Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

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.

High-efficiency, high-flux in-line hemofiltration using a high blood flow extracorporeal circuit.

The ability of current renal replacement therapy modalities to achieve rapid solute removal is limited by membrane surface area and blood flow rate. Extracorporeal membrane oxygenation offers high blood flow and hemodynamic support that may be harnessed to overcome limitations in traditional renal replacement therapy. Using an extracorporeal membrane oxygenation circuit, we describe a high blood flow, high-efficiency hemofiltration technique using in-line hemofilters (hemoconcentrators) and standard replacement fluid to enhance solute clearance. Using this approach and a total of 5 L of replacement volume per treatment, creatinine (Cr) clearances of 8.3 L/hour and 11.2 L/hour using one and two hemoconcentrators, respectively, were achieved. With use of a high blood flow rate of up to 5 L/min, this hemofiltration technique can potentially offer clearance of 30 times that of continuous renal replacement therapy and of 6 times that of hemodialysis which may expand the ability to remove substances traditionally not considered removable via existing extracorporeal therapies.

A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut (0) methylmalonic acidemia.

End stage kidney disease is a well-known complication of methylmalonic acidemia (MMA), and can be treated by dialysis, kidney transplant, or combined kidney-liver transplant. While liver and/or kidney transplantation in MMA may reduce the risk of metabolic crisis and end-organ disease, it does not fully prevent disease-related complications. We performed detailed metabolite and kinetic analyses in a 28-year-old patient with mut (0) MMA who underwent hemodialysis for 6 months prior to receiving a combined liver/kidney transplant. A single hemodialysis session led to a 54 % reduction in plasma methylmalonic acid and yielded a plasma clearance of 103 ml/min and VD0.48 L/kg, which approximates the total body free water space. This was followed by rapid reaccumulation of methylmalonic acid over 24 h to the predialysis concentration in the plasma. Following combined liver/kidney transplantation, the plasma methylmalonic acid was reduced to 3 % of pre-dialysis levels (6,965 ± 1,638 (SD) µmol/L and 234 ± 100 (SD) µmol/L) but remained >850× higher than the upper limit of normal (0.27 ± 0.08 (SD) µmol/L). Despite substantial post-operative metabolic improvement, the patient developed significant neurologic complications including acute worsening of vision in the setting of pre-existing bilateral optic neuropathy, generalized seizures, and a transient, focal leukoencephalopathy. Plasma methylmalonic acid was stable throughout the post-operative course. The biochemical parameters exhibited by this patient further define the whole body metabolism of methylmalonic acid in the setting of dialysis and subsequent combined liver/kidney transplant.

Toxin-Induced Liver Injury and Extracorporeal Treatment of Liver Failure.

Poisoning with a large variety of drugs and naturally occurring toxins may result in acute liver injury and failure. Drug-induced liver injury is a major cause of liver failure nationwide, and it is likely that nephrologists will be involved in treating patients with these conditions. A number of xenobiotics resulting in liver toxicity may cause acute kidney injury or other organ injury as well. Most agents causing drug- or toxin-induced liver failure lack specific therapies, although a few xenobiotics such as acetaminophen have effective antidotal therapies if administered prior to development of hepatotoxicity. The nephrologist should be aware that extracorporeal treatment of liver failure associated with drugs and toxins may be indicated, including therapies conventionally performed by nephrologists (hemodialysis, continuous kidney replacement therapy), therapies occasionally performed by nephrologists and other specialists (plasma exchange, albumin dialysis, hemadsorption), and therapies performed by other specialists (extracorporeal membrane oxygenation). An overview of the role of these therapies in liver failure is provided, as well as a review of their limitations and potential complications.

The Impact of Non-opioid Analgesic Usage on Total Opioid Load During Traumatic Brain Injury Rehabilitation: A Retrospective Study.

Background Patients staying in acute rehabilitation often use large amounts of opioids during their stay. There are a number of reasons for this increased opioid exposure, including but not limited to daily exercises with physical and occupational therapists, increased demand on a healing body, and use of previously atrophying musculature. Some physiatrists have noticed that patients who concurrently are prescribed medications such as Robaxin seem to require fewer opioids during their stay in acute rehabilitation. This study aimed to determine the association between non-opioid analgesic use and total opioid load, as measured using morphine milligram equivalents (MMEs), during inpatient rehabilitation for traumatic brain injury. Methodology A retrospective study of individuals with a diagnosis of traumatic brain injury admitted to an acute inpatient rehabilitation program was performed. Non-opioid medications that were reviewed in the study included acetaminophen, amitriptyline, baclofen, diclofenac, gabapentin, ibuprofen, lidocaine, methocarbamol, nortriptyline, and pregabalin. Five of the most-used non-opioid medications (acetaminophen, diclofenac, gabapentin, lidocaine, and methocarbamol) were statistically analyzed using regression and analysis of variance to evaluate for any significant variables. Results Results showed that the average daily dose of acetaminophen has a significant effect on the average daily MME and that the average daily dose of gabapentin and methocarbamol each have a significant effect on the change of daily MME usage from admission to discharge from acute rehab (ΔMME). Results also showed that the mere presence of methocarbamol (regardless of daily or total dosage) had a significant effect on the ΔMME. Conclusions Based on these findings, physicians may want to consider prescribing acetaminophen, gabapentin, or methocarbamol for patients admitted for inpatient rehabilitation following traumatic brain injury who require high amounts of opioids.

Adapting an Objective Structured Clinical Examination (OSCE) on Conducting Difficult Conversations Between Nephrology Fellows and Patients to a Virtual Platform: A Research Letter.

Background: We previously described a nephrology-specific "Breaking Bad News" Objective Structured Clinical Examination (OSCE) assessing nephrology fellow communication and counseling skills in 3 scenarios: kidney replacement therapy (KRT) in kidney failure, urgent KRT in acute kidney injury (AKI), and kidney biopsy (KBx). Objective: The main objectives of this study is to adapt the OSCE to a virtual platform, simulating nephrology patient telemedicine encounters involving difficult conversations, and to assess fellow and faculty satisfaction with the virtual format. Design: Description of a formative telemedicine simulation for nephrology fellows. Setting: Fully virtual simulation conducted by 2 academic medical simulation centers. Participants: Nephrology faculty and fellows at 3 urban/suburban training programs in the eastern United States. Measurements: Description of the virtual OSCE process. Fellow and faculty satisfaction overall and for each scenario. Faculty and fellow estimates of frequency of virtual patient encounters in the past year. Methods: The OSCE consisted of 3 scenarios: KRT in kidney failure, urgent KRT in AKI, and KBx. Objective Structured Clinical Examinations were administered in May 2021. Each scenario lasted 20 minutes. The AKI scenario was audio only. Fellows telephoned a simulated patient surrogate for urgent KRT consent. Kidney failure and KBx scenarios were video encounters. Faculty observed while muted/video off. Immediately after the OSCE, fellows and faculty were anonymously surveyed regarding their satisfaction with each scenario, the OSCE overall, and their estimate of outpatient encounters and inpatient KRT counseling done virtually in the preceding year. Results: Seventeen fellows completed the OSCE at 2 centers (3 programs). Sixteen (94%) completed the survey. Almost 94% rated the OSCE as a good/very good approximation of telemedicine encounters. Those satisfied/very satisfied with each scenario are as follow: 100% for AKI, 75% for kidney failure, and 75% for KBx. Two commented that they often did urgent KRT counseling by telephone. Fellows estimated a median 20% (interquartile range: 175, 50%) of counseling for acute inpatient KRT and a median 50% (IQR: 33.75, 70%) of outpatient encounters were virtual in the prior year. Two (regarding the kidney failure and KBx scenarios) indicated they would not have counseled similar outpatients virtually. Limitations: The 15-minute interactions may be too short to allow the encounter to be completed comfortably. A small number of programs and fellows participated, and programs were located in urban/suburban areas on the east coast of the United States. Conclusions: Overall, fellows felt that the OSCE was a good approximation of virtual encounters. The OSCE is an opportunity for fellows to practice telemedicine communication skills.

Contexte: Nous avions précédemment décrit un examen clinique objectif structuré (ECOS) de type « annonce d'une mauvaise nouvelle ¼ en néphrologie afin d'évaluer les compétences en communication et consultation des résidents en néphrologie. L'ECOS comportait trois scénarios: thérapie de remplacement rénal (TRR) pour l'insuffisance rénale, TRR urgente dans les cas d'insuffisance rénale aiguë (IRA), et biopsie du rein (BxR). Objectifs: Adapter l'ECOS à une plateforme virtuelle, simuler des rencontres de télémédecine impliquant des conversations difficiles avec des patients en néphrologie, et évaluer la satisfaction des résidents en néphrologie et du corps enseignant à l'égard du format virtuel. Conception: Description d'une simulation de télémédecine pour la formation des résidents en néphrologie. Cadre: Des simulations entièrement virtuelles réalisées dans deux centers universitaires de simulation médicale. Participants: Les professeurs et les résidents en néphrologie de trois programs de formation urbains/suburbains de l'est des États-Unis. Mesures: Description du processus de l'ECOS virtuel. Satisfaction générale des résidents en néphrologie et du corps enseignant pour chacun des scénarios. Estimation, par les professeurs et les résidents, de la fréquence des rencontres virtuelles avec des patients au cours de la dernière année. Méthodologie: L'ECOS était composé de trois scénarios: TRR en insuffisance rénale; TRR urgente en contexte d'IRA et biopsie rénale. Les ECOS ont été réalisés en mai 2021. Chaque scénario durait 20 minutes. Le scénario IRA était audio uniquement; les boursiers devaient téléphoner à un patient simulé afin d'obtenir un consentement pour une TRR urgente. Les scénarios pour l'insuffisance rénale terminale et la BxR étaient sous forme de rencontres vidéo. Les professeurs observaient les scénarios en sourdine/hors vidéo. Immédiatement après l'ECOS, les résidents en néphrologie et les professeurs ont été interrogés de façon anonyme sur leur satisfaction à l'égard de chaque scénario et de l'ECOS dans son ensemble. Ils ont également été invités à estimer le nombre de consultations externes et de conseils prodigués sur la TRR à des patients hospitalisés au cours de l'année précédente. Résultats: Dix-sept résidents en néphrologie ont complété l'ECOS dans les deux centers (trois programs) et seize (94 %) ont répondu au sondage. La très grande majorité (94 %) a évalué l'ECOS comme une bonne/très bonne simulation des rencontres de télémédecine. Le taux de personnes satisfaites/très satisfaites s'établissait à 100 % pour le scénario de l'IRA, à 75 % pour celui de l'insuffisance rénale terminale et à 75 % pour celui de la BxR. Deux personnes ont dit faire régulièrement des consultations par téléphone pour la TRR urgente. Les résidents en néphrologie ont estimé que 20 %, (proportion médiane) ÉIQ= 175; 50 %, des consultations avec des patients hospitalisés et 50 %, (proportion médiane) ÉIQ = 33,75; 70 %, des consultations externes avaient été faites virtuellement au cours de l'année précédente. Pour les scénarios d'insuffisance rénale terminale et de BxR, deux personnes ont indiqué qu'elles ne feraient pas de consultations virtuelles pour ces patients. Limites: Les interactions de 15 minutes sont probablement trop courtes pour compléter confortablement la rencontre. Un faible nombre de programs et de résidents en néphrologie ont participé. Les programs évalués se situaient en zones urbaines et suburbaines de la côte est des États-Unis. Conclusion: Dans l'ensemble, les résidents en néphrologie ont estimé que l'ECOS était une bonne représentation des rencontres virtuelles. L'ECOS est une occasion pour les résidents de mettre en pratique leurs compétences en communication dans un contexte de télémédecine.

Mass Poisoning From Ethylene Glycol at a U.S. Military Base.

Ethylene glycol (EG) toxicity is an important cause of toxic alcohol poisoning in the USA with over 5,000 exposures reported annually. While classically characterized by solitary accidental or intentional ingestions, mass toxic alcohol poisoning outbreaks and more rarely collective consumptions (typically of methanol) have been described. We describe an ethylene glycol poisoning from collective ingestion that involved soldiers presenting at William Beaumont Army Medical Center in El Paso, Texas. Eleven soldiers presented to the emergency department over a 12-h period after ingestion of an unknown substance. The first two patients exhibited severe neurologic symptoms, while the remainder were asymptomatic. As serum EG levels were not immediately available, treatment decisions were based on surrogate laboratory values. Two patients received immediate hemodialysis, and fomepizole (FOM) because of severe acidosis with elevated anion and osmolal gaps. These patients developed acute kidney injury with renal recovery within a 3-week period. Two patients with elevated lactate received bicarbonate-based intravenous (IV) fluids and FOM. Two patients received IV fluids only and required prolonged observation for worsening acidosis and/or acute kidney injury. Five patients with normal laboratory values were treated with IV fluids and observation. All patients received cofactors including thiamine and pyridoxine. All patients survived. The outbreak occurred in the setting of limited dialysis resources, limited FOM availability, and in a resource-limited community. Additional guidelines are needed to determine allocation of limited resources, optimal dialysis and FOM treatment course, and comorbid conditions, which may prolong recovery.

Toxic Alcohol Poisoning.

This article reviews the background, metabolism, clinical effects, and treatment of toxic alcohols, specifically ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropyl alcohol. This article also reviews the importance of an anion gap metabolic acidosis in relation to toxic alcohols and explores both the utility and the limitations of the osmol gap in patient management.

In vitro analysis of n-acetylcysteine (NAC) interference with the international normalized ratio (INR).

BACKGROUND: Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro. METHODS: Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p = .0008, Stago p < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p = .02 and p = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p < .0001, Stago p < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p < .05). CONCLUSION: Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

Outcomes of acute exploratory pediatric lithium ingestions.

Objectives: To date, very little literature describes the outcomes of acute unintentional ingestions of lithium in young children. This study aimed to describe the clinical effects and outcomes reported in these patients reported to the National Poison Data System (NPDS).Methods: This is a retrospective observational study of acute unintentional lithium ingestions in children <6 years of age. The primary intent of the study was to characterize acute unintentional exposures to lithium in children in this age group. As a secondary outcome, we sought to identify a weight-based threshold to empirically refer patients into a healthcare facility for symptoms consistent with moderate effect or worse. The American Association of Poison Control Centers' NPDS was queried for all acute ingestions of lithium salts in children <6 years of age from 2000 to 2018. Inclusion criteria were single substance ingestions, unintentional-general exposure (i.e., exploratory ingestion), and followed to a known outcome or coded as potentially toxic exposure unable to follow and the patient was experiencing symptoms.Results: A total of 3045 single-substance exploratory ingestions of lithium were reported to poison centers that showed a decrease over time, consistent with decreasing use of lithium and decreasing calls to poison centers. Of the 3045 cases, we excluded 1178 leaving 1863 cases for analysis. Median age was 2 years (IQR: 1.5, 2) with 51% male cases. Management site was primarily non-health care facility (n = 808; 43.4%) with 569 (30.5%) already in a healthcare facility (HCF) when the Poison Control Center (PCC) was called and 477 (25.6%) referred to a HCF. The route of exposure was most commonly ingestion (n = 1853; 99.5%) and site of exposure was primarily home (1743; 93.6%). Medical outcomes were predominantly no effect and minor effect. There were 262 related clinical effects were reported in 184 patients (10%). The most frequently reported were vomiting (n = 76), drowsiness/lethargy (n = 58), other (n = 22), and ataxia (n = 20). Clinical effects lasted ≤2 h for 65 (33%), 2-8 h for 57 (28.9%), 8-24 h for 51 (25.9%), 1-3 days for 11 (5.6%), and >3 days to ≤1 week for 1 (0.5%); no cases resulted in clinical effects thought to be permanent and no deaths were reported. There were 1173 treatments provided to 857 patients. The most common treatments were basic and are readily performed at home; dilution (n = 492) and food/snack (n = 180). A smaller subset of patients received care that could likely only be provided in a healthcare facility including IV fluids (n = 173), other (n = 120), whole bowel irrigation (n = 46), single dose activated charcoal (n = 41), syrup of ipecac (n = 34), and lavage (n = 31). No patients received hemodialysis. A total of 425 of the exposures were referred to a healthcare facility by the PCC which had a dose coded. There was no difference in dose that resulted to referral to a healthcare facility over time (p = 0.2747). Due to the small number of moderate/major effect cases with dose information, we were unable to identify a dose-based threshold for referral to HCF.Conclusions: Severe outcomes after unintentional ingestion of lithium in pediatric patients are rare. It is likely that most asymptomatic pediatric patients <6 years do not need to be referred to the hospital after ingestion of lithium.

Radiocesium in migratory aquatic game birds using contaminated U.S. Department of Energy reactor-cooling reservoirs: A long-term perspective.

Low-level releases of radiocesium into former nuclear reactor cooling-reservoirs on the U.S. Department of Energy's Savannah River Site (SRS) in South Carolina, USA, dating primarily to the late 1950s and early 1960s, have allowed examination of long-term contaminant attenuation in biota occupying these habitats. Periodic collections of migratory game birds since the 1970s have documented 137Cs (radiocesium) activity concentrations in birds of SRS reservoirs, including mainly Par Pond and Pond B. In this study, during 2014 and 2015 we released wild-caught American coots (Fulica americana) and ring-necked ducks (Aythya collaris) onto Pond B. We made lethal collections of these same birds with residence times ranging from 32 to 173 days to examine radiocesium uptake and estimate the rate of natural attenuation. The two species achieved asymptotic whole-body activity concentrations of radiocesium at different times, with ring-necked ducks requiring almost three times longer than the 30-35 days needed by coots. We estimated ecological half-life (Te) for Pond B coots over a 28-yr period as 16.8 yr (95% CI = 12.9-24.2 yr). Pond B coot Te was nearly four times longer than Te for coots at nearby Par Pond where radiocesium bioavailability had been constrained for decades by pumping of potassium-enriched river water into that reservoir. Te could not be estimated from long-term data for radiocesium in Pond B diving ducks, including ring-necked ducks, likely because of high variability in residence times of ducks on Pond B. Our results highlight the importance: (1) for risk managers to understand site-specific bio-geochemistry of radiocesium for successful implementation of countermeasures at contaminated sites and (2) of residence time as a critical determinant of observed radiocesium activity concentrations in highly mobile wildlife inhabiting contaminated habitats.

Abuse, misuse, and suicidal substance use by children on school property.

OBJECTIVE: The purpose of this study was to characterize the epidemiological trends associated with substances used in intentional exposures among children while on school property reported to the U.S. National Poison Data System (NPDS). MATERIALS AND METHODS: NPDS was queried for intentional (abuse, misuse, suspected suicide, and unknown intentional) exposures reported to occur on school property between calendar years 2004 and 2013. Records were restricted to children 6-18 years of age. Demographic, exposure, and clinical characteristics were assessed. RESULTS: A total of 56,882 substances were intentionally used on school property by 50,379 children, of which 39.8% were females (n = 20,070), 57.7% were males (n = 29,084), and 2.4% were unknown gender (n = 1,225). The most frequent pharmaceutical exposures reported included sedatives (n = 4,096; 8.1%), analgesics (n = 4,022; 8.0%), and cough and cold preparations (n = 3,529; 7.0%). The majority of exposures were managed on site (n = 21,464; 42.6%), followed by care at a healthcare facility (n = 20,048; 39.7%). Serious outcomes (moderate or major effects and death) accounted for nine percent of all reported exposures. Compared to reference groups, female gender, teenagers 17-18 years, and pharmaceutical substances (Prevalence Ratios = 4.6, 9.4, and 9.9, respectively) were associated with suspected suicides when compared with other intentional exposures. CONCLUSIONS: Along with other national data about behaviors in the adolescent and teenage population, additional trends in risky behavior may be gleaned by surveillance through poison centers. With over 5,000 annual reports to the poison centers about intentional exposures on school property, school personnel and parents/guardians must be vigilant about the range of pharmaceutical and non-pharmaceutical substances that are used for abuse, misuse, or suicide.

Osmotic demyelination syndrome.

The osmotic demyelination syndrome (ODS) has been a recognized complication of the rapid correction of hyponatremia for decades. However, in recent years, a variety of other medical conditions have been associated with the development of ODS, independent of changes in serum sodium. This finding suggests that the pathogenesis of ODS may be more complex and involve the inability of brain cells to respond to rapid changes in osmolality of the interstitial (extracellular) compartment of the brain, leading to dehydration of energy-depleted cells with subsequent axonal damage that occurs in characteristic areas. Features of the syndrome include quadriparesis and neurocognitive changes in the presence of characteristic lesions found on magnetic resonance imaging of the brain. Although slow correction of hyponatremia seems to be the best way to prevent development of the syndrome, there are new data that suggest reintroduction of hyponatremia in those patients who have undergone inadvertent rapid correction of the serum sodium and corticosteroids may play a role in prevention of ODS.