Physiologic acid-base evaluation: Anion Gap and Delta-Delta calculations, Winter's formula for respiratory compensation, distinguishing ketoacidosis/lactic acidosis/toxic alcohols from non-gap acidosis, and bicarbonate therapy indications.
Acute metabolic acidosis (arterial pH < 7.35 with primary serum HCO3- < 22 mEq/L) is a hallmark of severe metabolic distress in the ICU. Severe acidemia (pH < 7.15–7.20) induces profound peripheral vasodilation, blunts myocardial responsiveness to catecholamines, impairs coagulation enzymes, and triggers life-threatening arrhythmias. Systematic physiologic evaluation requires calculating the Serum Anion Gap, assessing respiratory compensation via Winter's formula, and determining the Delta-Delta ratio.
Caution
Dangerous Diagnosis Not to Miss: Sepsis/Cardiogenic Shock with Type A Lactic Acidosis, Toxic Alcohol Ingestion (Methanol/Ethylene Glycol with high Osmolar Gap), Diabetic Ketoacidosis (including Euglycemic DKA from SGLT2 inhibitors), Acute Mesenteric Ischemia, and Severe Metformin-Associated Lactic Acidosis (MALA).
Formula: Serum Anion Gap = [Na+] - ([Cl-] + [HCO3-]). Normal AG is 8 to 12 mEq/L.
Albumin Correction: For every 1.0 g/dL drop in serum albumin below 4.0 g/dL, add 2.5 mEq/L to the calculated AG (Corrected AG = Observed AG + 2.5 × [4.0 - Albumin]). In critically ill hypoalbuminemic patients, an uncorrected 'normal' AG of 10 mEq/L frequently masks a dangerous high-anion-gap acidosis.
G — Glycols (Ethylene Glycol, Propylene Glycol from IV lorazepam/diazepam infusions).
O — Oxoproline (5-oxoproline / pyroglutamic acid from chronic high-dose acetaminophen ingestion).
L — L-Lactate: Type A (tissue hypoperfusion/shock, mesenteric ischemia, CPR, seizure) vs Type B (liver failure, metformin, propofol, beta-2 agonists [epinephrine/albuterol], linezolid, malignancy).
D — D-Lactate: Short bowel syndrome / small intestinal bacterial overgrowth.
M — Methanol: Windshield washer fluid ingestion (toxic metabolite formic acid causes optic disc edema / blindness).
A — Aspirin / Salicylates: Mixed respiratory alkalosis + high anion gap metabolic acidosis (tinnitus, tachypnea, hyperthermia).
R — Renal Failure: Uremic acidosis (retention of sulfates, phosphates, urates in advanced AKI/ESKD).
K — Ketoacidosis: Diabetic Ketoacidosis (DKA), Alcoholic Ketoacidosis (AKA), Starvation Ketoacidosis.
Massive Resuscitation with 0.9% Normal Saline (infusion of high chloride [154 mEq/L] expands extracellular volume, displacing bicarbonate; switch to balanced crystalloids [Plasma-Lyte / Lactated Ringer's]).
Gastrointestinal Bicarbonate Losses: Severe secretory diarrhea, enterocutaneous / pancreatic / biliary fistulas, ileostomy output.
Renal Tubular Acidosis (RTA): Type 1 (distal), Type 2 (proximal), Type 4 (hyporeninemic hypoaldosteronism with hyperkalemia).
Carbonic Anhydrase Inhibitors (Acetazolamide).
Caution
Common Diagnostic Trap: Administering IV Sodium Bicarbonate in a patient with severe hypoventilation or exhausted respiratory muscles without mechanical ventilatory support. Bicarbonate buffering generates immense amounts of carbon dioxide (CO2); if the lungs cannot blow off CO2, it rapidly diffuses into myocardial and brain cells, precipitating paradoxical worsening of intracellular acidosis.
Acid-Base Disorders: Detailed Henderson-Hasselbalch equations, Stewart physicochemical approach, and mixed disorder tables.
AKI: Uremic metabolic acidosis, FST, and renoprotection.
CRRT: Bicarbonate-buffered dialysate/replacement fluids and acid-base clearance.
Shock & Septic Shock: Lactate kinetics and tissue perfusion endpoints.
Hyperkalemia: Acidosis-induced extracellular potassium shifting.
Evidence status
Review metadata not yet recorded.
Status, review dates and guideline versions appear here once editorial metadata is authored for this content.
From recognizing hypoperfusion and initial crystalloid bolus to dynamic fluid responsiveness assessment and vasopressor targets.
From first-line norepinephrine titration to multi-agent vasopressor escalation and inotrope selection.
From multi-vasopressor failure to rescue non-adrenergic agents and mechanical circulatory support.
From confirming true hypotension to recognizing shock and its likely category.
Differential diagnosis (GOLD MARK vs HARDCARP), toxic alcohol osmolar gaps, Urine Anion Gap, and current sodium bicarbonate evidence including BICAR-ICU and BICARICU-2.
Stepwise 6-step interpretation algorithm, compensation formulas, albumin-corrected anion gap, delta ratio, and Stewart physicochemical (SID) principles.
Pathophysiology, SGLT2i euglycemic DKA, balanced fluid resuscitation, potassium-before-insulin safety rules, dextrose addition kinetics, and subcutaneous transition.
Resuscitate first, identify toxidromes and ECG/acid-base threats, use toxin-specific antidotes, and escalate early to poison-center, extracorporeal, or ECLS support when physiology demands it.
Sepsis-AKI microcirculatory decoupling, KDIGO staging, Furosemide Stress Test (FST), urine microscopy, and the AEIOU dialysis threshold framework.
Principles of convection vs diffusion, filtration fraction, delivered effluent dosing (20–25 mL/kg/h), Regional Citrate Anticoagulation, and citrate toxicity.
Cellular dysoxia, DO2/VO2 physiology, the 4 shock phenotypes, dynamic fluid responsiveness (PLR/PPV) vs fluid tolerance (VExUS), and vasoactive pharmacology.
The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.
Nernst resting potential mechanics, ECG progression, the 3-step resuscitation framework (Stabilize, Shift, Eliminate), and post-dialysis rebound kinetics.