England
    Document type Case Reports ; Letter ; Comment
    ZDB-ID 639006-7
    ISSN 1365-2710 ; 0269-4727
    ISSN (online) 1365-2710
    ISSN 0269-4727
    DOI 10.1111/jcpt.13749
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effectiveness of CytoSorb in cases of acute amitriptyline intoxication is not proven.

    Kielstein, Jan T / Schmidt, Julius J / Ghannoum, Marc

    Journal of clinical pharmacy and therapeutics

    2021  Volume 47, Issue 3, Page(s) 420

    MeSH term(s) Amitriptyline ; Antidepressive Agents, Tricyclic ; Humans
    Chemical Substances Antidepressive Agents, Tricyclic ; Amitriptyline (1806D8D52K)
    Language English
    Publishing date 2021-07-07
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 639006-7
    ISSN 1365-2710 ; 0269-4727
    ISSN (online) 1365-2710
    ISSN 0269-4727
    DOI 10.1111/jcpt.13483
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hemodialysis for lamotrigine poisoning.

    Gosselin, Sophie / Ghannoum, Marc / Hoffman, Robert S

    The American journal of emergency medicine

    2019  Volume 38, Issue 2, Page(s) 403–404

    MeSH term(s) Drug Overdose ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Lamotrigine ; Renal Dialysis
    Chemical Substances Lamotrigine (U3H27498KS)
    Language English
    Publishing date 2019-08-04
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 605890-5
    ISSN 1532-8171 ; 0735-6757
    ISSN (online) 1532-8171
    ISSN 0735-6757
    DOI 10.1016/j.ajem.2019.158385
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The serum glycolate concentration: its prognostic value and its correlation to surrogate markers in ethylene glycol exposures.

    Roberts, Darren M / Hoffman, Robert S / Brent, Jeffrey / Lavergne, Valéry / Hovda, Knut Erik / Porter, William H / McMartin, Kenneth E / Ghannoum, Marc

    Clinical toxicology (Philadelphia, Pa.)

    2022  Volume 60, Issue 7, Page(s) 798–807

    Abstract: Context: 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 ...

    Abstract Context: 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.
    Objectives: 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 (
    Methods: 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.
    Results: 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 (
    Conclusions: This systematic review demonstrates that the glycolate concentration predicts mortality (unlikely if <8 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.
    MeSH term(s) Acute Kidney Injury/chemically induced ; Acute Kidney Injury/diagnosis ; Bicarbonates ; Biomarkers ; Ethylene Glycol ; Glycolates ; Humans ; Prognosis ; Retrospective Studies
    Chemical Substances Bicarbonates ; Biomarkers ; Glycolates ; Ethylene Glycol (FC72KVT52F)
    Language English
    Publishing date 2022-03-24
    Publishing country England
    Document type Journal Article ; Systematic Review
    ZDB-ID 204476-6
    ISSN 1556-9519 ; 0009-9309 ; 0731-3810 ; 1556-3650
    ISSN (online) 1556-9519
    ISSN 0009-9309 ; 0731-3810 ; 1556-3650
    DOI 10.1080/15563650.2022.2049811
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: What is the role of renal replacement therapy in the setting of dabigatran toxicity?

    Ghannoum, Marc / Nolin, Thomas D

    Seminars in dialysis

    2014  Volume 27, Issue 3, Page(s) 223–226

    MeSH term(s) Antithrombins/adverse effects ; Antithrombins/therapeutic use ; Benzimidazoles/adverse effects ; Benzimidazoles/therapeutic use ; Dabigatran ; Global Health ; Hemorrhage/chemically induced ; Hemorrhage/epidemiology ; Humans ; Incidence ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/therapy ; Renal Replacement Therapy/methods ; Thromboembolism/complications ; Thromboembolism/drug therapy ; beta-Alanine/adverse effects ; beta-Alanine/analogs & derivatives ; beta-Alanine/therapeutic use
    Chemical Substances Antithrombins ; Benzimidazoles ; beta-Alanine (11P2JDE17B) ; Dabigatran (I0VM4M70GC)
    Language English
    Publishing date 2014-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1028193-9
    ISSN 1525-139X ; 0894-0959
    ISSN (online) 1525-139X
    ISSN 0894-0959
    DOI 10.1111/sdi.12230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Hemodialysis removal of caffeine.

    Ghannoum, Marc / Hoffman, Robert S / Roberts, Darren M / Lavergne, Valery / Nolin, Thomas D / Gosselin, Sophie

    The American journal of emergency medicine

    2020  Volume 38, Issue 6, Page(s) 1273–1274

    MeSH term(s) Caffeine ; Drug Overdose ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Renal Dialysis
    Chemical Substances Caffeine (3G6A5W338E)
    Language English
    Publishing date 2020-02-19
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 605890-5
    ISSN 1532-8171 ; 0735-6757
    ISSN (online) 1532-8171
    ISSN 0735-6757
    DOI 10.1016/j.ajem.2020.02.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup.

    Ghannoum, Marc / Gosselin, Sophie / Hoffman, Robert S / Lavergne, Valery / Mégarbane, Bruno / Hassanian-Moghaddam, Hossein / Rif, Maria / Kallab, Siba / Bird, Steven / Wood, David M / Roberts, Darren M

    Critical care (London, England)

    2023  Volume 27, Issue 1, Page(s) 56

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Antidotes/therapeutic use ; Fomepizole ; Ethanol ; Renal Dialysis/methods ; Glycolates ; Ethylene Glycol ; Poisoning/therapy
    Chemical Substances Antidotes ; Fomepizole (83LCM6L2BY) ; Ethanol (3K9958V90M) ; glycolic acid (0WT12SX38S) ; Glycolates ; Ethylene Glycol (FC72KVT52F)
    Language English
    Publishing date 2023-02-10
    Publishing country England
    Document type Systematic Review ; Journal Article
    ZDB-ID 2041406-7
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-022-04227-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup.

    Bouchard, Josée / Shepherd, Greene / Hoffman, Robert S / Gosselin, Sophie / Roberts, Darren M / Li, Yi / Nolin, Thomas D / Lavergne, Valéry / Ghannoum, Marc

    Critical care (London, England)

    2021  Volume 25, Issue 1, Page(s) 201

    Abstract: Background: β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to ... ...

    Abstract Background: β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
    Methods: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
    Results: A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
    Conclusions: BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
    MeSH term(s) Adrenergic beta-Antagonists/pharmacokinetics ; Adrenergic beta-Antagonists/pharmacology ; Adrenergic beta-Antagonists/poisoning ; Consensus ; Drug Overdose/etiology ; Drug Overdose/therapy ; Extracorporeal Membrane Oxygenation/methods ; Extracorporeal Membrane Oxygenation/statistics & numerical data ; Humans
    Chemical Substances Adrenergic beta-Antagonists
    Language English
    Publishing date 2021-06-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
    ZDB-ID 2041406-7
    ISSN 1466-609X ; 1364-8535
    ISSN (online) 1466-609X
    ISSN 1364-8535
    DOI 10.1186/s13054-021-03585-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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