Types and management of Iatrogenic toxicity in ICU setting

1. Iatrogenic Toxicities in ICU
Acid Base Disorders (ABDs)
Zeinab Noormonavar
PharmD Candidate
1/29/2022
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3. Outline
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At the end of presentation we’ll be able to:
• Recall the pathophysiology, diagnosis, symptoms of ABD cause by
Iatrogenic toxicity.
• Identify the classification and pharmacological treatment modalities.
• Learn the different techniques used.

4. Definition
Iatrogenic:
From Greek; iatro (Healer) + genic (Producing)
Is the result of diagnostic and therapeutic procedures undertaken on a patient.
Disease or symptoms induced in a patient by the treatment or comments of a
physician.
4
Krishnan, N. R., & Kasthuri, A. S. (2005, January). Iatrogenic disorders. Medical journal, Armed Forces India. Retrieved January 29, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923397/

5. Sources of Iatrogenic Diseases
•Unjustified remarks
•Misinterpretation of
investigational
results
• Hospital
acquired
infection
• Drugs
• Surgery
• Any invasive
procedures
• Mechanical
• Radiological
Diagnostic
procedures
Therapeutic
regimen
Medical
team
Hospitalizati
on
5
Krishnan, N. R., & Kasthuri, A. S. (2005, January). Iatrogenic disorders. Medical journal, Armed Forces India. Retrieved January 29, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923397/

6. Risk Factors
Critical illness Comorbidities
Complex of
care
Increase
number of
administer
medications
6
Nazer, L. H., Brown, A. R. T., & Awad, W. (2021, June). Iatrogenic Toxicities in the Intensive Care Unit. Define_me. Retrieved January 29, 2022, from
https://www.criticalcare.theclinics.com/article/S0749-0704(21)00019-1/fulltext

7. Complications
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Acid base disorder
Electrolyte disorder
Methemoglobinemia Ototoxicity
Propofol related
infusion syndrome
Propylene glycol
toxicity
Renal toxicity
Rhabdomyolysis
Nazer, L. H., Brown, A. R. T., & Awad, W. (2021, June). Iatrogenic Toxicities in the Intensive Care Unit. Define_me. Retrieved January 29, 2022, from
https://www.criticalcare.theclinics.com/article/S0749-0704(21)00019-1/fulltext

8. Acid Base Disorders
• The most common complications encountered in the critically ill patient.
• Indicators for severe systemic disorders.
• In everyday clinical practice, analysis of ABDs must be performed in a
standardized manner.
• Highly sensitive diagnostic tools to distinguish the various ABDs include the
“anion gap” and the “serum osmolar gap”.
 AG=([Na+]+[K+])−([Cl−]+[HCO3−]) → 3-10 mEq/L
 OG= MO − CO → Normal= < 10 mOsm/kg
8
Kitterer, D., Schwab, M., Alscher, M. D., Braun, N., &amp; Latus, J. (2020, November 5). Drug-induced acid-base disorders . SpringerLink. Retrieved January 30,
2022, from https://link.springer.com/article/10.1007/s00467-014-2958-5

9. Diagnosis
ABG
AG
UAG
OG
ABD
9
UpToDate. (n.d.). Retrieved January 30, 2022, from https://www.uptodate.com/contents/approach-to-the-adult-with-metabolic-
acidosis?search=acid+base+disorders+management&amp;source=search_result&amp;selectedTitle=1~150&amp;usage_type=default&amp;display_rank=1#H17

10. Drug Induced ABDs Categories
• Drug-induced ABDs can be classified into five different categories in
terms of their pathophysiology:
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Metabolic
Acidosis
Base loss
Acid/Cl loss
→ Alkalosis
Exogenous
bicarbonate
loss
Respiratory
Alkalosis/aci
dosis
Kitterer, D., Schwab, M., Alscher, M. D., Braun, N., &amp; Latus, J. (2020, November 5). Drug-induced acid-base disorders . SpringerLink. Retrieved January 30,
2022, from https://link.springer.com/article/10.1007/s00467-014-2958-5

11. Metabolic Acidosis
Pathophysiology Drugs Induced
• Linezolid
• Metformin
• Propofol
• Valproic acid
• Propylene glycol
11
Nazer, L. H., Brown, A. R. T., & Awad, W. (2021, June). Iatrogenic Toxicities in the Intensive Care Unit. Define_me. Retrieved January 29, 2022, from
https://www.criticalcare.theclinics.com/article/S0749-0704(21)00019-1/fulltext
Mitochondrial toxicity
Type B lactic acidosis
Metabolized to Lactic
acid

12. Normal Anion Gap
• CAI
• ACEI
• Cyclosporine
• Heparin
• PSDs
• Tacrolimus
• Trimethoprim
• Pentamidine
• Amphotericin B
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Metabolic Acidosis (Cont’d)
Pathophysiology Drugs Induced
↘ HCO3 reabsorption in the proximal tubule
Hyperchloremic metabolic
acidosis
Inhibition of Na
reabsorption
Type 4 renal tubular
acidosis
Type 1 renal tubular acidosis
Kitterer, D., Schwab, M., Alscher, M. D., Braun, N., &amp; Latus, J. (2020, November 5). Drug-induced acid-base disorders . SpringerLink. Retrieved January 30,
2022, from https://link.springer.com/article/10.1007/s00467-014-2958-5

13. Clinical Manifestation:
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Metabolic Acidosis (Cont’d)
Change in
LOC
Kussmaul
respiration
Warm
flushed skin
Muscle
twitching
Decreased BP
Ventricular
arrhythmia
Hyperkalemia Headache
N/V/D
III, J. L. L. (2022, January 24). Metabolic acidosis - endocrine and metabolic disorders. MSD Manual Professional Edition. Retrieved January 30, 2022, from
https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/acid-base-regulation-and-disorders/metabolic-
acidosis#:~:text=Causes%20include%20accumulation%20of%20ketones,vomiting%2C%20lethargy%2C%20and%20hyperpnea.

14. General Management:
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Metabolic Acidosis (Cont’d)
UpToDate. (n.d.). Retrieved January 30, 2022, from https://www.uptodate.com/contents/approach-to-the-adult-with-metabolic-
acidosis?search=acid+base+disorders+management&amp;source=search_result&amp;selectedTitle=1~150&amp;usage_type=default&amp;display_rank=1#H17
Removal of offending agent
Supportive care
Correction of any electrolyte disturbances
If Ph < 7.15 → Infuse 2 ampules (100 mL) of 7.5 percent sodium
bicarbonate (44.6 mEq/50 mL) over 1 to 2 minutes

15. Alternative agent to bicarbonate:
• Tromethamine (tris-hydroxymethyl aminomethane; also called THAM, TRIS, and
trometamol) is an alternative to sodium bicarbonate. The manufacturer of THAM has not
continuously produced the drug, and therefore it is not always available. Although used
by some clinicians.
• Unlike bicarbonate, which generates carbon dioxide (CO2) when it reacts with hydrogen
ions (H+), THAM consumes carbon dioxide.
• In addition, unlike sodium bicarbonate, THAM is not a sodium salt and therefore does
not provide a sodium load.
• THAM has been used to treat severe acidemia due to sepsis, permissive hypercapnia,
diabetic ketoacidosis, RTA, gastroenteritis, and drug intoxications
• Because of its ability to decrease pCO2, THAM is an alternative to bicarbonate that may
be the preferred buffer in critically ill patients with mixed metabolic and respiratory
acidosis.
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Metabolic Acidosis (Cont’d)
General Management:
UpToDate. (n.d.). Retrieved January 30, 2022, from https://www.uptodate.com/contents/approach-to-the-adult-with-metabolic-
acidosis?search=acid+base+disorders+management&amp;source=search_result&amp;selectedTitle=1~150&amp;usage_type=default&amp;display_rank=1#H17

16. Metabolic Alkalosis
Pathophysiology
• Loop diuretic
• Thiazide diuretic
• Penicillin
• Aminoglycoside
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Drugs Induced
Kitterer, D., Schwab, M., Alscher, M. D., Braun, N., &amp; Latus, J. (2020, November 5). Drug-induced acid-base disorders . SpringerLink. Retrieved January 30,
2022, from https://link.springer.com/article/10.1007/s00467-014-2958-5
Distal H+ & Cl- excretion
Associated HCO3
reabsorption
Increased aldosterone synthesis
Increased K+ secretion
Increased urine Ca
excretion
Bartter like syndrome

17. Clinical Manifestation:
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Metabolic Alkalosis (Cont’d)
Respiratory depression
Hypoxemia
Vasoconstriction
Angina
Tachycardia
Tremor
Kitterer, D., Schwab, M., Alscher, M. D., Braun, N., &amp; Latus, J. (2020, November 5). Drug-induced acid-base disorders . SpringerLink. Retrieved January 30,
2022, from https://link.springer.com/article/10.1007/s00467-014-2958-5

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Metabolic Alkalosis (Cont’d)
General Management:
Incase of hypokalemia & edema → Potassium chloride (20 -80 mEq/day) ±
amiloride
If AKI/CKD → Dialysis with low bicarbonate bath concentration
Removal of offending agent
If addition of diuresis needed add acetazolamide (250 – 500 mg Qd/ BID)
Correction of any electrolyte disturbances
Isotonic saline
management of metabolic alkalosis. UpToDate. (2021). Retrieved January 31, 2022, from https://www.uptodate.com/contents/treatment-of-metabolic-
alkalosis?search=metabolic+alkalosis+treatment&amp;source=search_result&amp;selectedTitle=1~150&amp;usage_type=default&amp;display_rank=1#H1863594

19. Take Home Message
Drugs commonly used in critical ill patient are associated with
various type of iatrogenic toxicities.
The underlying comorbidities and the patient s critical illness
increase the risk of developing drug induced toxicities. But also
complicate the ability to diagnose and finding contributing factors.
Management of drug induced toxicities usually involves the
discontinuation of the suspected medications and if needed,
supportive therapy to treat underlying manifestation.
19
Nazer, L. H., Brown, A. R. T., & Awad, W. (2021, June). Iatrogenic Toxicities in the Intensive Care Unit. Define_me. Retrieved January 29, 2022, from
https://www.criticalcare.theclinics.com/article/S0749-0704(21)00019-1/fulltext

20. Related Article
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BN;, K. T. R. R. C. L. (n.d.). A mechanism for pentamidine-induced hyperkalemia: Inhibition of distal nephron sodium transport. Annals of internal medicine. Retrieved January 31, 2022,
from https://pubmed.ncbi.nlm.nih.gov/7992983/

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For further information don’t
hesitate to contact me by
Zeinab.nm1163@gmail.com