CJASN ePress. Published on August 22, 2019 as doi: 10.2215/CJN.

02560319

Extracorporeal Removal of Poisons and Toxins

Joshua David King,1,2 Moritz H. Kern,3,4 and Bernard G. Jaar 5,6,7,8

Abstract
Extracorporeal therapies have been used to remove toxins from the body for over 50 years and have a greater role
than ever before in the treatment of poisonings. Improvements in technology have resulted in increased efficacy of
removing drugs and other toxins with hemodialysis, and newer extracorporeal therapy modalities have expanded
the role of extracorporeal supportive care of poisoned patients. However, despite these changes, for at least the 1
Division of
past three decades the most frequently dialyzed poisons remain salicylates, toxic alcohols, and lithium; in addition, Nephrology,
the extracorporeal treatment of choice for therapeutic removal of nearly all poisonings remains intermittent University of
Maryland, Baltimore,
hemodialysis. For the clinician, consideration of extracorporeal therapy in the treatment of a poisoning depends
Maryland; 2Maryland
upon the characteristics of toxins amenable to extracorporeal removal (e.g., molecular mass, volume of Poison Center,
distribution, protein binding), choice of extracorporeal treatment modality for a given poisoning, and when the Baltimore, Maryland;
3
benefit of the procedure justifies additive risk. Given the relative rarity of poisonings treated with extracorporeal Department of
therapies, the level of evidence for extracorporeal treatment of poisoning is not robust; however, extracorporeal Medicine, University
Hospital Heidelberg,
treatment of a number of individual toxins have been systematically reviewed within the current decade by the University of
Extracorporeal Treatment in Poisoning workgroup, which has published treatment recommendations with an Heidelberg,
improved evidence base. Some of these recommendations are discussed, as well as management of a small Heidelberg, Germany;
4
number of relevant poisonings where extracorporeal therapy use may be considered. DZHK (German
Centre for
CJASN 14: ccc–ccc, 2019. doi: https://doi.org/10.2215/CJN.02560319 Cardiovascular
Research), Partner Site
Heidelberg/
Introduction is determined primarily by the lipophilicity of a sub- Mannheim,
Since 1914, when the first in vivo hemodialysis (HD) Mannheim, Germany;
stance; nonpolar, lipophilic toxins have high volumes 5
Department of
was performed, extracorporeal therapies have been of distribution and are not generally dialyzable, Medicine, Johns
used for the removal of drugs and other toxins (1). whereas hydrophilic toxins have lower volumes of Hopkins School of
Over the past 50 years, there has been increasing use of distribution and are more easily dialyzable. Solutes Medicine, Baltimore,
extracorporeal therapies for the treatment of poisoning, with volumes of distribution .1–1.5 L/kg are poorly Maryland; 6Welch
Center for Prevention,
both for removal of toxins and supportive therapy; this amenable to extracorporeal removal (see Table 2) (5,6). Epidemiology and
review focuses primarily upon the former (2). Although In plasma, almost all solutes are protein-bound to Clinical Research,
the increasing importance of extracorporeal therapies some degree (5). The plasma proteins that bind drugs Johns Hopkins
in managing poisons is likely due in part to the greater are too large to be removed via extracorporeal ther- University, Baltimore,
number of available modalities, intermittent HD has Maryland;
apies other than apheresis, and the fraction of toxins 7
Department of
become more efficacious at removing toxins over time that are protein-bound are not removed via HD (6,7). Epidemiology, Johns
as technology has progressed, and it is likely that Substances with ,80% protein binding are typically Hopkins Bloomberg
the role of extracorporeal therapies for poisoning amenable to extracorporeal removal via HD (6,8). The School of Public
will continue to grow and evolve over time (3,4). logarithmic nature of extracorporeal solute removal Health, Baltimore,
Maryland; and
(Figure 1) results in little difference between the 8
Nephrology Center of
removal of a substance that is, for example, 20% Maryland, Baltimore,
Principles of Toxin Removal by Extracorporeal protein-bound and one that is 70% protein-bound, but Maryland
Therapies at .80% protein binding clearance drops sharply (8).
A number of parameters influence the ability of Protein binding is saturable: certain drugs (salicylates, Correspondence:
extracorporeal therapies to remove poisons; the ideal valproic acid, carbamazepine, and phenytoin, among Dr. Joshua David King,
Division of
dialyzable substance is a small molecule, has a low others) have high protein binding at therapeutic Nephrology and
volume of distribution, low protein binding, and rapidly concentrations, which limits dialyzability, but become Maryland Poison
distributes from tissue to plasma (3,5–7). Table 1 explores amenable to removal at various toxic concentrations Center, University of
these alongside different extracorporeal modalities. after binding sites are occupied and free drug levels Maryland School of
Medicine, 220 Arch
To clear any substance from the body extracorpo- rise (9–12).
Street, Baltimore, MD
really, it must be present in appreciable quantity in Improvements in HD, which have been made to 21201. Email:
the intravascular space; thus, volume of distribution clear greater amounts of uremic toxins, particularly JDKing@som.
is typically the greatest determinant of extracorporeal middle molecules, have increased the molecular mass umaryland.edu
removal of poisons. The volume of distribution, a of substances amenable to extracorporeal removal; for
theoretical volume which represents how much of a HD, conventional dialyzers may clear substances up
substance is present in plasma versus other spaces, to 15,000 Da, whereas high-cutoff hemofilters may

www.cjasn.org Vol 14 September, 2019 Copyright © 2019 by the American Society of Nephrology 1
2 CJASN

Table 1. Utility of extracorporeal modalities in poisoning

Toxin Toxin Volume Protein Examples of

Primary Limitations
Modality Molecular of Distribution Binding Toxins Amenable
of Therapy
Mass (Da) (L/kg) of Toxin to Therapy

Hemodialysis Up to 10,000– #1.5–2 #80% Salicylates, toxic Hemodynamic stability

15,000 alcohols, lithium
HCO filter HD Up to 50,000 #1.5–2 #80% Small peptide therapeutics; Limited availability
any therapy amenable Limited role in
to HD poisoning
CRRT Up to 15,000– #1.5–2 #80% Lithium Slow toxin clearance
25,000 (excepting toxins with
slow redistribution)
Hemoperfusion Unclear, but #1 L/kg Any Valproic acid, Limited availability
high carbamazepine Clotting
Hypocalcemia
Plasma exchange No limit #1 L/kg Any Monoclonal antibodies, Limited availability
arsine Very slow clearance

HCO, high-molecular-mass cutoff; HD, hemodialysis; CRRT, continuous renal replacement therapy.

clear substances closer to 50,000 Da in size (5,6,13,14). of toxin. Utilizing a large overdose of methanol (serum level
Plasmapheresis may clear substances of any size (15). 400 mg/dl) as an example, in an 80 kg man, intermittent HD
As toxins are removed from plasma via HD, they diffuse (2.5 m2 dialyzer, blood flow 400 ml/min, dialysate flow 800
from tissue along their concentration gradient. Although ml/min) would take nearly 8 hours to lower serum concen-
most dialyzable substances move relatively quickly from trations to 20 mg/dl, whereas high-dose continuous veno-
tissue to plasma, certain toxins exhibit slower transit, leading venous HD (dialysate flow 6000 ml/min) would require
to the phenomenon of “rebound,” where plasma levels of a almost 48 hours to achieve this (20).
given substance will increase hours after dialysis. Lithium is A complicated issue not fully addressed in this review is
the best-known example, although others (metformin, meth- when to consider the use of extracorporeal therapies for
otrexate, vancomycin, dabigatran, etc.) may exhibit rebound poisoning. There are relatively few drugs and other toxins
after extracorporeal removal (16,17). amenable to extracorporeal removal, and some dialyzable
Optimization of extracorporeal removal of poisons poisonings rarely require this (e.g., acetaminophen). In
depends primarily on increasing the volume of plasma addition, some toxins have greater endogenous clear-
filtered. Consider HD, where increasing blood flow rate, ance (kidney, hepatic, or otherwise) than extracorporeal
dialysate flow rate, dialyzer surface area, and time maximize elimination can provide, reducing the added value of the
toxin removal (18,19). This process is not linear: doubling procedure; Table 3 displays suitability of extracorporeal
therapy time does not result in removal of twice the amount removal for a variety of drug classes. The risks of the

Table 2. Sample pharmacokinetic characteristics of toxins

Optimal
Volume of Speed of
Molecular Protein Extracorporeal
Toxin Distribution Distribution from Dialyzability
Mass (Da) Binding Modality for
(L/kg) Plasma to Tissue
Removal

Amitriptyline 277 19 95% Fast Not dialyzable None

Colchicine 399 5–8 40% Fast Not dialyzable None
Ethylene glycol 62 0.6–0.8 Little to none Fast Dialyzable HD
Lithium 7 0.6–0.9 Approximately Slower, may have Dialyzable HD; CRRT
10% rebound after (nonemergent
HD cases)
Metformin 129 1–5 None Slower, may have Moderately HD
rebound after dialyzable
HD
Methotrexate 454 0.8–2 35%–50% Slower, may have Moderately HD
rebound after dialyzable
HD
Rituximab 144,000 ,0.2 None Not applicable Not dialyzable Plasma exchange
Vancomycin 1449 ,0.4–1 ,60% (varies) Slower, may have Moderately HD
rebound after HD dialyzable

HD, hemodialysis; CRRT, continuous renal replacement therapy.

CJASN 14: ccc–ccc, September, 2019 Extracorporeal Removal of Poisons and Toxins, King et al. 3

lipophilic substances, are potential exceptions (21). Occa-

sionally, CRRT may be used for convenience between HD
sessions; although logistically more difficult to achieve,
prolonged HD with more rapid toxin removal over time
may be preferable for toxins (e.g., caffeine, salicylates)
where rapidity of clearance may greatly affect the clinical
course (3,12). Recent reports suggest that extracorporeal
therapies are being used increasingly for supportive care of
AKI in poisonings not amenable to extracorporeal removal.
On the basis of current epidemiology, opioids and other
sedative-hypnotic agents causing shock, sympathomi-
metics (e.g., cocaine) causing rhabdomyolysis and AKI,
and severe acetaminophen poisonings (which may result in
AKI and multiorgan failure) are some of the more common
Figure 1. | Removal of toxins via HD decreases with greater de- nondialyzable toxins receiving dialysis; it is likely that
grees of protein binding. Comparison of removal of three uremic CRRT is often the therapy used in such cases (2,22).
toxins (p-cresyl glucuronide, 13% protein-bound; indole 3-acetic acid, Hemoperfusion, utilizing charcoal or resin-containing
73% protein-bound; and p-cresyl sulfate, 95% protein-bound) during hemofilters, has traditionally been used primarily for
a single HD session averaged over ten patients. Blood flow rates were poisoning; today, use has declined to roughly 1% of HD
300 ml/min, dialysate flow rates were 700 ml/min, and dialyzer urea utilization in the United States (2). This likely reflects
clearances varied. Modified from reference 8, with permission. improvements in HD technique and availability, frequent
complications of hemoperfusion (clotting, hypocalcemia,
procedure need to be balanced against the risks of toxicity. etc.), and cartridge cost (18,23). Other than for treatment of
Optimal use of extracorporeal therapies for poisoning paraquat poisoning (largely in Asia, and often in combi-
generally involves performing the procedure emergently nation with HD), hemoperfusion has little utility in treat-
and maximizing the rate of toxin removal, particularly ment of poisonings nowadays (3,24).
when a toxin produces life-threatening or irreversible Apheresis has utility in a relatively small number of
toxicity. When needed, we would recommend to consider poisonings, but has the advantage of removing toxins
the involvement of a medical or clinical toxicologist, as that may be impossible to remove via other methods (15).
not all nephrologists are comfortable managing difficult Poisons removed via apheresis optimally have very low
or rare forms of poisoning cases. Further, most nephrol- volumes of distribution, as a lower volume of blood is
ogists are rarely called to manage poisoning cases except processed during a single apheresis treatment than
when kidney replacement therapy is needed, and toxi- during a standard HD treatment. Exchange transfusion
cologists may aid in managing aspects of poisoning other and therapeutic plasma exchange have been utilized for
than extracorporeal therapy utilization; for example, rare poisonings not otherwise amenable extracorporeal
glucarpidase (an enzyme which rapidly and effectively removal, such as snake envenomation, iatrogenic poison-
breaks down methotrexate) may be used instead of or in ing with monoclonal antibodies, arsine gas, and Amanita
addition to HD in the treatment of methotrexate poison- phalloides (a highly poisonous basidiomycete mushroom)
ing in patients with AKI (3). poisoning, but it is unclear how much benefit is gained via
these procedures (15,25,26).
Albumin dialysis refers to HD (typically CRRT) against a
Modalities of Extracorporeal Therapy for Poisoning dialysate that contains circulating albumin, and is utilized
Although HD is the preeminent extracorporeal modality primarily as support in liver failure (3,27). Although such
utilized for poisoning, other modalities include continuous systems can theoretically be useful to remove protein-
RRT (CRRT), hemoperfusion, therapeutic plasma ex- bound toxins, and case reports of use in poisoning exist,
change, exchange transfusion, and albumin dialysis (3). albumin dialysis typically is inferior to HD at clearing
Comparison between these modalities is addressed in poisons, with clearances of a number of protein-bound
Table 1. As clearance of greater volumes of plasma will drugs (e.g., phenytoin, valproic acid) that are typically
increase toxin removal, HD is the optimal choice for nearly lower than that achievable by HD (3).
all toxins amenable to extracorporeal removal. Peritoneal
dialysis is not addressed in this review, primarily because
its clearance of toxins is very slow; it should only be used Extracorporeal Treatment for Individual Toxins
if all other extracorporeal modalities are unavailable in The use of extracorporeal therapies for poisoning has
resource-limited settings (3,4). steadily grown over the past 50 years (2). In the United
Although studies are scarce, CRRT use for poisoning has States, best-available data suggest that extracorporeal
significantly increased; this is likely because of the ease of treatment is performed in 0.45% of poisoning exposures;
the procedure, especially in the context of shock (2). detailed information (from the American Association of
Unfortunately, because of slow blood and dialysate flow Poison Centers) is only available for roughly one fourth
rates, CRRT has limited utility for the treatment of of these cases (2,28). Across different Western countries,
poisoning and should be foregone in most cases in favor ethylene glycol, lithium, and salicylates have consistently
of HD; lithium and other substances with slow movement comprised roughly two thirds of poisonings treated via
from tissue to plasma, including some moderately extracorporeal therapies (2).
 4
CJASN
Table 3. Dialyzability of selected toxins by therapeutic class

Selected Agents Selected Agents

General
Therapeutic Class/ Amenable to Not Amenable to
Examples Pharmacokinetic
Group of Poisons Extracorporeal Extracorporeal
Properties
Removal Removal

Antiarrhythmics Amiodarone, flecainide, lidocaine, Lipophilic with high volume of Sotalol (HD) Amiodarone, flecainide, lidocaine
sotalol distribution, protein binding
Anti-diabetic medications Insulin, metformin, sulfonylureas Varied Metformin (HD) Insulin, sulfonylureas
Antidepressants and Amitriptyline, haloperidol, Lipophilic with high volume of Lithium (HD, CRRT) SSRIs/SNRIs, TCAs, antipsychotics
antipsychotics quetiapine, sertraline distribution, protein binding
Antiepileptics Barbiturates, benzodiazepines, Varied; generally at least Barbiturates (HD); after massive Benzodiazepines, lamotrigine
carbamazepine, phenytoin moderately lipophilic ingestion, carbamazepine,
phenytoin, valproic acid (HD)
Antimicrobials Antifungals, antivirals, b-lactams, Varied Cefepime, vancomycin (HD) Amphotericin
glycopeptides
b-Adrenergic receptor blockers Acebutolol, atenolol, carvedilol, Varied Acebutolol, atenolol, metoprolol (HD) Most agents; carvedilol, propranolol,
labetalol, metoprolol labetalol
Calcium channel blockers Amlodipine, diltiazem, Lipophilic with high volume of None Amlodipine, diltiazem, nifedipine,
nifedipine, verapamil distribution, protein binding verapamil
Cardiac glycosides Digoxin, plant toxins (e.g., oleandrin) Lipophilic with high volume of None All
distribution, protein binding
Chemotherapeutic agents Cisplatin, methotrexate, rituximab, Varied Methotrexate (HD), rituximab, Vincristine, doxorubicin
vincristine, doxorubicin cisplatin (plasma exchange)
Methylxanthines Caffeine, theophylline Hydrophilic with low volume All None
of distribution, low protein
binding
Oral anticoagulants Apixaban, dabigatran, rivaroxaban, Most lipophilic with high Dabigatran (HD) Apixaban, rivaroxaban, warfarin
warfarin volume of distribution,
protein binding
Sympathomimetic agents Cocaine, amphetamines, synthetic Lipophilic with high volume of None Cocaine, amphetamines, synthetic
cathinones (“bath salts”) distribution, protein binding cathinones

HD, hemodialysis; CRRT, continuous renal replacement therapy; SSRIs, selective serotonin reuptake inhibitors; SNRIs, serotonin-norepinephrine reuptake inhibitors; TCAs, tricyclic anti-
depressants.
CJASN 14: ccc–ccc, September, 2019 Extracorporeal Removal of Poisons and Toxins, King et al. 5

Figure 2. | Toxic alcohol metabolic pathways with mechanisms of toxicity of parent compounds and metabolites. Parent compounds and
metabolites causing toxic effects (detailed at bottom of figure) are represented in red font. ADH, alcohol dehydrogenase; ALDH, aldehyde
dehydrogenase; a2AR, a-2 adrenergic receptor; CNS, central nervous system; LDH, lactate dehydrogenase.

Extracorporeal treatment of commonly dialyzable toxins is removal is often ideal given the high cost of fomepizole and
discussed below; the literature does not provide robust prolonged hospitalization (32).
evidence for extracorporeal treatment of poisoning, and Similar to other toxic alcohols, methanol and metabolites
optimal treatment would involve a nephrologist and medical are well removed via HD. HD clears methanol at roughly
toxicologist working in concert for most dialyzable poison- 200 ml/min, cutting the t1/2 to below 4 hours; importantly,
ings. The Extracorporeal Treatment in Poisoning (EXTRIP) the same is true of HD clearance of formic acid (31,32). The
workgroup, an international, multidisciplinary group that EXTRIP workgroup recommends extracorporeal treatment
systematically reviewed the literature published concerning for severe methanol poisoning with acidemia, seizures, or
extracorporeal therapies for poisoning, has published the vision deficits, or for serum concentrations .70 mg/dl after
most evidence-based, thorough recommendations regarding fomepizole; as most clinicians will not have access to real-
extracorporeal treatment of poisoning; their work is available time toxic alcohol levels, the osmolality gap (discussed
at www.extrip-workgroup.org (29). below) may need to substitute for this (31). Because of the
latent period between intoxication and onset of symptoms,
as well as potential irreversibility of toxicity, early use of
Methanol dialysis may need to be considered in concerning methanol
Methanol is widely used in a variety of products ranging ingestions.
from windshield wiper fluid, racing car fuel, to camping
fuel, and in a number of industrial settings; outbreaks may
also occur from tainted homemade ethanol (“moonshine”). Ethylene Glycol
Like other toxic alcohols, it is metabolized by alcohol Ethylene glycol is primarily used as antifreeze and in
dehydrogenase and aldehyde dehydrogenase into formal- chemical manufacture. A small alcohol with two hydroxyl
dehyde and formic acid, respectively (Figure 2), which both groups, it is metabolized via alcohol dehydrogenase,
cause direct mitochondrial toxicity (30,31). The toxic effects aldehyde dehydrogenase, and lactate dehydrogenase. Al-
of methanol metabolites are most prevalent in the central though oxalate is the metabolite primarily responsible for
nervous system (CNS), where a variety of sequelae such as end-organ toxicity, glycolic acid is mostly responsible for
blindness, coma, and paresis may result; unfortunately, these metabolic acidosis (33,34). Clinical effects due to ethylene
are secondary to neural tissue death and are often poorly glycol poisoning include sedation and coma (due to
reversible (30,31). Although the alcohol dehydrogenase in- parent compound), AKI, and occasionally CNS and myo-
hibitor fomepizole is commonly used to treat toxic alcohol cardial damage. The latter effects are due to precipitation
poisonings, it does not remove these (readily dialyzable) toxic of calcium oxalate crystals, which directly damage tissue;
metabolites (31,32). After fomepizole administration, en- although most commonly seen in kidney tubules where
dogenous methanol clearance is exceedingly slow, with oxalate concentrations are highest, in massive ingestion
a t1/2 of roughly 50 hours; aggressive extracorporeal these crystals may form in other tissues (33–35).
6 CJASN

As access to real-time serum levels is uncommon, diagnosis therapy in salicylate poisoning is progressive toxicity despite
of ethylene glycol poisoning commonly relies upon measuring appropriate medical treatment (e.g., intravenous sodium
an osmolality gap between calculated and measured serum bicarbonate).
osmolality (33). Notably, this method may miss small
ingestions of ethylene glycol and serial chemistries ob-
Acetaminophen (Paracetamol)
serving for development of acidosis may be of use. Point-
Although acetaminophen is readily dialyzable, most
of-care blood gas analyzers, which commonly utilize the
acetaminophen poisonings do not require extracorporeal
enzyme lactate oxidase, may misread chemically similar
removal because of the effectiveness of N-acetylcysteine
glycolic acid as lactate and return a falsely elevated serum
(NAC) for early presentations (43,44). Classically, severe
lactate level; the “lactate gap” resulting from the differ-
acetaminophen poisoning results in acute liver failure.
ence between serum and whole blood lactate may be
However, in extremely large overdoses, acetaminophen
diagnostically useful if ethylene glycol intoxication is
may produce encephalopathy and lactic acidosis; this may
suspected (36).
be due to mitochondrial injury from acetaminophen itself,
Ethylene glycol and its metabolites are readily dialyz-
or locally elevated metabolite concentrations. Typically,
able. Clearance of ethylene glycol and metabolites via HD
this occurs at acetaminophen concentrations .750 mg/L
results in an elimination t1/2 under 3 hours (34). Although
(43). The effectiveness of NAC is not well established for
virtually all published recommendations suggest HD for
these scenarios, and extracorporeal removal may have
severe acidemia or AKI after ethylene glycol poisoning, in
clinical benefit in preventing toxicity.
recent years a number of cases have been treated with
The EXTRIP workgroup reviewed 22 case reports and
fomepizole alone given that endogenous kidney clearance
series, one observational trial, and one randomized, con-
results in a t1/2 of ,18 hours (37). Recent evidence-based
trolled trial comprising 127 patients; they concluded that
recommendations for when to perform extracorporeal
there was sufficient evidence to suggest extracorporeal treat-
therapy for ethylene glycol are not available; consideration
ment of severe acetaminophen poisoning, with a recommen-
should be given to massive ingestions without acidemia,
dation to treat levels .900 mg/L in patients with altered
particularly as ethylene glycol itself may cause coma.
mental status and lactic acidosis who are receiving NAC (43).
It should be noted that NAC dosing may need alteration
Other Toxic Alcohols during dialysis (43).
Other than methanol and ethylene glycol, a number of
short-chain alcohols may cause toxicity that may warrant
consideration of extracorporeal removal. Short-chain alco-
Lithium
Despite more than a century of clinical use, lithium’s
hols share similar pharmacokinetic parameters with meth-
mechanism of toxicity remains poorly understood (16,45).
anol and ethylene glycol, and as a rule are quite amenable
Although lithium may cause comparatively mild gastro-
to extracorporeal removal. Some of these alcohols are
intestinal and cardiac toxicity, its major site of therapeutic
summarized briefly in Figure 2. Other than ethanol and
and toxic action remains the CNS (16,45). Ataxia, myoclo-
isopropanol, HD and fomepizole are commonly used to
nus, and tremor are most commonly seen with lithium
treat these poisonings (38–40).
toxicity; severe symptoms include seizures, delirium, and
coma, with fatalities stemming from severe neurotoxicity.
Salicylates Clinical presentation does not correlate well with lithium
Readily dialyzable, salicylic acid was one of the first levels (16).
compounds removed via HD during early 20th century It is recommended practice that seizures, arrhythmias, or
trials (1). Salicylates cause toxicity through multiple mech- coma related to lithium toxicity should receive extracor-
anisms, the primary one being uncoupling of mitochon- poreal therapy. Although the EXTRIP workgroup recom-
drial oxidative phosphorylation (12,41,42). The clinical mends extracorporeal therapy for lithium poisoning at
picture of salicylate poisoning is protean, with manifesta- concentrations .4.0 mEq/L with reduced kidney function,
tions ranging from tinnitus, vomiting, metabolic acidosis and suggests this for levels .5.0 mEq/L, there is a rela-
(from lactate, ketones, and salicylate itself), primary respira- tively low level of evidence for optimal treatment of lithium
tory alkalosis, agitated delirium, and/or somnolence; more even compared with other frequently dialyzed toxins, and
severe presentations may include acute respiratory distress clinical practice varies significantly (16).
syndrome, AKI, hyperthermia, seizures, and shock (41,42). Lithium has a low molecular mass, volume of distribu-
Fatalities are usually due to cerebral edema. Poisonings tion, and protein binding; it is readily removed from
may be easily misdiagnosed (e.g., as sepsis), and events plasma by HD (3,4,16). Unlike most toxins, however,
that lower blood pH (such as seizures or medications that lithium travels from cells to plasma via sodium channels,
slow the respiratory rate) may provoke rapid shifts of and thus equilibrates more slowly than nearly all other
salicylate across the blood-brain barrier, worsening toxic- dialyzable toxins, which directly diffuse across cell mem-
ity acutely (41,42). Early consideration of HD is critical in branes; its extracorporeal removal is analogous to electro-
severe salicylate poisoning. lytes such as phosphate (3,16). As a result, repeat HD
The EXTRIP workgroup reviewed extracorporeal treat- sessions are commonly needed as rebound of plasma levels
ment for salicylate poisoning; they recommend extracor- is seen several hours after therapy (3,4,16). CRRT may be
poreal therapy for salicylate concentrations .100 mg/dl, as used to avoid the issue of rebound, although caution is
well as altered mental status and hypoxemia (12). However, advised to consider HD initially in severe toxicity for
perhaps the most compelling indication for extracorporeal rapid resolution of life-threatening symptoms.
CJASN 14: ccc–ccc, September, 2019 Extracorporeal Removal of Poisons and Toxins, King et al. 7

One of the more severe complications of lithium toxicity medical toxicologist or a poison center for optimal care of
is permanent neurotoxicity; it is unclear whether extracor- these patients is advised.
poreal treatments affect this (45). Case series are conflicting
on whether neurotoxicity is less common or more common Disclosures
after extracorporeal therapy, and it is uncertain if rapid Dr. Jaar reports receiving royalties from UpToDate for writing
removal of lithium avoids or increases the risk of long-lasting a chapter on “Lead-Related Nephrotoxicity” outside of the sub-
sequelae (45,46). mitted work. Dr. Kern and Dr. King have nothing to disclose.

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