INTRODUCTION
Lithium first saw clinical use as a means to reduce uric acid
concentrations in patients with gout. The mood-altering effects of
lithium led internist Alfred Baring Garrod to erroneously infer the
presence of “brain gout” in 1859. In 1871, William Hammond first
described the use of Lithium for mania, but widespread adoption did not
follow until the mid-20th century.[1]
Despite having decades of proof as an effective treatment for bipolar
disorders, lithium use is hampered by a narrow therapeutic index, and
toxicity is common. The manifestations of toxicity vary based on acuity
of exposure, with gastrointestinal manifestations predominating in acute
overdose and neurologic manifestation in chronic accumulation, either by
over medication or reduced elimination. Following lithium toxicity, some
patients develop prolonged or permanent neurological sequelae, known as
the Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT),
which spans a spectrum of neurological symptoms from mild tremors to
debilitating cognitive and motor impairments.[2] While the risks for
the development of long-term sequelae are not well characterized, there
is an association between the duration of elevated serum lithium
concentrations (reflecting a high CNS lithium concentration) and an
increased likelihood of serious or prolonged symptoms.[3] It follows
that expeditious removal of lithium from the body may limit long-term
toxicity.
Lithium is well suited for removal by hemodialysis. It is a small
molecule, with minimal protein binding and a volume of distribution of
0.7-0.9 L/kg.[4] While it is undisputed that hemodialysis removes
lithium, the clinical efficacy of hemodialysis has not been definitively
established by well-designed randomized controlled trials. As such,
identifying patients likely to benefit from hemodialysis is challenging.
The Extracorporeal Treatments in Poisoning Workgroup published a
systematic review of the literature in 2015 and established expert
consensus guidelines on the use of hemodialysis in lithium poisoning.
Despite expert consensus, all suggestions and recommendations were based
on very low levels of evidence.[5] The EXTRIP guidelines have never
been externally validated.
Seeking to hone these guidelines with the aim of reducing potentially
unnecessary treatments, a retrospective analysis of 128 ICU patients
with lithium toxicity identified a lithium concentration ≥5.2 mmol/L or
creatinine ≥200 µmol/L as indicators for hemodialysis.[6] On a
subsequent analysis, these “Paris” criteria were applied
retrospectively to the same cohort, and compared to EXTRIP criteria. For
each set of criteria, neurological status at ICU discharge was compared
between patients who met the criteria and underwent ECTR and those who
met the criteria but did not undergo ECTR.[7] The authors conclude
that the application of Paris criteria led to a statistical difference
in outcome in the primary analysis, and that application of the EXTRIP
criteria leads to ECTR in more patients than is necessary, although they
acknowledge modifications to the published EXTRIP criteria used in their
analysis and the inherent circular nature of validation of the Paris
criteria using the derivation cohort.
To our knowledge, neither EXTRIP nor Paris criteria have been
independently validated or compared. In this study we applied both
EXTRIP and Paris criteria retrospectively to a cohort of patients in a
poison center database to determine if differences in neurologic
outcomes were significant in cases in which criteria were discordant.