Present in neonates and infants with unexplained HAGMA
Urine organic acids and plasma amino acids for diagnosis
Inborn errors of metabolism
Maple syrup urine disease, fatty acid oxidation defects
Family history and neonatal screening context important
Pediatric DKA treatment
Fluid resuscitation caution
Excessive fluid linked to cerebral edema in pediatric DKA
ISPAD guidelines: 10 mL/kg bolus only for hemodynamic compromise
Replace deficit over 24 to 48 hours at maintenance rate
Insulin infusion
0.05 to 0.1 units/kg/hour (lower than adult dosing)
Start after 1 hour of IV fluids if no hypokalemia
Potassium repletion
40 mmol/L added to IV fluids when K <5.5 mmol/l and urinating
Higher supplementation needs than adults relative to body weight
Weight-based dosing
Sodium bicarbonate for cardiac arrest
1 to 2 mmol/kg IV in neonates and children
Use 4.2% solution in neonates to avoid hyperosmolar injury
Fomepizole for toxic alcohol
Same mg/kg dosing as adults
Loading dose 15 mg/kg IV over 30 minutes
Cerebral edema management in pediatric DKA
3% hypertonic saline 2.5 to 5 mL/kg IV over 10 minutes if cerebral edema suspected
Mannitol 0.5 to 1 g/kg IV alternative
Background
Epidemiology
Prevalence and incidence
Metabolic acidosis in critically ill patients
Present in up to 64% of ICU patients
Lactic acidosis is the most common cause, accounting for approximately 50% of HAGMA
DKA epidemiology
Incidence rising, estimated 145,000 hospitalizations per year in the US
Mortality rate approximately 1% overall but higher with cerebral edema (pediatric)
CKD-related chronic metabolic acidosis
Affects 10% to 20% of patients with CKD stage 3 to 4
Prevalence increases with declining GFR
Outcomes and mortality
Lactic acidosis from sepsis
Lactate >4 mmol/l associated with mortality exceeding 40%
Lactate elevation reflects disease severity more than independent cause of death
Toxic alcohol ingestion
Untreated methanol: mortality >20%, blindness in survivors
Ethylene glycol untreated: acute renal failure and death within days
Severe metabolic acidosis (pH <7.20)
Associated with significantly increased mortality regardless of etiology
AKI concurrent with severe acidemia increases mortality further
Pathophysiology
Mechanisms of acid-base disturbance
Proton excess or bicarbonate loss
Net acid production exceeds renal excretory capacity
Bicarbonate titrated as buffer
Bicarbonate lost directly from GI or renal tract
Respiratory compensation
Carotid body chemoreceptor detection of pH fall
Hyperventilation increases CO2 elimination
Cannot fully compensate; pH remains below normal
HAGMA mechanisms by category
Lactic acidosis
Type A: tissue hypoperfusion and anaerobic metabolism
Type B: impaired lactate clearance (liver failure, metformin, thiamine deficiency)
Pyruvate to lactate ratio shift
Ketoacidosis
Insulin deficiency allows unopposed lipolysis
Free fatty acid conversion to acetoacetate and beta-hydroxybutyrate
Both are strong organic acids consumed by buffering bicarbonate
Toxic alcohol metabolism
Methanol metabolized to formate via formaldehyde (alcohol dehydrogenase)
Formate causes optic nerve toxicity and mitochondrial dysfunction
Ethylene glycol metabolized to glycolate, oxalate; oxalate deposits cause AKI
NAGMA mechanisms
GI bicarbonate loss
Pancreatic, intestinal, and biliary secretions rich in HCO3
Diarrhea causes direct loss without matched chloride retention
Renal tubular acidosis
Distal (Type 1): failure to secrete H into collecting duct
Proximal (Type 2): failure to reabsorb filtered HCO3
Type 4: hypoaldosteronism impairing K and H excretion
Cardiovascular effects of severe acidemia
Contractility impairment at pH <7.20
Reduced calcium sensitivity of myofibrils
Sympathetic activation partially counteracts
Arrhythmia risk from acidemia and hyperkalemia combination
ECG changes preceding lethal arrhythmia
Therapeutic Considerations
Treat the underlying cause first
Bicarbonate therapy is adjunctive, not definitive
Antibiotics and source control in sepsis
Insulin and fluids in DKA
Fomepizole in toxic alcohol
Dialysis removal in salicylate or toxic alcohol with renal failure
Overfocus on pH number without etiology treatment leads to recurrence
Bicarbonate therapy evidence base
BICARICU-2 (JAMA 2025): IV bicarbonate reduced RRT need in pH <=7.20 plus moderate-to-severe AKI
Included 389 patients across 15 ICUs in France
Primary endpoint of death or RRT at 28 days reduced
Routine bicarbonate in lactic acidosis without AKI not supported
CO2 generation worsens intracellular acidosis
Volume overload and hypernatremia risks
Balanced crystalloid advantage
Normal saline causes hyperchloremic NAGMA
Every 1 L normal saline adds 154 mmol chloride
Particularly relevant in large-volume DKA or sepsis resuscitation
Lactated Ringer and Plasmalyte avoid iatrogenic acidosis
Clinical outcomes data supporting balanced crystalloids in ICU (SMART trial)
Hemodialysis as therapeutic option
Clears toxic alcohols, salicylates, and uremic acids
Corrects severe electrolyte abnormalities concurrent with acidosis
Continuous RRT preferred when hemodynamically unstable
Intermittent HD for hemodynamically stable patients with toxic alcohol
EXTRIP guidelines define specific thresholds for each toxin
Patient Discharge Instructions
copy discharge instructions
Metabolic acidosis home care
Take all prescribed medications exactly as directed
Continue oral sodium bicarbonate or sodium citrate if prescribed
Avoid medications that were identified as causing or worsening acidosis until physician review
Adequate hydration daily (6 to 8 glasses of water unless fluid restricted)
DKA sick-day rules
Never stop insulin during illness even if not eating
Check blood glucose every 2 to 4 hours when unwell
Check urine or blood ketones with high glucose readings
Call diabetes care team early with illness
CKD-related acidosis instructions
Medication adherence with sodium bicarbonate is important for kidney protection
Follow kidney-friendly diet: reduce animal protein, increase fruits and vegetables
Avoid nephrotoxic medications (NSAIDs, certain antibiotics)
Keep all nephrology follow-up appointments
Warning signs to return to ER
Persistent vomiting or inability to keep liquids down
Confusion, extreme drowsiness, or difficulty waking
Fruity or unusual breath odor returning
Rapid or very deep breathing at rest
Visual changes, blurring, or loss of vision
Seizure or loss of consciousness
Severe abdominal pain
Decreased urine output or no urination for more than 8 hours
Palpitations or chest pain
Follow-up
Return to emergency department or urgent care in 24 to 48 hours if discharged with mild acidosis
Nephrology or primary care in 1 to 2 weeks for CKD-related acidosis adjustment
Diabetes team within 48 to 72 hours after DKA episode
Psychiatry or crisis services if acidosis related to intentional ingestion
References
Guidelines and key sources
Primary clinical references
Morikawa MJ, Ganesh PR. Acid-Base Interpretation: A Practical Approach. American Family Physician. 2025
Achanti A, Szerlip HM. Acid-Base Disorders in the Critically Ill Patient. CJASN. 2023
Berend K, de Vries AP, Gans RO. Physiological Approach to Assessment of Acid-Base Disturbances. NEJM. 2014
Jung B et al. Sodium Bicarbonate for Severe Metabolic Acidemia and Acute Kidney Injury (BICARICU-2). JAMA. 2025
Toxicology references
Kraut JA, Mullins ME. Toxic Alcohols. NEJM. 2018
Ghannoum M et al. Extracorporeal Treatment for Ethylene Glycol Poisoning: EXTRIP Workgroup. Critical Care. 2023
Roberts DM et al. Extracorporeal Treatment for Methanol Poisoning: EXTRIP Workgroup. Critical Care Medicine. 2015
Inman B et al. High Risk and Low Prevalence Diseases: Toxic Alcohol Ingestion. Am J Emerg Med. 2023
CKD and chronic acidosis references
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD. Kidney International. 2024
Navaneethan SD et al. KDOQI Commentary on KDIGO 2024 CKD Guideline. Am J Kidney Dis. 2025
Mahboobi S et al. Dietary Interventions for Metabolic Acidosis in CKD. NDT. 2025
Wesson DE et al. Veverimer vs Placebo in CKD-related Metabolic Acidosis. Lancet. 2019
DKA and electrolyte references
Veauthier B, Levy-Grau B. Diabetic Ketoacidosis: Evaluation and Treatment. American Family Physician. 2024
Kim MJ, Valerio C, Knobloch GK. Potassium Disorders. American Family Physician. 2023
Aamir N, Ralto KM. Treatment of Acute Metabolic Acidosis. Curr Opin Nephrol Hypertens. 2025
Coding and classification
ICD-10 E87.2 Acidosis; lactic acidosis
ICD-10 E10.10 Type 1 diabetes with ketoacidosis without coma
ICD-10 T52.8 Toxic effects of other organic solvents (glycols)
ICD-10 N18.6 End stage renal disease
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.