#antidotes See [goldfrank sodium bicarbonate](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=593), [Marino - alkali therapy](x-devonthink-item://E1BD9A1B-B9D6-4AEA-8B93-01670E2EAA15?page=577) Interesting case: [TCA OD and HCO3 OD](https://www5.austlii.edu.au/au/cases/act/ACTCD/2025/1.html): pt got 1.6 L of HCO3 (16 bottles) titrating to QRS and developed critical metabolic alkalosis, hypernatraemia, and cerebral oedema. [EMA 2022 - Too much of a good thing: Bicarbonate toxicity following treatment of sodium channel blocker overdose.](bookends://sonnysoftware.com/ref/DL/240327) - [online link](https://onlinelibrary.wiley.com/doi/10.1111/1742-6723.13995) > [!key points] Key Points about giving HCO3 therapy to treat overdose > - ventilation is important when giving bicarbonate therapy. HCO3 may paradoxically worsen the pH with ↑ pCO2. gently hyperventilate, aiming for low-normal pCO2 in most cases (pCO2 30-35 if TCA) > - the QRS often remains prolonged eg 120-140ms for 24-48 hours following severe TCA overdose, so do not aim for an unrealistic QRS target (eg 100-120) ms because this probably will never happen. > - furthermore, in [[Sodium channel blocker|sodium channel blocker toxicity]] due to non-TCA medications, the QRS prolongation *may not respond to HCO3* at all > - also, avoid treating a broad complex QRS that is not secondary to Na-channel toxicity but is actually pre-existing interventicular conduciton delay > - perform [[Blood gas]] analysis regularly to ensure target pH and pCO2 are met and iatrogenic harm is avoided. severe [[hypokalemia|hypo-k]] can be easy to miss # indications - poisoning - [[TCA overdose]], other [[Sodium channel blocker|sodium channel blocker toxicity]] - [[toxic alcohols]] - [[Cyanide]] - [[Aspirin overdose|Salicylates]] - [[Cardiac arrest]] -- improve contractility, consideration as treatment for [[hyperkalemia]] - Renal tubular acidosis - [[rhabdomyolysis]] # Overview 8.4% NaHCO3 contains 1mmol/mL of Na and 1mmol/mL of HCO3 NOTE this is twice the Na of 3% saline, which contains about 0.51mmol/mL of Na # hazards of HCO3 therapy - high solute load - can quickly lead to [[hypernatremia]] - [[hypokalemia]] - [[Hypocalcemia]] - Cerebral oedema from salt load - ↑ Na → water drawn out of cells by osmosis → cell shrinkage → treatment → cells swell → ↑ ICP → ischaemia and brain damage/death - Hyperosmolarity - May worsen CSF acidosis, especially if pH > 6.9 - Need to hyperventilate to blow off added CO2 - can precipitate hepatic encephalopathy - in children younger than 2 years of age, the 4.2% solution is preferred in these patients. - Extravasation causes local tissue damage. - Dobutamine and norepinephrine are incompatible with sodium bicarbonate solutions, and calcium solutions cause precipitation. # Mechanism of action **For TCA and other Na-channel blockers:** - ↑ \[Na+] - a change in the proportion of the Na+ channel blocker that is ionized, resulting in an altered distribution away from its channel - Because TCAs are weakly basic, they are increasingly ionized as the ambient pH falls and less ionized as the pH rises. Changing the ambient pH therefore alters their binding to the sodium channel. This probably occurs because 90% of the binding of CA to the sodium channel occurs in the ionized state, alkalinizing the blood facilitates the movement of the CA away from the hydrophilic sodium channel and into the lipid membrane **For aspirin toxicity** - alter distribution and enhance elimination **For toxic alcohols** - correct life threatening acidosis # Dosing ## TCA overdose - 8.4% HCO3 1-2mmol/kg (100mL is a vial) Q2-4 min aim pH 7.5-7.55 - max total dose 6mL/kg; if no response d/w toxicologist - also need to hyperventilate patient as well aim pCO2 30-35 - expect narrowing but not normalisation of the QRS interval ## Non-TCA poisoning e.g. [[lamotrigine overdose]], flecainide, and [[beta blocker overdose|propranolol]] : all cause [[Sodium channel blocker|sodium channel blocker toxicity]] - Give 1mmol/kg or 100mL bolus Q 3-5 min PRN to max dose of 3 mmol/kg and gentle hyperventilate until normal pH target of 7.35-7.45 reached on ABG # other buffering agents Carbicarb - less co2 than hco3 Dichloroacetate - increase pyruvate dehydrogenase activity --> increasw conversion to acetyl coa --> increase metabolism of lactate back to pyruvate - Acts as an [[ionodilator]] - Theoretical benefits; has not been shown to alter outcomes Tham - used in scandinavia, available in USA - contains tromethamine (proton acceptor. Generates NH3/HCO3 without producing CO2, avoids Na+ load) - Rapid ECF and slow ICF distribution - PKA 7.8, therefore more effective atu usual ph range than hco3 - Can cause resp depression, hypoglycemia Tribonat - also used mostly in scandanavia - THAM, NaHCO3, acetate, phosphate - 1/3 Na content of HCO3, so less increase in serum osmolality - Lower risk of ph over-correction because buffering capacity diminished above ph 7.4 - Adverse: resp depression, hypoglycemia, frees Ca2C --> peripheral vasodilation (may divert blood away from core during CPR)