Thread by @Elena_Cervants

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🚨Is sodium bicarbonate useful to prevent Rhabdomyolysis induced AKI ❓❓🚨

We get asked this all the time! But in order to understand it, let's start with a simple question

What is the mechanism of AKI in rhabdomyolysis ❓❓

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1⃣What happens in rhabdo?
⚡️Muscle necrosis → release of intracellular components (enzymes-CK, electrolytes & myoglobin)
⚡️Fluid sequestration within damaged muscle → volume depletion →🚨 RAAS➕SNS
⚡️Oxidative injury →⬆️ in vascular mediators → ⬇️renal blood flow

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We might see ⬆️Creatine Kinase (CK) levels somewhat frequently...

BUT...

Is there a CK level that predicts AKI❓
⚡️There is no defined threshold value of CK
⚡️CK levels < 15,000 to 20,000 U/ L on admission usually have a low risk of AKI

pubmed.ncbi.nlm.nih.gov/16490621/

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More on pathophys...
2⃣What is MYOGLOBIN?
⚡️17.8 kDa protein
⚡️Enters tubular epithelial cells through endocytosis
⚡️⬆️Reactive Oxygen Species (ROS) and free radicals
⚡️Precipitates with the Tamm-Horsfall protein (THP) in the distal tubular lumen
pubmed.ncbi.nlm.nih.gov/19571284/

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The pathophysiology of AKI involves
⚡️Renal Vasoconstriction
⚡️Myoglobin induced oxidative injury
⚡️Intratubular cast obstruction

🚨Myoglobin induced direct cytotoxicity AND the formation of pigmented granular casts are favored by an ACIDIC URINE!! 🚨

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Before we dive into prevention 🚫 & treatment 💊 of AKI

🧪Beware of electrolyte complications...
- There is a ⬆️in serum K, Phos, Mg, uric acid
- There is a ⬇️in serum bicarbonate & Ca (initially⬇️then⬆️)

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The main strategy for 🚫prevention of AKI is:

💧IV volume repletion → target UO of 200-300 cc/hr
💧No difference between IVF solutions

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What other strategies would you use to prevent AKI?

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The role of bicarbonate for prevention of pigment nephropathy is perhaps one of the most common questions we get asked as nephrologists...

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Based on the mechanisms of AKi, alkalinizing the urine would prevent:
⚡️Precipitation of myoglobin -THP complexes → ⬇️intratubular cast formation
⚡️Reduction-oxidation cycling of myoglobin ---> ⬇️tubular injury
⚡️Metmyoglobin formation (vasoconstrictor) → ⬇️vasoconstriction

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So why don’t we give bicarbonate to everyone❓❓

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It turns out that alkalemia has been associated with higher mortality ☠️

pubmed.ncbi.nlm.nih.gov/3589765/

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Some of the downsides of alkalemia include:
🚫Depression of respiratory center
🚫Low iCa
🚫Low Myocardial Contractility
🚫Low Cerebral Blood Flow

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Since alkalemia is detrimental. Is there any evidence behind urine alkalinization❓

An animal model from 1952 by Perri GC and Gorini P showed that animals on an acidifying diet had a urine pH < 6 and developed AKI due to myoglobin precipitation

europepmc.org/backend/ptpmcr…

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In 1984, findings from animal models were reproduced in humans by Ron et.al
⚡️Urine alkalinization (target urine pH > 6.5) was used to treat 7 patients with rhabdomyolysis
⚡️None of them developed AKI by day 5
🚨 No control group
pubmed.ncbi.nlm.nih.gov/6696564/

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Different studies compared preventive & therapeutic regimens:
⚡️Early initiation of therapy with volume repletion is better
⚡️No difference between NS 🆚 NS +bicarb+mannitol
⚡️No difference between LR 🆚NS.
Both got bicarb if urine pH < 6.5. NS group required more bicarb

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SUMMARY:
⚡️AKI d/t rhabdo can be d/t vasoconstriction, oxidative injury & intratubular casts
⚡️Acidic urine ⬆️myoglobin toxicity in the proximal tubule AND precipitation of myoglobin-THP casts
⚡️CK levels < 15,000 to 20,000 U/ L on admission usually have a low risk of AKI

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SUMMARY:
⚡️Beware of electrolyte abnormalities!!
⚡️Aggressive IVF repletion is the 🗝️
⚡️A urine pH > 6.5 has been suggested to decrease the risk of AKI (limited data)
pubmed.ncbi.nlm.nih.gov/19571284/

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I hope you enjoyed this overview on the prevention of AKI in rhabdomyolysis 🤓

Special thanks to @NSMCinternship, #GroupofHenle @amyaimei @Nephro_Sparks @docanjuyadav @drM_sudha @jamiekwillows