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Metabolic AcidosisMANAGEMENT

ENDOCRINE AND METABOLIC PRESENTATIONS · 12 SECTIONS

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756 items

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Cardiovascular Presentations71▾

Respiratory Presentations52▾

Neurological Presentations83▾

Gastrointestinal Presentations74▾

Genitourinary and Reproductive Presentations48▾

Infectious Disease Presentations148▾

Trauma Presentations89▾

Toxicologic Presentations80▾

Psychiatric Presentations26▾

Musculoskeletal and Rheumatologic Presentations96▾

Dermatology Presentations23▾

Environmental and Exposure Presentations27▾

Hematologic and Oncologic Presentations36▾

Pediatric-Specific Presentations19▾

Endocrine and Metabolic Presentations45▾

Acute Porphyria Adrenal crisis Adrenal Insufficiency (Addisonian Crisis)Dehydration Diabetes Insipidus Diabetic Ketoacidosis (DKA)Euglycemic DKA (SGLT2 inhibitor)Galactosemia GLP-1 receptor agonist complications (retained gastric contents, aspiration risk)Homocystinuria Hypercalcemia Hyperkalemia Hypermagnesemia Hypernatremia Hyperosmolar Hyperglycemic State (HHS)Hypertensive emergency Hypertensive urgency Hypocalcemia Hypoglycemia Hypogonadism (Acute Presentation)Hypokalemia Hypomagnesemia Hyponatremia Hypoparathyroidism (Tetany)Insulin pump failure Maple Syrup Urine Disease (Crisis)Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)Metabolic Acidosis Metabolic Alkalosis Myasthenia gravis crisis Myxedema coma Pellagra Pheochromocytoma (Crisis)Pituitary Apoplexy Pompe Disease (GSD II)Respiratory Acidosis Respiratory Alkalosis Scurvy SIADH Starvation Ketosis Tarui Disease (GSD VII)Thyroid storm Tyrosinemia Vitamin D Deficiency (Severe-Rickets)Von Gierke Disease (GSD I)

ENT and Maxillofacial Presentations27▾

Ophthalmologic Presentations19▾

Obstetric Presentations23▾

Systemic and Miscellaneous Presentations17▾

01Approach to the Critical Patient/attcp44

Immediate priorities

›Airway and breathing threats

›Kussmaul respirations with fatigue

›Deep labored breathing as compensatory mechanism

›Fatigue risk at pH <7.10 as diaphragmatic dysfunction worsens

›Respiratory failure indicators

›Rising pCO2 despite tachypnea

›SpO2 declining

›If respiratory failure imminent, early intubation planning

›Avoid post-intubation apnea without matching pre-intubation minute ventilation

›Target ventilation rate to maintain pCO2 near pre-intubation level

›Hemodynamic threats

›Shock physiology

›SBP <90 mmHg

›MAP <65 mmHg

›Severe acidemia cardiovascular effects

›Impaired myocardial contractility at pH <7.20

›Peripheral vasodilation and vascular resistance loss

›Arrhythmia risk compounded by hyperkalemia

›Immediate IV access and fluid resuscitation with balanced crystalloids

›Prefer lactated Ringer over normal saline to avoid iatrogenic hyperchloremic acidosis

›Reassess after 1 to 2 L bolus

Key decision points

›Anion gap classification

›Calculate anion gap: Na minus (Cl plus HCO3); normal 12 plus or minus 4 mmol/l

›Albumin-corrected AG: add 2.5 mmol/l per 1 g/dL albumin below 4 g/dL

›High anion gap: consider GOLD MARRK causes

›Glycols, Oxoproline, Lactate, D-lactate, Methanol, Aspirin, Renal failure, Rhabdomyolysis, Ketoacidosis

02History/hx77

Symptom characterization

›Core symptoms of metabolic acidosis

›Dyspnea and Kussmaul respirations

›Deep labored breathing as compensation for low pH

›Progression from tachypnea to Kussmaul pattern with severity

›Nausea and vomiting

›Common in DKA, uremia, and toxic ingestions

›Bilious emesis in severe ketoacidosis

›Abdominal pain

›DKA-associated ileus or pan-like pain

›Mesenteric ischemia as cause of lactic acidosis

›Neurologic symptoms

›Confusion, lethargy, or obtundation with severe acidemia

›Visual changes pathognomonic for methanol poisoning

›Seizures suggesting toxic alcohol, uremia, or profound acidemia

›Onset and tempo

›Acute onset over hours

›Toxic ingestion, DKA, lactic acidosis from sepsis

›Hemodynamic collapse

›Subacute over days to weeks

›Progressive renal failure, alcoholic ketoacidosis

›Diarrheal illness with bicarbonate loss

Trigger and exposure history

›Ingestion history

›Methanol sources

›Windshield washer fluid, industrial solvents, illicitly produced alcohol

›Onset of visual symptoms 6 to 24 hours after ingestion

›Ethylene glycol sources

›Antifreeze, coolant products

›Calcium oxalate crystalluria as late finding

›Salicylate ingestion

›Aspirin, topical salicylate products

›Mixed respiratory alkalosis plus HAGMA pattern

›Iron, isoniazid, cyanide exposure

›Intentional or accidental ingestion

›Occupational exposures

›Medication review

›High-risk medications for HAGMA

›Metformin, especially with renal impairment or sepsis

›Linezolid, nucleoside reverse transcriptase inhibitors

›High-risk medications for NAGMA

›Topiramate, acetazolamide, zonisamide (carbonic anhydrase inhibitors)

›SGLT2 inhibitors (euglycemic DKA risk)

›Amphotericin B, spironolactone, amiloride

›Recent illness or triggers

›Missed insulin doses or sick-day insulin management failure

›Diarrheal illness with volume depletion

›Recent large-volume normal saline resuscitation

Risk factor assessment

›Medical history risks

›Diabetes mellitus

›Type 1 DKA risk with insulin omission or illness

›Type 2 SGLT2 inhibitor-related euglycemic DKA

›Chronic kidney disease or ESRD

›Baseline bicarbonate level and dialysis schedule

›Missed dialysis sessions

›Sepsis and shock states

›Accounts for approximately 50% of HAGMA cases via lactic acidosis

›Prior infections and source identification

›Chronic liver disease

›Impaired lactate clearance

›Alcoholic ketoacidosis risk

›Social and substance history

›Alcohol use disorder

›Alcoholic ketoacidosis trigger (binge with poor oral intake)

›Methanol or toxic alcohol ingestion risk

›Intentional overdose risk

›Psychiatric history and prior attempts

›Access to medications or household chemicals

›Homelessness or poverty

›Methanol or hand sanitizer ingestion

›Poor access to insulin or dialysis

Past surgical and family history

›Surgical history

›Short bowel syndrome (D-lactic acidosis risk)

›Ureterosigmoidostomy or urinary diversion (NAGMA from urine-bowel contact)

›Recent abdominal surgery (mesenteric ischemia risk)

›Family history

›Type 1 diabetes

›Inherited metabolic disorders (organic acidemias in pediatric context)

›Familial renal tubular acidosis

03Physical Exam/exam54

Vital signs and general appearance

›Stability snapshot

›Respiratory rate

›Tachypnea with Kussmaul pattern (deep, labored, regular)

›Fatigue progression with rising rate and decreasing depth

›Blood pressure

›Hypotension indicating shock as cause or consequence

›SBP <90 mmHg or MAP <65 mmHg requiring immediate response

›Heart rate

›Tachycardia from acidemia, volume depletion, or sympathetic activation

›Bradycardia or irregular rhythm suggesting severe hyperkalemia

›Temperature

›Fever pointing to sepsis as lactic acidosis cause

›Hypothermia in severe shock or alcohol intoxication

›General appearance

›Level of consciousness

›GCS score trend

›Obtundation suggesting severe acidemia or toxic ingestion

›Signs of dehydration

›Dry mucous membranes

›Reduced skin turgor

Targeted organ exam

›HEENT examination

›Breath quality

›Fruity or acetone odor suggesting DKA or isopropyl alcohol

›No distinctive odor does not exclude toxic alcohol

›Visual acuity

›Any visual disturbance or blurring is methanol until proven otherwise

04Differential Diagnosis/ddx66

High anion gap metabolic acidosis causes

›GOLD MARRK mnemonic

›Glycols

›Ethylene glycol: ICD-10 T52.8

›Propylene glycol (IV medications, lorazepam infusions)

›5-Oxoproline (pyroglutamic acid)

›Chronic acetaminophen use in malnourished patients

›Often missed, rare but important

›L-Lactate (most common HAGMA cause)

›Sepsis, shock, mesenteric ischemia, seizures, liver failure

›ICD-10 E87.2 acidosis, lactic acidosis

›D-Lactate

›Short bowel syndrome with bacterial overgrowth

›Standard lactate assay does not detect D-lactate

›Methanol

›ICD-10 T51.1

›Visual symptoms and high osmolal gap

›Aspirin and salicylates

›ICD-10 T39.01

›Mixed respiratory alkalosis plus HAGMA

›Renal failure

›Advanced CKD or ESRD with phosphate and sulfate accumulation

›ICD-10 N18.6

›Rhabdomyolysis

›Massive cell lysis releasing organic acids

›CK markedly elevated, myoglobinuria

›Ketoacidosis

›DKA: ICD-10 E10.10, E11.10

05Laboratory Tests/lt69

Core diagnostic workup

›Arterial or venous blood gas

›pH confirming acidemia (<7.35)

›ABG preferred for precise pCO2 and oxygenation assessment

›VBG acceptable for pH and HCO3 screening (pH correlation within 0.03 units)

›HCO3 (primary deficit)

›Mild: 15 to 22 mmol/l

›Moderate: 10 to 15 mmol/l

›Severe: <10 mmol/l

›pCO2 compensation adequacy

›Expected pCO2 by Winter's formula: 1.5 times HCO3 plus 8 plus or minus 2 mmHg

›Lower than expected pCO2 suggests concurrent respiratory alkalosis

›Higher than expected pCO2 suggests concurrent respiratory acidosis

›Basic metabolic panel

›Sodium, chloride, bicarbonate for anion gap calculation

›AG = Na minus (Cl plus HCO3); normal 12 plus or minus 4 mmol/l

›Always albumin-correct: add 2.5 per 1 g/dL albumin below 4 g/dL

›Potassium

›Acidemia shifts K extracellularly (rise 0.4 to 1.2 mmol/l per 0.1 pH unit drop)

›Correction of acidosis will lower K: replete before and during treatment

›BUN and creatinine

›AKI or CKD contribution to acidosis

›Dialysis threshold assessment

›Glucose

›Hyperglycemia in DKA

›Normal glucose with ketosis in SGLT2 inhibitor euglycemic DKA

Targeted diagnostic labs

›Serum lactate

›Essential in all HAGMA workup

›AG has <80% sensitivity for elevated lactate

›Level >2 mmol/l indicating hypoperfusion or Type A lactic acidosis

›Level >4 mmol/l indicating severe hypoperfusion and high mortality

›Repeat within 2 hours if initial elevation and treatment initiated

›Serum ketones

›Beta-hydroxybutyrate preferred over urine ketones

›More sensitive and quantitative

›Target <1 mmol/l for DKA resolution

›Urine ketones acceptable if BHB unavailable

›Osmolality and osmolal gap

›Measured serum osmolality

›Calculated: 2(Na) plus glucose/18 plus BUN/2.8 plus ethanol/4.6 (in SI units: 2Na plus glucose plus urea)

›Gap: measured minus calculated; normal <10 mOsm/kg

›Gap >10 mOsm/kg suggesting toxic alcohol or unmeasured osmoles

›Serum methanol and ethylene glycol levels

›Order when osmolal gap elevated or clinical suspicion

›Results often delayed; do not wait before treatment

›Serum albumin

›Mandatory for anion gap correction

›Hypoalbuminemia common in critically ill patients and masks HAGMA

›Salicylate and acetaminophen levels

›All intentional ingestions regardless of history

›Salicylate >3.6 mmol/l (50 mg/dL) associated with serious toxicity

Targeted etiology labs

›Urine studies for NAGMA differentiation

›Urine anion gap: Na plus K minus Cl

›Negative (less than zero): GI bicarbonate loss, renal tubular function intact

›Positive (greater than zero): RTA, impaired renal ammonium excretion

›Urine pH

›Cannot acidify below pH 5.5 in distal RTA despite systemic acidemia

›Calcium oxalate crystals

›Pathognomonic for ethylene glycol poisoning (late finding)

›Creatine kinase

›Rhabdomyolysis screen when myalgias or pigmented urine

›Level >5000 IU/L associated with AKI risk

›Liver function tests

›Impaired lactate clearance in hepatic failure

›Acute hepatic necrosis as lactic acidosis cause (ischemic hepatitis)

›Delta-delta ratio analysis

›Change in AG divided by change in HCO3 from normal (12 and 24 respectively)

›Ratio 1 to 2 suggesting pure HAGMA

›Ratio <1 suggesting concurrent NAGMA

›Ratio >2 suggesting concurrent metabolic alkalosis

06Diagnostic Tests/dt65

Scoring Systems

›Severity stratification tools

›pH-based severity classification

›Mild: pH 7.30 to 7.35, HCO3 15 to 22 mmol/l

›Moderate: pH 7.20 to 7.30, HCO3 10 to 15 mmol/l

›Severe: pH <7.20, HCO3 <10 mmol/l

›Critical: pH <7.10 with hemodynamic compromise

›SOFA score for sepsis-related lactic acidosis

›Score of 2 or more points above baseline indicates sepsis

›Organ dysfunction assessment across 6 domains

›DKA severity criteria (ADA)

›Mild DKA: pH 7.25 to 7.30, HCO3 15 to 18 mmol/l, alert

›Moderate DKA: pH 7.00 to 7.24, HCO3 10 to 14 mmol/l, alert or drowsy

›Severe DKA: pH <7.00, HCO3 <10 mmol/l, stupor or coma

›Anion gap analysis algorithm

›Step 1: Calculate corrected anion gap

›Step 2: If elevated AG, check delta-delta ratio

›Step 3: Apply Winter's formula for respiratory compensation adequacy

›Step 4: Osmolal gap when toxic alcohol suspected

MRI

›MRI role in metabolic acidosis

›Brain MRI for methanol or ethylene glycol toxicity

›Putaminal necrosis: bilateral basal ganglia T2/FLAIR hyperintensity in methanol

›White matter edema in severe methanol poisoning

›Diffuse cortical restriction in profound anoxic or toxic injury

›DWI restriction pattern

›Correlates with prognosis

›Limitations in acute setting

07Disposition/dispo43

ICU admission criteria

›Criteria for intensive care level

›Severe acidemia

›pH <7.20 or HCO3 <10 mmol/l

›Rapidly worsening despite initial treatment

›Hemodynamic instability

›Persistent hypotension requiring vasopressors

›Lactate >4 mmol/l or rising despite resuscitation

›Toxic alcohol ingestion

›Any confirmed or highly suspected methanol or ethylene glycol

›Fomepizole plus hemodialysis planning

›Severe DKA

›pH <7.00 or HCO3 <10 mmol/l with altered consciousness

›Hemodynamic instability

›Respiratory failure or impending arrest

›Intubation requirement or high-flow oxygen need

›Renal replacement therapy need

›Severe AKI with refractory acidosis or hyperkalemia

Floor and telemetry admission

›Criteria for general inpatient care

›Moderate acidemia

›pH 7.20 to 7.30 requiring IV treatment

›Clinical improvement trajectory

›DKA with stable hemodynamics

›Responding to initial fluid and insulin therapy

›pH above 7.10 and hemodynamically stable

›Hyperkalemia requiring monitoring

›K above 5.5 mmol/l with ECG changes

08Treatment/t120

Initial stabilization for all causes

›Resuscitation priorities

›IV access and monitoring

›Two large-bore IV lines or central access for unstable patients

›Continuous cardiac monitoring and pulse oximetry

›Arterial line for hemodynamically unstable patients requiring frequent ABGs

›Fluid resuscitation

›Balanced crystalloids preferred (Lactated Ringer or Plasmalyte)

›Avoid normal saline to prevent iatrogenic hyperchloremic acidosis

›20 to 30 mL/kg initial bolus in sepsis; reassess after each liter

›Treat the underlying cause

›Most critical intervention across all etiologies

›Source control in sepsis within 6 to 12 hours

›Antidote administration in toxic ingestion

DKA treatment

›Fluid resuscitation in DKA

›Normal saline acceptable for initial resuscitation in DKA

›1 L over first hour for hemodynamic stabilization

›Transition to balanced crystalloids once stable

›Ongoing fluid rate

›250 to 500 mL/hour based on clinical assessment

›Add dextrose when glucose <14 mmol/l to prevent hypoglycemia

›Insulin therapy in DKA

›Insulin initiation timing

›Start insulin 1 to 2 hours after initiating fluids

›Do not start until potassium is above 3.5 mmol/l

›Regular insulin infusion

›0.1 units/kg/hour continuous IV infusion

›Alternatively: 0.1 units/kg IV bolus then 0.1 units/kg/hour

›Target glucose fall of 2.8 to 4.2 mmol/l per hour

›Subcutaneous insulin option for mild to moderate DKA

›Rapid-acting insulin 0.2 to 0.3 units/kg every 2 to 4 hours

›Appropriate only with pH above 7.25 and able to tolerate oral intake

›Potassium repletion in DKA

›Potassium monitoring

›Check every 1 to 2 hours during active insulin therapy

›Acidosis correction will drop potassium significantly

›Repletion thresholds

›K 3.5 to 5.5 mmol/l: add 20 to 40 mmol/l to IV fluids

›K <3.5 mmol/l: hold insulin, give 40 mmol/hour until K above 3.5

›K >5.5 mmol/l: no repletion, monitor every 2 hours

›DKA resolution criteria

›Glucose <11 mmol/l

›HCO3 >=15 mmol/l

›Venous pH >7.30

›Beta-hydroxybutyrate <1 mmol/l preferred end point

Lactic acidosis treatment

›Volume resuscitation and vasopressors

›Norepinephrine for septic shock

›Starting dose 0.01 to 0.1 mcg/kg/minute

›Titrate to MAP >=65 mmHg

›Preferred first-line vasopressor in sepsis (Class I recommendation)

›Vasopressin adjunct

›0.03 units/minute fixed dose

›Addition for norepinephrine-sparing when doses escalating

›Sodium bicarbonate in lactic acidosis

›Routine use not supported in lactic acidosis without AKI

›Does not improve hemodynamics in most studies

›Increases pCO2 in closed system

›Consider when pH <7.15 with concurrent AKI

›BICARICU-2 trial (2025): bicarbonate reduced need for RRT when pH <=7.20 and moderate-to-severe AKI

›BICARICU-1 showed mortality benefit in AKI subgroup (46% vs 63%)

Toxic alcohol treatment

›Fomepizole (alcohol dehydrogenase inhibitor)

›Indication

›Confirmed or strongly suspected methanol or ethylene glycol ingestion

›Do not delay for confirmatory levels when clinical suspicion high

›Dosing protocol

›Loading dose: 15 mg/kg IV over 30 minutes

›Maintenance: 10 mg/kg IV every 12 hours for 4 doses

›Then 15 mg/kg IV every 12 hours until methanol/EG undetectable

›Hemodialysis indications alongside fomepizole

›pH <=7.15 despite treatment

›Methanol or EG level >50 mg/dL (>16 mmol/l methanol, >8 mmol/l EG)

›Visual changes, seizures, coma (methanol)

›AKI or renal failure (ethylene glycol)

›EXTRIP workgroup recommendations (2023)

Salicylate toxicity treatment

›Urine alkalinization

›Sodium bicarbonate infusion

›150 mmol/l sodium bicarbonate in D5W; infuse at 2 to 3 mL/kg/hour

›Target urine pH 7.5 to 8.0

›Monitor serum potassium and pH hourly

›Mechanism: ion trapping increases renal salicylate clearance

›Hemodialysis for salicylate toxicity

›Indications

›Serum salicylate >100 mg/dL (>7.2 mmol/l)

›Severe acidemia with AKI

›CNS symptoms including seizures or coma

›Pulmonary edema

›Avoid intubation when possible

›Mechanical ventilation risks loss of respiratory alkalosis compensation

›If intubation required, set respiratory rate to match pre-intubation rate

Sodium bicarbonate therapy

›Cardiac arrest with metabolic acidosis

›Sodium bicarbonate 1 to 2 mmol/kg IV push initially

›Then 50 mmol every 5 to 10 minutes guided by ABG

›AHA 2025 guidelines: consider in cardiac arrest with hyperkalemia or TCA toxicity

›Non-arrest severe acidemia (pH <7.20 with AKI)

›Sodium bicarbonate infusion

›2 to 5 mmol/kg IV over 4 to 8 hours

›Target HCO3 approximately 20 mmol/l by end of day 1

›Avoid full correction within 24 hours to prevent rebound alkalosis

›Monitoring during bicarbonate infusion

›Serial ABG every 2 to 4 hours

›Serum potassium every 2 hours (bicarbonate drives K intracellularly)

›Sodium and volume status (risk of hypernatremia and volume overload)

Chronic CKD-related acidosis treatment

›Oral alkali supplementation

›Sodium bicarbonate tablets

›Starting dose 650 mg three times daily (7.7 mmol per tablet)

›Titrate to HCO3 >=22 mmol/l

›KDIGO 2024 guidelines support maintaining HCO3 in normal range

›Sodium citrate solution (Shohl's solution)

›Alternative oral alkali option

›More palatable for some patients

›Dietary modification adjunct

›Plant-dominant diets reduce net endogenous acid production

›Comparable to oral bicarbonate in small RCTs for CKD-related acidosis

›Avoid high animal protein and processed food acid load

Alcoholic ketoacidosis treatment

›Dextrose-containing IV fluids

›D5W or D5 normal saline at 100 to 200 mL/hour

›Stimulates insulin release to suppress ketogenesis

›Continue until ketosis resolves and oral intake restored

›Thiamine before dextrose

›100 mg IV thiamine to prevent Wernicke encephalopathy

›Essential in malnourished or alcohol-dependent patients

09Special Populations/sp82

Pregnancy

›Physiologic considerations

›Baseline respiratory alkalosis in pregnancy

›Normal HCO3 in pregnancy: 18 to 22 mmol/l (lower than non-pregnant baseline)

›Normal pH slightly alkalemic at 7.40 to 7.45

›Apparent bicarbonate deficit may be misleading

›Increased risk of DKA

›Insulin resistance of pregnancy increases DKA risk in Type 1 and Type 2 diabetes

›DKA may occur at lower glucose levels (euglycemic DKA risk even without SGLT2 inhibitors)

›Uteroplacental perfusion threatened by acidemia

›Fetal acidosis occurs at lower maternal pH thresholds

›Aggressive maternal treatment protects fetal outcome

›Treatment modifications in pregnancy

›Insulin dosing for DKA

›Similar protocol to non-pregnant adults but with lower glucose targets

›Target glucose 5.6 to 7.8 mmol/l to avoid fetal hypoglycemia

›Fomepizole safety in pregnancy

›Limited data; use when toxic alcohol ingestion confirmed or strongly suspected

›Benefit outweighs theoretical risk in life-threatening toxic alcohol ingestion

›Sodium bicarbonate use

›Generally safe in pregnancy for severe acidemia

›Monitor for fetal CO2 production and hypernatremia

›Fetal monitoring

›Continuous fetal monitoring when gestational age >24 weeks

›Obstetric consultation for severe acidemia

Geriatric

›Physiologic vulnerabilities

›Reduced renal reserve

›Decreased GFR with age reduces acid excretion capacity

›Prone to rapid decompensation with acute illness

›Blunted compensatory responses

›Kussmaul respirations may be less pronounced

›Fever may be absent in sepsis

›Higher chronic CKD prevalence

›Baseline bicarbonate often lower

›Less reserve before critical threshold crossed

›Medication risks in older adults

›Metformin risks amplified with age-related renal decline

›Hold metformin when GFR <30 mL/min/1.73m2 or acute illness

›SGLT2 inhibitor euglycemic DKA risk

›Increased in older adults during illness or surgery

›Hold SGLT2 inhibitors during acute illness

›Carbonic anhydrase inhibitors

›Topiramate and acetazolamide cause NAGMA at standard doses

›Renal dose adjustment necessary

›Disposition considerations

›Lower threshold for ICU admission in frail older adults

›Limited physiologic reserve for clinical deterioration

›Aspiration risk during treatment (volume loading, altered consciousness)

›Polypharmacy interaction review

›Multiple acid-altering medications common

›Drug-drug interactions affecting renal function

Pediatrics

›Common pediatric etiologies

›DKA most common HAGMA in children

›Type 1 DKA accounts for majority of pediatric HAGMA

›Cerebral edema risk during DKA treatment (2% to 3% incidence)

›Inherited organic acidemias

›Methylmalonic acidemia, propionic acidemia, isovaleric acidemia

›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

10Background/b82

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

11Patient Discharge Instructions/pdi30

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

12References/r24

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

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Reviewed by SymptomDx Medical Team · Last reviewed August 18, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.