›Nebulized albuterol 10 mg to 20 mg as an adjunct
›Evidence for potassium shift is modest and effect is short-lived, not a substitute for definitive therapy
›Definitive therapy is extracorporeal removal, which corrects both the acidemia and the hyperkalemia
›Role and controversy
›Evidence does not support routine bicarbonate to improve survival in severe lactic acidosis
›Concerns include paradoxical intracellular and cerebrospinal fluid acidosis from generated CO2, sodium and volume overload, and a leftward oxyhemoglobin dissociation shift
›Reasonable role as a temporizing bridge to definitive extracorporeal removal in profound acidemia, not as a substitute for it
›Sodium bicarbonate IV bolus
›1 mmol/kg IV
›Typical adult 50 mmol to 100 mmol
›Reserve for pH below 7.1 or hemodynamic instability attributable to acidemia
›Do not bolus if the patient is already volume overloaded or anuric, start the infusion at a slower rate instead
›Sodium bicarbonate infusion
›Mix 150 mmol sodium bicarbonate in 1 L D5W
›Infuse at 150 mL/hour to 250 mL/hour
›Slow to 50 mL/hour to 100 mL/hour once pH exceeds 7.2 rather than stopping abruptly
›Monitoring
›Blood gas and electrolytes every 1 to 2 hours during the infusion
›Ionized calcium and potassium can fall further with alkalinization, recheck with each gas
›Continuous ECG for QT and rhythm change during rapid electrolyte shift
›Cumulative dose limit
›Cap empiric bicarbonate at approximately 300 mmol in the first several hours pending dialysis, then reassess rather than continuing indefinitely
›An escalating bicarbonate requirement without pH improvement is a trigger to expedite dialysis, not to increase the infusion further
›Hemodialysis indications
›Severe acid-base failure
›pH 7.0 or lower
›Lactate 20 mmol/l or higher
›Shock
›Hemodynamic instability despite fluids and vasopressors
›Decreased level of consciousness
›Failure of standard supportive measures
›Persistent or worsening acidemia despite fluids, vasopressors, and the bicarbonate bridge over 1 to 2 hours
›Acute kidney injury
›KDIGO stage 3
›Markedly elevated metformin concentration when available, though rarely obtainable in time to guide acute treatment
›Modality selection
›Intermittent hemodialysis is preferred when hemodynamics permit
›Metformin is small, water-soluble, and minimally protein-bound, giving it high dialysance
›Higher blood and dialysate flow clears metformin and lactate faster than continuous therapy
›Continuous renal replacement therapy for hemodynamically unstable patients who cannot tolerate intermittent hemodialysis
›Slower clearance but better tolerated in shock
›Sustained low-efficiency dialysis as an intermediate option where available
›Rebound and prolonged or repeated therapy
›Extensive tissue redistribution of metformin causes rebound after a single dialysis session
›Repeat or extend dialysis, or transition to continuous therapy, until lactate and pH remain stable off treatment
›Recheck lactate and metformin concentration 2 to 4 hours after stopping dialysis
›Vascular access and anticoagulation
›Urgent dialysis catheter placement if no access is present
›Circuit anticoagulation
›Heparin per local protocol, weighed against bleeding risk from uremic platelet dysfunction or coexisting coagulopathy
›Citrate regional anticoagulation as an alternative, used with caution since citrate metabolism itself depends on adequate liver and renal function
›Intubation strategy when unavoidable
›Preserve compensatory hyperventilation as long as possible
›Avoid sedation or paralysis that abolishes the patient's own respiratory compensation before it is replaced by the ventilator
›Rapid sequence induction agent choice
›Ketamine 1 mg/kg to 2 mg/kg IV or etomidate 0.3 mg/kg IV, both reasonable given relative hemodynamic stability
›Avoid succinylcholine if hyperkalemia is present or suspected from concurrent acute kidney injury
›Rocuronium 1.2 mg/kg IV as the paralytic of choice in that setting
›Post-intubation ventilator targets
›Match or exceed the patient's pre-intubation minute ventilation
›Avoid normalizing PaCO2, permissive hypercapnia worsens acidemia further
›Immediate post-intubation blood gas to confirm adequate compensation is maintained
Precipitant-directed therapy
›Sepsis pathway
›Empiric broad-spectrum antibiotics per local sepsis protocol after cultures if a suspected infectious precipitant is present
›Source control as indicated
›Cardiac and hypoxic precipitants
›Treat concurrent myocardial infarction or decompensated heart failure per standard protocols
›Correct hypoxemia
›Nephrotoxin and contrast avoidance
›Discontinue NSAIDs, ACE inhibitors, and ARBs during the acute kidney injury
›Avoid further iodinated contrast unless clinically essential
›Mesenteric ischemia concern
›Surgical consultation if suspected on exam or imaging
›Does not exclude concurrent metformin accumulation, treat both
Metformin cessation and monitoring
›Immediate cessation
›Hold metformin on presentation regardless of the suspected mechanism
›No specific antidote exists for metformin, unlike fomepizole for the toxic alcohols
›Decontamination in acute large overdose
›Activated charcoal 1 g/kg PO or NG, adult typical 50 g, if within 1 to 2 hours of a large acute ingestion and the airway is protected
›Limited evidence of outcome benefit but low risk with a protected airway
›Ongoing monitoring
›Serial lactate and blood gas every 1 to 2 hours until trending toward normal
›Renal function trend to guide safe resumption
›Do not resume metformin until renal function and acid-base status have returned to baseline and the precipitant is resolved
Iatrogenic harms and troubleshooting
›Intubation and sedation
›Sedation and paralysis abolish compensatory hyperventilation
›An acute drop in pH and cardiovascular collapse can follow rapidly if ventilation does not match the metabolic demand
›Succinylcholine can precipitate cardiac arrest via exaggerated hyperkalemia in unrecognized acute kidney injury
›Use rocuronium instead when hyperkalemia is present or suspected
›Fluid loading
›Required to restore renal perfusion, but excess volume in oliguric renal failure precipitates pulmonary edema
›Chloride-rich fluid load causes hyperchloremic acidosis that obscures the anion gap trend used to track the lactic acidosis
›Oxygen
›Routine high-flow oxygen is appropriate for hypoxia or shock
›Avoid unnecessary hyperoxia once saturation targets are met
›Vasopressors
›No specific contraindication, generally appropriate and expected in shock
›Mechanical circulatory support
›Intra-aortic balloon pump has no established role unless concurrent cardiogenic shock is present
›Extracorporeal membrane oxygenation has been reported as a bridge to dialysis in refractory shock or arrest from severe cases, an extreme rescue option rather than routine therapy
›Anticoagulation
›Required for the dialysis circuit
›Weigh against bleeding risk from uremic platelet dysfunction or coexisting coagulopathy
›Fibrinolysis
›No specific pharmacologic interaction with metformin lactic acidosis
›Standard indications and contraindications apply
›Do not let fibrinolytic decision-making delay arranging definitive extracorporeal removal
›Analgesia
›Opioid metabolites accumulate in acute kidney injury and can further blunt compensatory hyperventilation
›Fentanyl is preferred over morphine given minimal active renally cleared metabolites
›NSAIDs are contraindicated
›They worsen the renal injury that is often the precipitant
›ECG interpretation during electrolyte shift
›Hyperkalemia from concurrent acute kidney injury
›Peaked T waves
›Widened QRS progressing toward a sine wave pattern
›Overcorrection during bicarbonate therapy or after dialysis
›Hypokalemia with flattened T waves and U waves
›Hypocalcemia with QT prolongation
›Therapy not working
›Lactate not improving despite adequate dialysis
›Consider inadequate dialysis dose or vascular access recirculation
›Consider ongoing absorption from a sustained-release formulation, bezoar, or ileus
›Reconsider an unrecognized type A cause such as bowel ischemia or occult shock