HAART-induced lactic acidosis: Difference between revisions
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==Background== | ==Background== | ||
*Nucleoside Reverse Transcriptase Inhibitors are associated with hyperlactemia and lactic acidosis | *Nucleoside Reverse Transcriptase Inhibitors are associated with hyperlactemia and lactic acidosis | ||
**NRTI also cause pancreatitis, myopathy, peripheral neuropathy, anemia, neutropenia, hepatic toxicity<ref> Lee WM, Dienstag JL. Lee W.M., Dienstag J.L. Lee, William M., and Jules L. Dienstag.Toxic and Drug-Induced Hepatitis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J Eds. Dennis Kasper, et al.eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130§ionid=79748661. Accessed August 22, 2017.</ref> | |||
**Specifically didanosine (ddI) and stavudine (d4T) | **Specifically didanosine (ddI) and stavudine (d4T) | ||
**These medicines are no longer first-line agents in the US and Europe, but are in low-middle income countries | **These medicines are no longer first-line agents in the US and Europe, but are in low-middle income countries | ||
*Adverse effects of NRTI is by way of mitochondrial toxicity. | *Adverse effects of NRTI is by way of mitochondrial toxicity. | ||
**NRTI inhibit human DNA polymerase gamma, a key enzyme for mitochondrial replication. | **NRTI inhibit human DNA polymerase gamma, a key enzyme for mitochondrial replication. | ||
**Impaired electron transport chain, leading to leakage of electrons and increased production of reactive oxygen species.<ref>Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. Review. PubMed PMID: 23963694; PubMed Central PMCID: PMC3951641.</ref> | **Impaired electron transport chain, leading to leakage of electrons and increased production of reactive oxygen species.<ref name="Margolis">Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. Review. PubMed PMID: 23963694; PubMed Central PMCID: PMC3951641.</ref> | ||
**Variable onset of mitochondrial toxicity, and not at any set point in NRTI use. <ref | **Variable onset of mitochondrial toxicity, and not at any set point in NRTI use. <ref name="Margolis" /> | ||
==Clinical Features== | ==Clinical Features== | ||
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*Tachypnea, dyspnea | *Tachypnea, dyspnea | ||
*Renal abnormalities | *Renal abnormalities | ||
*Since the symptoms are non-specific, most patients present with advanced symptoms and the more serious lactic acidosis. <ref>Dragovic G, Jevtovic D. The role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients. Biomed Pharmacother. 2012 Jun;66(4):308-11. doi: 10.1016/j.biopha.2011.09.016. Epub 2012 May 15. PubMed PMID: 22658063.</ref> | *Since the symptoms are non-specific, most patients present with advanced symptoms and the more serious lactic acidosis. <ref name="Dragovic">Dragovic G, Jevtovic D. The role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients. Biomed Pharmacother. 2012 Jun;66(4):308-11. doi: 10.1016/j.biopha.2011.09.016. Epub 2012 May 15. PubMed PMID: 22658063.</ref> | ||
==Risk Factors== | ==Risk Factors== | ||
*Use of stavudine and didanosine containing regimens | *Use of stavudine and didanosine containing regimens | ||
*CD4 count <200 <ref | *CD4 count <200 <ref name="Dragovic" /> | ||
**Additional studies cite a CD4 count less than 500 as a risk factor.<ref>Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.</ref> | **Additional studies cite a CD4 count less than 500 as a risk factor.<ref>Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.</ref> | ||
*Female 2.5x male<ref | *Female 2.5x male<ref name="Dragovic" /> | ||
*Plasma Triglycerides >2.2mmol/L | *Plasma Triglycerides >2.2mmol/L | ||
*Age, as the risk of hyperlactemia increases 50% with every 10 years of aging | *Age, as the risk of hyperlactemia increases 50% with every 10 years of aging | ||
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**Associated with dyslipidemia and insulin resistance<ref> Lewis W, Currie PF. HIV/AIDS AND THE CARDIOVASCULAR SYSTEM. In: Fuster V, Harrington RA, Narula J, Eapen ZJ. eds. Hurst's The Heart, 14e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=2046§ionid=155644091. Accessed August 22, 2017.</ref> | **Associated with dyslipidemia and insulin resistance<ref> Lewis W, Currie PF. HIV/AIDS AND THE CARDIOVASCULAR SYSTEM. In: Fuster V, Harrington RA, Narula J, Eapen ZJ. eds. Hurst's The Heart, 14e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=2046§ionid=155644091. Accessed August 22, 2017.</ref> | ||
== | ==Differential Diagnosis== | ||
*Sepsis | *Sepsis | ||
*Ischemia | *Ischemia | ||
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==Management== | ==Management== | ||
===Emergent=== | ===Emergent=== | ||
*Sodium bicarb (judicious doses<ref> Woo OF. Woo O.F. Woo, Olga F.Chapter 23. Antiviral and Antiretroviral Agents. In: Olson KR. Olson K.R. Ed. Kent R. Olson.eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=391§ionid=42069837. Accessed August 22, 2017.</ref>) | *Sodium bicarb (judicious doses<ref name="Woo"> Woo OF. Woo O.F. Woo, Olga F.Chapter 23. Antiviral and Antiretroviral Agents. In: Olson KR. Olson K.R. Ed. Kent R. Olson.eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=391§ionid=42069837. Accessed August 22, 2017.</ref>) | ||
*Cessation of offending drug | *Cessation of offending drug | ||
*Normal saline | *Normal saline | ||
*Anecdotal evidence to support Riboflavin (50mg/day), and/or thiamine (100mg BID) <ref | *Anecdotal evidence to support Riboflavin (50mg/day), and/or thiamine (100mg BID) <ref name="Woo" /> | ||
*Stop all anti-retrovirals until lactate normalization. .<ref | *Stop all anti-retrovirals until lactate normalization. .<ref name="Margolis" /> | ||
===Non Emergent=== | ===Non Emergent=== | ||
*Consider antioixidant supplementation to reduce oxidative stress and hyperlactemia<ref> Lopez O, Bonnefont-Rousselot D, Edeas M, Emerit J, Bricaire F. Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia? Biomed Pharmacother. 2003 May-Jun;57(3-4):113-6. PubMed PMID:12818471.</ref> | *Consider antioixidant supplementation to reduce oxidative stress and hyperlactemia<ref> Lopez O, Bonnefont-Rousselot D, Edeas M, Emerit J, Bricaire F. Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia? Biomed Pharmacother. 2003 May-Jun;57(3-4):113-6. PubMed PMID:12818471.</ref> | ||
==Disposition== | ==Disposition== | ||
==See Also== | ==See Also== | ||
==References== | ==References== | ||
<references/> | <references/> | ||
[[Category:ID]] | |||
Revision as of 04:06, 26 August 2017
Background
- Nucleoside Reverse Transcriptase Inhibitors are associated with hyperlactemia and lactic acidosis
- NRTI also cause pancreatitis, myopathy, peripheral neuropathy, anemia, neutropenia, hepatic toxicity[1]
- Specifically didanosine (ddI) and stavudine (d4T)
- These medicines are no longer first-line agents in the US and Europe, but are in low-middle income countries
- Adverse effects of NRTI is by way of mitochondrial toxicity.
Clinical Features
- Fatigue, malaise
- Nausea and or vomiting
- Unexplained mental status changes
- Neurologic Deficits, seizures
- Dysrhythmias
- Heart failure
- Weight gain/weight loss
- Tachypnea, dyspnea
- Renal abnormalities
- Since the symptoms are non-specific, most patients present with advanced symptoms and the more serious lactic acidosis. [3]
Risk Factors
- Use of stavudine and didanosine containing regimens
- CD4 count <200 [3]
- Additional studies cite a CD4 count less than 500 as a risk factor.[4]
- Female 2.5x male[3]
- Plasma Triglycerides >2.2mmol/L
- Age, as the risk of hyperlactemia increases 50% with every 10 years of aging
- Lipodystrophy and lipoatrophy
- Associated with dyslipidemia and insulin resistance[5]
Differential Diagnosis
- Sepsis
- Ischemia
Evaluation
- Creatinine clearance, as renal failure is a significant risk factor for the development of lactic acidosis from hyperlactemia. .[6]
- CBC
- Liver Function Test, as hepatic dysfunction precludes oxidation of lactate, thus resulting in elevated lactate levels in the blood
- Electrolytes
- Urinalysis
- Lactic Acid level
- ABG
- Lipase
- CPK
Management
Emergent
- Sodium bicarb (judicious doses[7])
- Cessation of offending drug
- Normal saline
- Anecdotal evidence to support Riboflavin (50mg/day), and/or thiamine (100mg BID) [7]
- Stop all anti-retrovirals until lactate normalization. .[2]
Non Emergent
- Consider antioixidant supplementation to reduce oxidative stress and hyperlactemia[8]
Disposition
See Also
References
- ↑ Lee WM, Dienstag JL. Lee W.M., Dienstag J.L. Lee, William M., and Jules L. Dienstag.Toxic and Drug-Induced Hepatitis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J Eds. Dennis Kasper, et al.eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130§ionid=79748661. Accessed August 22, 2017.
- ↑ 2.0 2.1 2.2 Margolis AM, Heverling H, Pham PA, Stolbach A. A review of the toxicity of HIV medications. J Med Toxicol. 2014 Mar;10(1):26-39. doi: 10.1007/s13181-013-0325-8. Review. PubMed PMID: 23963694; PubMed Central PMCID: PMC3951641.
- ↑ 3.0 3.1 3.2 Dragovic G, Jevtovic D. The role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients. Biomed Pharmacother. 2012 Jun;66(4):308-11. doi: 10.1016/j.biopha.2011.09.016. Epub 2012 May 15. PubMed PMID: 22658063.
- ↑ Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.
- ↑ Lewis W, Currie PF. HIV/AIDS AND THE CARDIOVASCULAR SYSTEM. In: Fuster V, Harrington RA, Narula J, Eapen ZJ. eds. Hurst's The Heart, 14e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=2046§ionid=155644091. Accessed August 22, 2017.
- ↑ Bonnet F, Balestre E, Bernardin E, Pellegrin JL, Neau D, Dabis F; Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. Risk factors for hyperlactataemia in HIV-infected patients, Aquitaine Cohort, 1999--2003. Antivir Chem Chemother. 2005;16(1):63-7. PubMed PMID: 15739622.
- ↑ 7.0 7.1 Woo OF. Woo O.F. Woo, Olga F.Chapter 23. Antiviral and Antiretroviral Agents. In: Olson KR. Olson K.R. Ed. Kent R. Olson.eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=391§ionid=42069837. Accessed August 22, 2017.
- ↑ Lopez O, Bonnefont-Rousselot D, Edeas M, Emerit J, Bricaire F. Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia? Biomed Pharmacother. 2003 May-Jun;57(3-4):113-6. PubMed PMID:12818471.