Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value.
Context: Hemoperfusion (HP) or dialysis is occasionally used following carbamazepine (CBZ) toxicity but it remains unclear which is the most efficient modality. We describe a case of severe CBZ intoxication treated with different extracorporeal modalities during which CBZ toxicokinetics were compared. Case details: A 58-year-old man was transferred to our facility 24 hours after ingesting over 14 g of sustained-release CBZ. Because of worsening neurological condition requiring mechanical ventilation and CBZ levels reaching 47.6 µg/mL, he underwent three intermittent hemodialysis (IHD), two continuous veno-venous hemofiltration (CVVH), and one IHD with HP (IHD-HP). IHD and CVVH removed 1.73 g of carbamazepine over 43 hours. Mean apparent half-life was 8.8 hours during IHD 49.1 hours during CVVH, and 5.1 hours during IHD-HP, while measured endogenous half-life after extracorporeal therapies was 81.4 hours. Mean CBZ clearances were 106.2 mL/min during IHD and 21.2 mL/ min during CVVH. His neurological status improved during extracorporeal elimination, and he was discharged without sequela after 16 days. Treatments were well tolerated aside from thrombocytopenia during IHDHP. Discussion: All extracorporeal treatments facilitated CBZ elimination, although CVVH was significantly less efficient than IHD and IHD-HP. IHD-HP may be better than IHD alone but must be weighed against its risks. IHD appears sufficient to eliminate CBZ and may need to be repeated or prolonged according to the clinical context if CBZ absorption is delayed.
A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.
A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments (ECTRs) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.
Hemoperfusion is an extracorporeal treatment based on adsorption, historically reserved for the treatment of acute poisonings. Its use was popularized in the 1970s after several in vitro and animal experiments had demonstrated its efficacy, and was even preferred over hemodialysis in the management of overdosed patients. With the advent of new and more efficient dialytic modalities, hemoperfusion is now less frequently performed in the Western world. However, hemoperfusion still remains popular in developing countries. The present article reviews the technique of hemoperfusion, the factors influencing poison clearance through adsorption and its current applications.
There are currently limited data on the trends in case reporting of poisoned patients undergoing enhanced elimination with an extracorporeal treatment (ECTR). The present manuscript specifically reviews the longitudinal trends of reports according to technique, poison, and country of publication. To identify case reports of ECTR use in the management of poisoning, multiple databases were searched. There were no limitations on language and year of publication. All case reports describing individual patients undergoing ECTR with the intent of enhancing the elimination of a poison were included in the analysis. Since 1913, 2908 reports were identified. There were an increasing number of published reports with time except for a slight decrease during the 1990s. Hemodialysis was by far the most commonly used ECTR in poisoning, followed by hemoperfusion. The number of reported peritoneal dialyses decreased steadily since 1980s. Methanol, ethylene glycol, lithium, and salicylates remained among the most commonly reported poisons in every decade. The large majority of publications originated from either Europe or North America, and more specifically from the United States, Germany, the United Kingdom, and China. Despite the emerging apparition of new techniques, hemodialysis remains to this day the favoured ECTR in the treatment of poisoned patients.
Dialysis-dependent patients are particularly susceptible to the toxic effects of aluminum (Al) because of their impaired ability to eliminate it. Al contamination of dialysis fluid remains a threat in this population. The mechanism for Al diffusion across dialysis membranes is not well established. Our objective is to verify, in AL-exposed patients, the postulate that the direction of Al transfer is predicted by the concentration gradient between free diffusible plasma Al and dialysate Al.
Morbidity and mortality from toxic alcohols like ethylene glycol and methanol remain prevalent worldwide. The introduction of fomepizole, a potent blocker of alcohol dehydrogenase, has modified current practice over the last 15 years. The aim of the study was to describe the characteristics of toxic alcohol poisoning reported to US poison centers, the trends in the incidence of antidote use and hemodialysis treatment, as well as the related mortality. A retrospective study of all electronic entries from the AAPCC National Poison Data System database, from the years 2000 to 2013 was reviewed. When considering all exposures, the great majority of patients had a benign outcome. Major effects (e.g., life threatening) occurred in 2.1% and 4.9% of methanol and ethylene glycol cases, respectively. Mortality rates were similar for both toxic alcohols, approximately 0.6%. When only considering ingestions reported to healthcare facilities, a major effect was reported in 9.5% and 20.5%, and the mortality rate was 2.9% and 2.4% for methanol and ethylene glycol exposures, respectively, and remained constant over time. The use of fomepizole increased statistically over the study period while that of ethanol decreased, until it became proportionally negligible by 2012-2013. The use of hemodialysis significantly decreased in "Early" ethylene glycol exposures during the study period. Similar to other reports, it appears that the use of fomepizole has largely supplanted ethanol as the antidote of choice in toxic alcohol exposures and may decrease the requirements for hemodialysis in patients poisoned with ethylene glycol who have no acidosis and normal kidney function.
The Extracorporeal Treatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, the workgroup presents its results for tricyclic antidepressants (TCAs). After an extensive literature search, using a predefined methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed in person at a meeting. A second vote determined the final recommendations. Seventy-seven articles met inclusion criteria. Only case reports, case series, and one poor-quality observational study were identified yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers that poisoned patients with TCAs are not likely to have a clinical benefit from extracorporeal removal and recommends it NOT to be used in TCA poisoning.
Poisoning is a significant public health problem. In severe cases, extracorporeal treatments (ECTRs) may be required to prevent or reverse major toxicity. Available ECTRs include intermittent hemodialysis, sustained low-efficiency dialysis, intermittent hemofiltration and hemodiafiltration, continuous renal replacement therapy, hemoperfusion, therapeutic plasma exchange, exchange transfusion, peritoneal dialysis, albumin dialysis, cerebrospinal fluid exchange, and extracorporeal life support. The aim of this article was to provide an overview of the technical aspects, as well as the potential indications and limitations of the different ECTRs used for poisoned patients.
The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life-saving in a limited number of scenarios. The decision-processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poison's physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.
The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR is indicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present.
Nephrologists and critical care physicians are commonly involved in the treatment of severely poisoned patients. Various techniques exist presently to enhance the elimination of poisons. Corporeal treatments occur inside of the body and include multiple-dose activated charcoal, resin binding, forced diuresis, and urinary pH alteration. Extracorporeal treatments include hemodialysis, hemoperfusion, peritoneal dialysis, continuous renal replacement therapy, exchange transfusion, and plasmapheresis. This review illustrates the potential indications and limitations in the application of these modalities as well as the pharmacological characteristics of poisons amenable to enhanced elimination.
Current practice guidelines recommend that pulmonary blastomycosis be treated with antifungal agents such as amphotericin B and itraconazole. Echinocandins are not recommended because of poor in vitro activity against Blastomyces dermatitidis and lack of supporting clinical data. We report a case of chronic pulmonary blastomycosis treated successfully with caspofungin.
Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition.
Contrary to popular opinion, application of extracorporeal therapies for poisonings predates their use for ESRD. Despite this observation, the science of blood purification in toxicology remains desperately stagnant today. In fact, much of our current knowledge is derived from George Schreiners 1958 review. Original publications are almost exclusively composed of case reports and case series, from which good inference is impossible. Until randomized controlled trials become available, the medical community would be well served by a group mandated to systematically review available literature, extract relevant information, provide recommendations based on current evidence, and propose research initiatives. The EXtracorporeal TReatments In Poisoning workgroup, formed by several international experts in different medical fields and represented by over 20 societies, now has this mission.
Vascular access-related bloodstream infection (BSI) is frequent among patients undergoing hemodialysis increasing their morbidity and mortality, but its occurrence across various dialysis centre types is not known. The aims of this study were to describe the incidence rates and assess the variability in BSI risk between dialysis centre types and other centre-level variables.
Treatment of Clostridium difficile infection (CDI) is often limited by recurrence in 25% of cases. The objective of this study was to determine risk factors of CDI recurrence during a provincial endemic.
The Del Pozo and Patel (DPP) algorithm permits to identify suitable candidates for debridement and implant retention (DR) in prosthetic joint infections (PJI), but does not include gram-negative bacilli (GNB) as a risk factor of worst outcome. We conducted a retrospective study to validate the DPP algorithm and propose a simplified algorithm including GNB PJI. From 2002 to 2009, 73 PJI underwent surgery; 55% were chosen according to PDD algorithm. Non-adherence increased the risk of treatment failure (HR = 4.2). Performing DR in the presence of GNB PJI and performing DR in a joint prosthesis implanted for >3 months without hematogenous infection were independent risk factors. Our simplified algorithm, based on these 2 criteria, showed comparable performance to the DPP algorithm but increased eligibility for DR by a 2.4 fold.
Widespread Al toxicity is unusual today. In 2005, Canadian peritoneal dialysis (PD) centers reported widespread hyperaluminemia in patients using dialysates from one specific manufacturer. Our objectives were to evaluate risk factors related to Al accumulation and to assess its clinical consequences in patients from 2 centers.
The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl).
Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.
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