The Role of the Nephrologist in

Management of Poisoning and

Intoxication: Core Curriculum
2022

Michael E. Mullins and Jeffrey A. Kraut

Introduction

In 2019, AAPCC recorded 2.1 million cases of human

exposure to poisons.

The nephrologist  necessary to manage severe acid-

base disorders, electrolyte abnormalities, or kidney
dysfunction.

This article will discuss the pathophysiology, diagnosis,

and treatment of acute and chronic poisonings
Toxic Alcohols
EPIDEMIOLOGY

2019 AAPCC report  isopropanol was the most frequent cause of toxic alcohol poisoning (16,000 cases
reported)  followed by ethylene glycol and methanol.
Toxic Alcohols
P AT H O G E N E S I S

Except for isopropanol, the injurious effects of the toxic alcohols primarily result from
accumulation of their toxic acid metabolites.
Toxic Alcohols
C L I N I C A L F E AT U R E S
Accumulation of their toxic metabolites produces
organ dysfunction.
• Methanol intoxication  impairs vision and can
produce permanent blindness in some cases
• Pulmonary dysfunction, abdominal pain, coma,
and Parkinson-like symptoms
• The clinical abnormalities usually evolve over 6 to
24 hours
• Coingested ethanol  delay toxic effects.
Ethylene glycol metabolism forms:
• Glycolic acid  the principal cause of
acidosis.
• Oxalate crystals  organ dysfunction
including acute kidney injury (AKI).
Neurologic dysfunction  the first 12 hours 
followed by cardiac and pulmonary dysfunction
in the next 12 hours  AKI at 48 to 72 hours
after exposure
Toxic Alcohols
C L I N I C A L F E AT U R E S

Isopropanol intoxication
• Depresses the sensorium
• Respiratory dysfunction
• Cardiovascular collapse
• Acute pancreatitis
• Hypotension-induced lactic acidosis

Diethylene glycol
• Abdominal pain
• Nausea, vomiting, diarrhea, hepatic disease
• Acute pancreatitis
• Altered mental status, central and peripheral neuropathy
(occasionally causing quadriplegia)
• AKI, and death.
 Toxic Alcohols
DIAGNOSIS

The presumptive diagnosis of toxic alcohol poisoning

usually rests on
Definitive diagnosis of methanol and ethylene
• A report of possible exposure in association with the glycol uses high performance gas or liquid
chromatography.
aforementioned symptoms
• Physical findings This process is labor intensive, expensive, and
• Characteristic blood chemistry abnormalities not available in most clinical laboratories.
• High serum osmolality
• High anion gap metabolic acidosis Results can take several hours/days.

The 2 methods of measuring serum osmolality:

1. Freezing point depression
2. Vapor pressure osmometry
Algorithm for the
diagnosis and
treatment of
methanol, ethylene
glycol, and
isopropanol
intoxications
Toxic Alcohols
T R E AT M E N T
Salicylate Intoxication
EPIDEMIOLOGY

Salicylate intoxication: acute or chronic.

Acute salicylate intoxication 

• ingestion of ≥100 - 150 mg/kg salicylate or
• ingestion of small amounts of methyl salicylate

Repeated topical use of topical analgesic cream (up

to 30% methyl salicylate) may cause serious poisoning

The most common source of salicylate poisoning is

acetylsalicylic acid or aspirin

Chronic poisoning  more common in elders  preexisting kidney

disease/compromise of
kidney function
Salicylate Intoxication
PAT H O G E N E S I S

Salicylates directly stimulate the respiratory center of the medulla

Increase in both the rate and depth of Uncouple oxidative phosphorylation  inhibit
respiration resulting in respiratory citric acid cycle dehydrogenases  a shift to
alkalosis. increased glycolysis.

Generation of lactic acid and stimulation of hormone-sensitive lipase

Increased lipolysis and increased ketone production.

Salicylate Intoxication
C L I N I C A L F E AT U R E S

Patients with acute salicylate intoxication can present

with
• Confusion
• Agitation A chest radiograph  pulmonary opacities.
• Disorientation that can progress to coma
• Shortness of breath Agitation, confusion, hallucinations, slurred speech,
• Tinnitus (or other hearing disturbances) seizures, and coma appear  more frequent in those
with chronic salicylate poisoning
Physical findings can include:
A delay in diagnosis and initiation of therapy  higher
• Hyperventilation
morbidity for chronic intoxication
• Evidence of volume depletion
• Noncardiogenic pulmonary edema
• Hematemesis and petechiae
Salicylate Intoxication
C L I N I C A L F E AT U R E S
Prominent laboratory abnormalities include acid-base
disturbances.
In children  early, transient respiratory alkalosis followed
by metabolic acidosis.
Less commonly, a normal anion gap metabolic
acidosis can develop due to
• Excretion of sodium and potassium salts in the urine
• Subsequent retention of chloride.
T R E AT M E N T
Aggressive volume resuscitation with NS
or RL
Once euvolemia is achieved, large
quantities of fluid to induce forced diuresis
is not recommended.
Oral activated charcoal reduces further
salicylate absorption when given within 1
to 2 hours
Salicylate Intoxication
T R E AT M E N T

• Hemodialysis the fastest and most effective method of eliminating salicylate

• Hemodialysis should occur early when indications are present.

• Delaying hemodialysis increases mortality.

I N D I C AT I O N O F
H E M O D I A LY S I S
Acetaminophen
EPIDEMIOLOGY

Acetaminophen (paracetamol)  the most frequent

pharmaceutical agent involved in human poisonings.

It accounts for approximately 5% of the over 100,000

cases reported annually

It remains a leading cause of poisoning death

Pathogenesis
Overdoses of acetaminophen
saturate the glucuronide and
sulfate conjugation pathways
Larger fraction of the drug
undergoes oxidation (mainly
by CYP2E1) to NAPQI.
NAPQI  potent oxidant 
binds (-SH) groups on
intracellular proteins 
denaturation  hepatocellular
injury.

Clinical Findings
• 1st day  the patient may have nausea and abdominal pain/asymptomatic.

• Rising AST and ALT activities  apparent on day 2, with peak values around day 3.
• INR may rise about 1 day after the rise in AST and ALT.

• Peak toxicity occurs around day 3 or 4.

• Severe cases may have hepatic encephalopathy and cerebral edema.
DIAGNOSIS T R E AT M E N T

No early signs or symptoms  the diagnosis depends upon The main therapeutic measures:
the serum acetaminophen concentration.
1. Supportive care
The Rumack-Matthew  determines the risk of
hepatotoxicity by plotting serum acetaminophen 2. Administration of NAC  sulfhydryl
concentration versus time donor directly reduces NAPQI and
repletes glutathione.
If the acetaminophen concentration > 150mg/L
(993 μmol/L) at 4 hours  the patient should receive
antidotal NAC
Metformin
EPIDEMIOLOGY
Metformin-associated lactic acidosis (MALA)
• 3 to 10 cases per 100,000 patient-years.

• Mortality  61% in some cases.

• Predisposing conditions include hepatic and acute or chronic
kidney disease

PAT H O G E N E S I S

Metformin inhibits glycerol-3-phosphate dehydrogenase and the

glycerophosphate shuttle

the mitochondrial redox state

↑the cytosolic redox state

Reducing conversion of lactate to pyruvate

Metformin

CLINICAL FINDING T R E AT M E N T

Gastrointestinal symptoms Sodium bicarbonate to treat the acidemia

and supportive therapy to stabilize the blood pressure.
Severe cases 
• Serious hemodynamic instability Early hemodialysis is the most effective therapy
• Depressed consciousness
• Abdominal tenderness may mimic an
acute abdomen.

Laboratory findings
• Elevated lactate concentrations (>5
mmol/L) and acidemia.
Lithium

Lithium (usually as lithium carbonate) has a very narrow

therapeutic range (serum [Li+] 0.6 - 1.3 mmol/L)

Li+  sensitive to modest changes in kidney function.

Acute-on chronic Li+ toxicity most often results from

AKI/rapid escalation of the dose.

Acute overdose can rapidly produce high lithium

concentrations
 Lithium

When measuring [Li+], using the wrong tube produces an

unexpectedly high apparent concentration.

If the laboratory uses a green-top tube to measure

lithium, the lithium heparin will produce a factitious
elevation in the apparent [Li+].
Thank You