Poisonings & IntoxicantsWhat a Nephrologist Needs to Know

Timothy B. Erickson, MD, FACEP, FACMT, FAACT

Chief, Division of Medical ToxicologyDepartment of Emergency Medicine

Brigham & Women’s HospitalHarvard Medical School

Harvard Humanitarian Initiative

Timothy B. Erickson, MD, FACEP, FACMT, FAACT

• University of Health Sciences / Chicago Medical School

• Emergency Medicine Residency University of Illinois @ Chicago

• Medical Toxicology Fellowship Cook County Hospital / University of Illinois @ Chicago

• Associate Professor of Emergency Medicine Mass General Brigham / Harvard Medical School

Financial Disclosures

NIH NIDA SBIR (R44DA051106) grant Co-I

“A novel robotic wastewater analysis system to quantify opioid exposure and treatment in residential communities”

Massachusetts Consortium for Pathogen Readiness (MassCPR) grant P-I

“Wastewater-based epidemiology to rapidly diagnose and map the COVID-19 pandemic.“

Medical advisor/consultant for Biobot Analytics, Cambridge, MA, a company engaged in the collection and analysis of wastewater to develop epidemiological data. Dr. Erickson’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict of interest policies.

Toxic Nephrology Question

Which of the following poisons is hemodialysis considered ineffective in the overdose setting?

A. Lithium

B. Salicylates

C. Ethylene Glycol

D. Cyclic Antidepressants

E. Metformin

OBJECTIVES

• Discuss various patient overdoses which present in the clinical setting with potential renal toxicity.

• Describe subtle, can’t miss clues to lethal overdoses, including metabolic and nephrogenic derangements

OBJECTIVES

• Discuss current management and extracorpreal treatment strategies for a variety of toxicology cases.

• Describe criteria used in choosing one treatment over another for managing a variety of critically ill overdosed patients.

Principles of Toxicology

• Reduce exposure

• Reduce absorption

• Increase elimination

• Know when to intervene

• Give supportive care

• Give specific therapy and antidotes when appropriate

DRUG DIALYZABILTY

• Molecular weight

• Protein binding

• Water solubility

• Volume of distribution

• Plasma clearance

• Elimination

• Bioavailability

CASE #1

• A 44 yr old male is brought to the ED with altered mental status

• Earlier that week he had been laid off from his laboratory job as a chemist.

CASE #1

• Vitals: HR= 100; BP: 90/60; RR=24

• Temp = afebrile; Pulse ox= 95%

• Patient is orally intubated & given IVFs

• Labs: pH=6.95; PCO2=24; PO2=169; HCO3= 8; Na=142; K=3.9; Cl=108

• LA: 23

METABOLIC ACIDOSISELEVATED ANION GAP

M METHANOL, METFORMIN, MASSIVE ODE ETHYLENE GLYCOLT TOLUENEA ALCOHOLIC KETOACIDOSIS L LACTIC ACIDOSIS

A ACETAMINOPHEN C CO, CYANIDE, COLCHICINEI INH, IRON, IBUPROFEND DKA

G GENERALIZED SEIZURE DRUGSA ASA SALICYLATESP PARALDEHYDE, PHENFORMIN

CYANIDE FACTS

• Cyanide poisoning disrupts oxygen utilization and ATP production

• Poisoning causes a rapid onset of CNS and CV toxicity

• Lab clues include a lactic acidosis and diminished A-V O2 difference

THE KREB’S CYCLE & CYANIDE POISONING

CYANIDE FACTS

• Antidote therapy with hydroxycolbalaminshould be considered early in course

• Do not await cyanide levels

• Nitroprusside drips can result in cyanide toxicity

• Delayed onset of symptoms after oral nitrile ingestion

CASE #1 OUTCOME

• With severe anion gap acidosis and elevated lactic acidosis, a diagnosis of presumed cyanide toxicity was made.

• The patient was given hydroxocobalamin and was noted to have red skin soon after infusion

Wong SL, et al: Wine-colored plasma and urine

from hydroxocobalamin treatment. J Gen Intern

Med 2016

CASE #1 OUTCOME• In the ICU, the acidosis and mental status remained

unchanged after hydroxycobalamin administration.

• CO level was negative; serum ASA level was zero

• Confirmatory cyanide level was sent to a reference lab

• The patient’s spouse brought in an empty bottle of metformin the patient had been recently started on for new onset DM.

• Yamada T, et al: Lactic acidosis due to attempted suicide with metformin overdose: a case report. Diabetes Metab 2016

• Gupta A, Tiru B. Metformin-induced lactic acidosis-Did THAM do the trick? Crit Care Med 2015; 43: 322.

• Moioli A, et al: Metformin associated lactic acidosis (MALA): clinical profiling and management. J Nephrol 2016;

CASE #2

• A 51 year old female presented to the ED after being found unresponsive and surrounded by vomitus and unknown white pills. The time of ingestion was unknown

• In the ED she was acidotic, hypothermic and required oral intubation.

• Initial acetaminophen level =1121mcg/mL with a pH of 6.9

• Two 20 hr IV NAC regimens were completed but the patient expired on Day#4

• Villano JH et al. Coma and Severe Acidosis: Remember to Consider Acetaminophen. J Med Toxicol 2015 July

Treating massive APAP overdose with

hemodialysis

Altered mental status

Elevated lactate

Metabolic acidosis

APAP level > 900 mcg/mL

Marc Ghannoum, et al: Massive acetaminophen overdose: effect of hemodialysis

on acetaminophen and acetylcysteine kinetics. Clin Toxicol Apr 2016, 519-22.

MASSIVE OVERDOSES

• High mortality rate

• Metabolic acidosis

• Early hemodialysis should be considered

• Gastric decontamination parameters will be altered

Fatalities involving multiple medications are now

the most common type of fatal poisoning reported to

the AAPCC.

Peter W. Greenwald, et al: Increasing frequency & fatality of poison center

reported exposures involving medication & multiple substances: data from the

AAPCC 1984–2013. Clin Toxicol 2016.

CASE #3

• A 29 yr old female presents to the ED after ingesting “hundreds” of unknown tablets 8hr prior that the mother believes to be “Tylenol”

• The patient had episode of emesis at home with dark material noted.

• She reports mild abdominal pain

CASE #3

• On exam she appears pale

• Vs: HR= 135; BP=100/70; RR=24 T=99

• Lungs: CTA Ht: RRR S1S2

• Abd: epigastric tenderness (+)BS

• Urine pregnancy test (+)

CASE #3

• Labs:

• pH= 7.35/ PO2=109/ PCO2=25 HCO3=14

– Glucose=240

– WBC=18K

– US (+) for radiopaque tablets and 10week IUP

• Serum APAP: zero

• ASA level: 75mg/dL (8 hrs post)

Ultrasound and Tox

– Bothwell JD, et al: Effect of decontamination therapy on US visualization of ingested pills. West J Emerg Med 2014; 15:176-9.

CASE #3 OUTCOME

• After activated charcoal administration the patient vomits multiple pill fragments.

• A bicarbonate drip for alkalinization of the urine is initiated.

• Nephrology is consulted for possible hemodialysis

– Baudy A, et al: Salicylate toxicity: does alkalinizing urine work? J Invest

Med 2013; 61:441.

– Juurlink DN: Activated charcoal for acute overdose: A reappraisal. Br J Clin Pharm 2015.

Case #3 Outcome

• While awaiting hemodialysis, the patient becomes more tachypnic and lethargic.

• She is orally intubated after RSI agents are administered.

• One hour later she suffers a tonic-clonic seizure and goes into sudden cardiac arrest

Salicylates

• Srisuma S, et al: Missed opportunities?: an evaluation of potentially preventable poisoning deaths, Clin Toxicol Mar 2016; 441-46.

• Bauer S, et al: Salicylate toxicity in the absence of anion gap metabolic acidosis. Am J Emerg Med 2016

• Thompson TM, Toerne T, Erickson TB.Salicylate toxicity from genital exposure to a methylsalicylate-containing rubefacient. West J Emerg Med 2016; 17: 181-3.

CASE #4

• A 18 year old college freshman male drank several “Frankenstein shots” according to friends approximately 12 hours prior to presentation to the ED.

• He was transported by EMS obtunded with Kussmaul respirations.

CASE #4

• Vitals: BP= 90/60 HR=120

• ABG: 6.93; PCO2=17; PO2=76

• Woods lamp induced fluorescence of the gastric contents was noted in the ED

TOXIC ALCOHOLS

• Methanol ingestion associated with visual disturbances, metabolic acidosis and multi-system failure.

• Ethylene glycol poisoning associated with metabolic acidosis, hypocalcemia, renal failure and death.

Thanacoody, RHK, et al: Management of poisoning with ethylene glycol and methanol in the UK: a prospective study conducted by the National Poisons Information Service (NPIS). Clin Toxicol Nov, 2015

TOXIC ALCOHOL FACTS

• Isopropanol may cause CNS depression but does not usually cause metabolic acidosis.

• All of the toxic alcohols can produce an osmolal gap

• Fomepizole (4-MP) is the FDA approved antidote for EG and methanol

TOXIC ALCOHOLS

• Hemodialysis is indicated in severe toxic alcohol ingestions not responsive to conventional therapy, exhibiting severe acidosis, or end organ damage.

Nazir S, et al: Mind the gap: a case of severe methanol

intoxication. BMJ Case Rep 2016

CASE #4 OUTCOME

• A renal consult was obtained by the hospitalist and the patient was admitted to the ICU

• Fomepizole, sodium bicarbonate, thiamine and pyridoxine were given IV.

• The patient’s methanol level was zero and EG level was 662mg/dl

• He underwent hemodialysis for 4 hours with a post dialysis level of 202mg/dl

CASE #4 OUTCOME

• The patient developed V-tach 16 hours after admission, which responded to calcium, amiordarone and epinephrine

• The patient underwent another 4 hour round of hemodialysis

CASE #5HISTORY

• The patient is a 34 y/o male who is brought into the ED by his spouse who states her husband has been more "jittery" over the past 3 days with diarrhea.

HISTORY

• The patient has a history of bipolar disorder and recently had his lithium dose increased by his psychiatrist.

• Other medications include chlorpromazine and cogentin.

• The patient admits to occasional marijuana use but denies other drugs of abuse or heavy ethanol consumption.

• He denies any medication overdose or suicide attempt.

DIAGNOSTIC STUDIES

• CBC: WBC=13.5 H/H: 13/39• Lytes: Na=148 K=3.2 Cl=100 HCO3=28• Glucose: 190 BUN/Cr: 20/0.9

• Lithium level (serum): 3.2 mEq/L (NL=0.5-0.8)• Urine tox screen:(+)cannabinoids

CLINICAL COURSE

• The patient is admitted with a diagnosis of lithium toxicity to a monitored bed with a psychiatric consult.

• He is hydrated with IVFs and lithium is withheld.

LITHIUM LEVELS

REPEAT

• 12 hours later: 3.0 mEq/L• 24 hours: 2.9• 48 hours: 2.8• 72 hours: 2.8• 96 hours: 2.6

How do you account for this patient’s persistent lithium toxicity?

CLINICAL COURSE• The consistently toxic lithium levels despite

withholding the medication perplexes the medical service.

• The patient continues to demonstrate normal renal function.

• The chance of lab error is eliminated.

• Serum chlorpromazine level = 210ng/L (NL=150-300ng/L)

CLINICAL COURSE

• After further questioning and close observation, the possibility the wife may be surreptitiously poisoning her husband is ruled out.

CASE #6 CLINICAL COURSE

• On the 5th hospital day, the morning nurse enters the patient's room unannounced….

Vodovar D, et al: Lithium poisoning in the intensive

care unit: predictive factors of severity and indications

for extracorporeal toxin removal to improve outcome.

Clin Toxicol 2016

Dialyzable Toxins• STUMBLED

– Salicylates

– Theophylline

– Uremia

– Metformin/Methanol/Massive ingestions

– Barbiturates

– Lithium

– Ethylene glycol

– Depakote (Valproic acid)

Summary

• Discussed various patient overdoses which present in the clinical setting with potential renal toxicity.

• Described subtle, can’t miss clues to lethal overdoses, including metabolic and nephrogenic derangements

Summary

• Discussed current management and extracorpreal treatment strategies for a variety of toxicology cases.

• Described criteria used in choosing one treatment over another for managing a variety of critically ill overdosed patients.

Questions?

Poisonings & IntoxicantsWhat a Nephrologist Needs to Know

Timothy B. Erickson, MD, FACEP, FACMT, FAACT

Chief, Division of Medical ToxicologyDepartment of Emergency Medicine

Brigham & Women’s HospitalHarvard Medical School

Harvard Humanitarian Initiative