Acid-base disorders in the ICU

Also known as Metabolic acidosis · Metabolic alkalosis · Anion gap · Delta gap · Stewart approach · MUDPILES

Acid-base interpretation is fundamental to ICU practice. Use a disciplined 9-step algorithm: (1) pH (acidaemia/alkalaemia); (2) primary process (PaCO2 vs HCO3); (3) expected compensation (Winter formula); (4) A-a gradient; (5) anion gap (albumin-corrected); (6) delta gap; (7) osmolar gap; (8) lactate; (9) clinical correlation. High-AG acidosis = GOLDMARK (glycols, oxoproline, L- and D-lactate, methanol, aspirin, renal failure, ketoacidosis). Normal-AG = hyperchloraemic (diarrhoea, RTA, saline). Metabolic alkalosis: urine chloride separates saline-responsive from resistant. Chronic respiratory acidosis: classic rules have HCO3 rising 3.5 mmol/L per 10 mmHg; human COPD data suggest more. Treat the cause, not the number — BICAR-ICU found no overall benefit from sodium bicarbonate in severe acidaemia (pH at or under 7.20) with more hypernatraemia and metabolic alkalosis, though the AKI subgroup fared better.

high35 referencesUpdated 17 Aug 202620 min readSource-verified · Sept 2026

Checked against its sources on 2 Sept 2026

^[1] ^[2] ^[4]

Meet the patient

Mr K, 68, severe COPD on home BiPAP, is dragged in by his wife after three days of intractable vomiting from a small-bowel obstruction. He is febrile, RR 28, SpO2 88% on his usual 2 L/min, BP 96/60, lactate 3.2 mmol/L. The gas looks almost reassuring — pH 7.34, PaCO2 64 mmHg, HCO3 34 mmol/L, Cl 92, albumin 30 g/L. Hold that single near-normal pH in your head and run the arithmetic anyway: complex acid-base disorders coexist even when the pH appears normal. ^[25]

A near-normal pH never excludes a mixed disorder — two opposing processes can cancel at the hydrogen-ion level while both remain active. In this man it conceals a chronic respiratory acidosis, a vomiting-driven metabolic alkalosis, and a septic high-anion-gap acidosis all at the same time. Two questions and everything below slots into place: (a) is the compensation what the expected-response rules predict, and (b) does the delta gap agree with the anion gap? ^[25]^[1]

References35Show

[1]Morikawa MJ Acid-Base Interpretation: A Practical Approach Am Fam Physician, 2025.PMID 39964926
[2]Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management Nat Rev Nephrol, 2010.PMID 20308999
[3]Emmett M, Narins RG Clinical use of the anion gap Medicine (Baltimore), 1977.PMID 401925
[4]Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial Lancet, 2018.PMID 29910040
[5]Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults N Engl J Med, 2018.PMID 29485925
[6]Young P, Bailey M, Beasley R, et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial JAMA, 2015.PMID 26444692
[7]Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA, 2016.PMID 26903338
[8]Marano M Evaluation of the expected ventilatory response to metabolic acidosis in chronic hemodialysis patients Hemodial Int, 2018.PMID 28834137
[9]Figge J, Jabor A, Kazda A, Fencl V Anion gap and hypoalbuminemia Crit Care Med, 1998.PMID 9824071
[10]Wrenn K The delta (delta) gap: an approach to mixed acid-base disorders Ann Emerg Med, 1990.PMID 2240729
[11]Martinu T, Menzies D, Dial S Re-evaluation of acid-base prediction rules in patients with chronic respiratory acidosis Can Respir J, 2003.PMID 14530822
[12]Zubieta-Calleja G, Zubieta-Castillo G, Zubieta-Calleja L, et al. Do over 200 million healthy altitude residents really suffer from chronic Acid-base disorders? Indian J Clin Biochem, 2011.PMID 22211016
[13]Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial JAMA, 2010.PMID 20179283
[14]Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial Am J Respir Crit Care Med, 2010.PMID 20463176
[15]Dufel SE Urinary electrolytes Emerg Med Clin North Am, 1986.PMID 3512244
[16]Quintanilla AP Acute acid-base disorders. 2. Specific disturbances Postgrad Med, 1976.PMID 981088
[17]Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group N Engl J Med, 1999.PMID 10080845
[18]Mégarbane B Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole Open Access Emerg Med, 2010.PMID 27147840
[19]Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of methanol poisoning N Engl J Med, 2001.PMID 11172179
[20]Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup Ann Emerg Med, 2015.PMID 25986310
[21]Kraut JA, Xing SX Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis Am J Kidney Dis, 2011.PMID 21794966
[22]Alhourani HM, Kumar A, George LK, et al. Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen Am J Med Sci, 2018.PMID 29661353
[23]Kowlgi NG, Chhabra L D-lactic acidosis: an underrecognized complication of short bowel syndrome Gastroenterol Res Pract, 2015.PMID 25977687
[24]Kitterer D, Schwab M, Alscher MD, et al. Drug-induced acid-base disorders Pediatr Nephrol, 2015.PMID 25370778
[25]Habib T, Nair A, Murphy S, et al. Mastering blood gas interpretation: A practical guide for primary care providers S Afr Fam Pract, 2025.PMID 40336441
[26]Feldman M, Soni N, Dickson B Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap J Lab Clin Med, 2005.PMID 16310513
[27]Hantzidiamantis PJ, Amaro E Physiology, Alveolar to Arterial Oxygen Gradient StatPearls, 2026.PMID 31424737
[28]Tamzil R, Yaacob N, Noor NM, et al. Comparing the clinical effects of balanced electrolyte solutions versus normal saline in managing diabetic ketoacidosis: A systematic review and meta-analyses Turk J Emerg Med, 2023.PMID 37529790
[29]Peketi SH, Upadrista PK, Cadet B, et al. Salicylate Poisoning and Rebound Toxicity Cureus, 2024.PMID 38746490
[30]Zouboules SM, Lafave HC, O'Halloran KD, et al. Renal reactivity: acid-base compensation during incremental ascent to high altitude J Physiol, 2018.PMID 30267579
[31]Nazir S, Melnick S, Ansari S, et al. Mind the gap: a case of severe methanol intoxication BMJ Case Rep, 2016.PMID 26917798
[32]Fencl V, Jabor A, Kazda A, Figge J Diagnosis of metabolic acid-base disturbances in critically ill patients Am J Respir Crit Care Med, 2000.PMID 11112147
[33]Maeda A, Brown A, Spano S, et al. Furosemide with adjunctive acetazolamide vs furosemide only in critically ill patients: A pilot two-center randomized controlled trial J Crit Care, 2025.PMID 39689380
[34]Liu QS, Harji F, Jones A, et al. Type B lactic acidosis: a rare oncological emergency BMJ Case Rep, 2020.PMID 32234853
[35]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes Diabetes Care, 2009.PMID 19564476