Electrolytes — Phosphate

109. Hypophosphatemia

low phosphate · refeeding syndrome / alcohol use disorder / malnutrition / DKA treatment · the silent cause of weaning failure & weakness · co-replete with K and Mg · Super Compact

Sx: mild often asymptomatic · severe (<1–1.5 mg/dL): muscle weakness (including diaphragm → respiratory failure/ventilator weaning failure), rhabdomyolysis, hemolysis, ↓cardiac contractility/arrhythmia, confusion/seizures, paresthesias · impaired oxygen delivery (↓2,3-DPG) (suspect in the malnourished/alcoholic patient who can't wean from the vent or is mysteriously weak)

Neg: denies that K/Mg are unchecked (co-deplete — replace together) · denies that this is a transient post-prandial/insulin shift only · denies missed refeeding setup (don't feed aggressively before checking/repleting phos) · denies ongoing renal wasting unaddressed

SHx: malnutrition/chronic alcohol use (depleted stores) · refeeding (carb load → insulin → intracellular phos shift — the classic precipitant) · DKA treatment (insulin drives phos into cells) · diarrhea/malabsorption, phosphate binders/antacids · vitamin D deficiency · hyperparathyroidism · sepsis

Etiology: transcellular shift (most acute inpatient cases) — refeeding (insulin surge with carbohydrate), insulin therapy in DKA, respiratory alkalosis, recovery phase of illness · renal loss (hyperparathyroidism, vitamin D deficiency, Fanconi/tubular, diuretics, post-ATN/transplant diuresis) · decreased intake/absorption (malnutrition, alcohol, phosphate binders, antacids, chronic diarrhea, vitamin D deficiency) · alcohol use disorder combines several

RF: malnutrition/alcohol use disorder · refeeding after starvation · DKA on insulin · critical illness/sepsis · hyperparathyroidism · long-term antacid/binder use

Data: serum phosphate · K, Mg, Ca (ALWAYS — co-depleted, esp in refeeding/alcohol) · BMP/renal function · in refeeding-risk patients: check phos before and serially during feeding · consider 25-OH vitamin D, PTH, urine phosphate / fractional excretion (renal wasting [high] vs shift/GI [low/conserving]) · CK if rhabdo suspected

DDx: redistribution/shift (refeeding, DKA insulin, alkalosis — context) · renal wasting (high urine phos — hyperPTH, Fanconi, diuretics) · decreased intake/absorption (malnutrition, binders, vit D) · accompanying hypoK/hypoMg (check panel)

Home Meds: review/hold phosphate binders, calcium/aluminum/magnesium antacids · review diuretics · correct vitamin D deficiency · advance nutrition cautiously if refeeding risk

Plan

CONSULT: Nutrition/Dietitian (refeeding protocol, malnutrition) · Nephrology (renal wasting/refractory) · ICU (severe — respiratory failure, arrhythmia, ventilator weaning) · GI (malabsorption)

– Assess severity + symptoms: severe (<1–1.5) or symptomatic (respiratory/cardiac/neuro) → IV phosphate; mild–moderate asymptomatic → oral
– IV phosphate (severe/symptomatic/NPO): sodium phosphate or potassium phosphate IV (e.g. ~0.08–0.16 mmol/kg, or institutional weight-based protocol — typically 15–30 mmol over 4–6 h), infused slowly; choose potassium phosphate if also hypokalemic, sodium phosphate if not; recheck after dosing
  • Cautions: infuse slowly (rapid IV phosphate → hypocalcemia, calcium-phosphate precipitation, arrhythmia, hypotension); reduce dose in renal impairment; monitor Ca, K, renal function
– Oral phosphate (mild–moderate): oral phosphate salts (e.g. sodium/potassium phosphate tabs) — limited by diarrhea
– CO-REPLETE potassium and magnesium — these co-deplete (especially refeeding and alcohol use), and hypomagnesemia perpetuates the others; replace together
– Refeeding syndrome — prevent and manage: in high-risk (chronic alcohol, severe malnutrition, prolonged NPO/starvation, anorexia) start nutrition LOW and advance SLOWLY, give thiamine before/with carbohydrate, check and replete phosphate, potassium, magnesium before and serially during feeding; hold/slow feeding advancement if electrolytes drop
– DKA-related: phosphate falls as insulin drives it intracellularly; replace if severe/symptomatic (routine aggressive repletion not required) — and use potassium phosphate as part of K repletion when both are low
– Treat the cause: nutrition, alcohol cessation support, stop binders/antacids, correct vitamin D, address renal wasting
– Phosphate is the electrolyte people forget until a malnourished or alcoholic patient can't be weaned from the ventilator. Check it (with K and Mg) before you start feeding a high-risk patient — refeeding can crash all three — and feed low and slow with thiamine on board.
– PT/OT: monitor weakness; mobilize as able
– Trend: phosphate, potassium, magnesium, calcium, renal function, respiratory status (esp ventilated), CK if rhabdo
– Escalation triggers: respiratory failure/weaning failure, arrhythmia, rhabdomyolysis, or seizures → ICU + IV phosphate; refractory → renal wasting workup; refeeding electrolyte crash → slow/hold feeds + aggressive repletion
– Discharge checklist: phosphate (and K/Mg) normalized; cause addressed (nutrition plan, alcohol support, binders/antacids reviewed, vitamin D); refeeding-safe nutrition plan if applicable; oral phosphate maintenance if needed; outpatient electrolyte recheck + follow-up; return precautions (weakness, breathlessness, palpitations, confusion)

109. Hypophosphatemia

complete reference · refeeding syndrome + alcohol use disorder + malnutrition + DKA treatment · co-repletion with K and Mg · Full Card

Symptoms / Associated Sx

• Mild hypophosphatemia is often asymptomatic

• Severe hypophosphatemia (<1–1.5 mg/dL) causes muscle weakness — including of the diaphragm, leading to respiratory failure and failure to wean from the ventilator — along with rhabdomyolysis, hemolysis, reduced cardiac contractility and arrhythmia, confusion, seizures, and paresthesias

• Impaired oxygen delivery from reduced 2,3-DPG

• Suspect it in the malnourished or alcoholic patient who cannot wean from the ventilator or is unexplainably weak

Neg

• Pt denies unchecked potassium and magnesium — they co-deplete and must be replaced together

• Pt denies that the value reflects only a transient post-prandial or insulin-driven shift

• Pt denies a missed refeeding setup (avoid aggressive feeding before checking and repleting phosphate) and denies unaddressed ongoing renal wasting

Social History (SHx)

• Malnutrition and chronic alcohol use (depleted stores)

• Refeeding (a carbohydrate load triggers insulin, which shifts phosphate into cells — the classic precipitant)

• DKA treatment (insulin drives phosphate intracellularly)

• Diarrhea/malabsorption, phosphate binders and antacids, vitamin D deficiency, hyperparathyroidism, and sepsis

Main Etiology

• Transcellular shift (most acute inpatient cases): refeeding (the insulin surge with carbohydrate), insulin therapy in DKA, respiratory alkalosis, and the recovery phase of illness

• Renal loss: hyperparathyroidism, vitamin D deficiency, Fanconi syndrome and tubular disorders, diuretics, and the post-ATN or post-transplant diuresis

• Decreased intake/absorption: malnutrition, alcohol use, phosphate binders, antacids, chronic diarrhea, and vitamin D deficiency

• Alcohol use disorder combines several of these mechanisms

RF

• Modifiable: nutrition status, alcohol use, antacid/binder use, vitamin D status

• Non-modifiable: critical illness, hyperparathyroidism, and tubular disorders

Data

• Serum phosphate

• Potassium, magnesium, and calcium — always (co-depleted, especially in refeeding and alcohol use)

• BMP/renal function

• In refeeding-risk patients, check phosphate before and serially during feeding

• 25-OH vitamin D, PTH, and urine phosphate or fractional excretion (separates renal wasting, with high urine phosphate, from a shift or GI cause with appropriate conservation); CK if rhabdomyolysis is suspected

DDx

Redistribution/shift (refeeding, DKA insulin, alkalosis — by context) · renal wasting (high urine phosphate — hyperparathyroidism, Fanconi, diuretics) · decreased intake/absorption (malnutrition, binders, vitamin D deficiency) · accompanying hypokalemia/hypomagnesemia (check the panel)

Home Meds

• Review/hold: phosphate binders and calcium/aluminum/magnesium antacids

• Review: diuretics; correct vitamin D deficiency

• Advance nutrition cautiously in patients at refeeding risk

Plan

CONSULT: Nutrition/Dietitian (refeeding protocol, malnutrition) · Nephrology (renal wasting, refractory cases) · ICU (severe — respiratory failure, arrhythmia, ventilator weaning) · GI (malabsorption)

• Assess severity and symptoms: severe (<1–1.5) or symptomatic (respiratory, cardiac, or neurologic) hypophosphatemia warrants IV phosphate; mild-to-moderate asymptomatic hypophosphatemia is treated orally

• IV phosphate for severe, symptomatic, or NPO patients: sodium phosphate or potassium phosphate IV (approximately 0.08–0.16 mmol/kg, or per a weight-based institutional protocol — typically 15–30 mmol over 4–6 hours), infused slowly; choose potassium phosphate if the patient is also hypokalemic and sodium phosphate if not, and recheck after dosing

• Cautions with IV phosphate: infuse slowly, since rapid administration causes hypocalcemia, calcium-phosphate precipitation, arrhythmia, and hypotension; reduce the dose in renal impairment; and monitor calcium, potassium, and renal function

• Oral phosphate for mild-to-moderate cases: oral phosphate salts (sodium or potassium phosphate tablets), limited by diarrhea at higher doses

• Co-replete potassium and magnesium: these co-deplete (especially in refeeding and alcohol use), and hypomagnesemia perpetuates the others — replace them together

• Refeeding syndrome — prevent and manage: in high-risk patients (chronic alcohol use, severe malnutrition, prolonged NPO/starvation, anorexia nervosa), start nutrition low and advance slowly, give thiamine before or with the carbohydrate load, and check and replete phosphate, potassium, and magnesium before and serially during feeding, holding or slowing the advancement if electrolytes fall

• DKA-related hypophosphatemia: phosphate falls as insulin drives it intracellularly; replace it when severe or symptomatic (routine aggressive repletion is not required), using potassium phosphate as part of potassium repletion when both are low

• Treat the cause: nutrition, alcohol cessation support, discontinuation of binders/antacids, correction of vitamin D, and management of renal wasting

• PT/OT: monitor for weakness and mobilize as able

• Trend: phosphate, potassium, magnesium, calcium, renal function, respiratory status (especially in ventilated patients), and CK if rhabdomyolysis is a concern

• Escalation triggers: respiratory or ventilator-weaning failure, arrhythmia, rhabdomyolysis, or seizures → ICU and IV phosphate; refractory cases → a renal-wasting workup; an electrolyte crash during refeeding → slow or hold feeds and replete aggressively

• Discharge checklist: phosphate (and potassium and magnesium) normalized; the cause addressed (a nutrition plan, alcohol support, review of binders/antacids, vitamin D); a refeeding-safe nutrition plan if applicable; oral phosphate maintenance if needed; an outpatient electrolyte recheck with follow-up; return precautions for weakness, breathlessness, palpitations, or confusion

Red Flags

• Diaphragmatic weakness causing respiratory failure or inability to wean from the ventilator → ICU and IV repletion

• Rhabdomyolysis, hemolysis, or arrhythmia from severe hypophosphatemia → urgent treatment

• Refeeding in a high-risk patient → a sudden crash in phosphate, potassium, and magnesium → slow feeds and replete

• Seizures or profound confusion → severe depletion → IV phosphate

• Rapid IV phosphate infusion → hypocalcemia and calcium-phosphate precipitation → infuse slowly

Senior IM Resident Pearls

• Phosphate is the forgotten electrolyte behind weaning failure. A malnourished or alcoholic patient who can't come off the ventilator or is mysteriously weak deserves a phosphate check.

• Refeeding crashes phosphate, potassium, and magnesium together. In high-risk patients, feed low and slow, give thiamine first, and check all three before and during feeding.

• Match the phosphate salt to the potassium. Use potassium phosphate when the patient is also hypokalemic, and sodium phosphate when potassium is fine — it lets you fix two problems with one infusion.

• Infuse IV phosphate slowly. Fast administration precipitates with calcium and can cause hypocalcemia and arrhythmia — respect the rate.

• Thiamine before glucose, always, in the malnourished or alcoholic patient — refeeding with carbohydrate before thiamine risks Wernicke encephalopathy.

• Reduce the dose in renal impairment — phosphate accumulates and can overshoot into hyperphosphatemia.

• Common mistake: aggressively feeding a starved patient without first checking and repleting phosphate, potassium, and magnesium — the classic, preventable refeeding catastrophe.

Electrolytes — Phosphate

110. Hyperphosphatemia

high phosphate · CKD / ESRD / tumor lysis syndrome · usually impaired renal excretion or massive cell release · watch the calcium (precipitation, hypocalcemia) · Super Compact

Sx: phosphate itself usually asymptomatic acutely · symptoms come from accompanying hypocalcemia (tetany, paresthesias, seizures, ↑QT/arrhythmia — from calcium-phosphate precipitation lowering ionized Ca) · chronic (CKD): vascular/soft-tissue calcification, renal osteodystrophy, pruritus · acute massive rise (tumor lysis): AKI, hypocalcemia (the danger is the calcium it drags down and the tissue it precipitates in)

Neg: denies spurious (hemolysis, paraproteinemia) · denies missed tumor lysis (with hyperK, hyperuricemia, AKI) · denies large exogenous load (phosphate enemas/laxatives, IV phosphate) · denies that hypocalcemia is being mistreated with large calcium into high phosphate (precipitation risk)

SHx: CKD/ESRD + dialysis status · malignancy/chemotherapy (tumor lysis) · hypoparathyroidism · vitamin D excess · phosphate-containing bowel preps/enemas · rhabdomyolysis · large tissue injury

Etiology: impaired renal excretion (commonest) — CKD/ESRD (reduced GFR), hypoparathyroidism · massive phosphate release/load — tumor lysis syndrome, rhabdomyolysis, hemolysis, bowel ischemia, exogenous (phosphate enemas/laxatives, IV phosphate) · transcellular shift out of cells — acidosis (DKA, lactic), tissue catabolism · vitamin D excess

RF: CKD/ESRD · malignancy on chemotherapy (high tumor burden) · rhabdomyolysis · phosphate bowel preps in elderly/CKD · hypoparathyroidism

Data: serum phosphate · calcium (ionized/corrected — guides urgency) · BMP/renal function · if tumor lysis suspected: K, uric acid, LDH, calcium, renal function · PTH, vitamin D (chronic/CKD context) · consider CK (rhabdo), hemolysis labs · ECG if hypocalcemia (↑QT)

DDx: CKD/ESRD (chronic, ↓GFR) · tumor lysis (↑K, ↑uric acid, ↑phos, ↓Ca, AKI, on chemo) · rhabdomyolysis (↑CK, ↑K) · exogenous load (enemas/laxatives) · hypoparathyroidism (↓PTH, ↓Ca, ↑phos)

Home Meds: review/start phosphate binders (sevelamer, calcium acetate, lanthanum, ferric citrate — give with meals) · stop phosphate-containing enemas/laxatives, vitamin D/phosphate supplements · review/avoid calcium loads into very high phosphate · renally dose

Plan

CONSULT: Nephrology (CKD-MBD, ESRD, dialysis, severe/refractory) · Oncology (tumor lysis) · ICU (severe tumor lysis, symptomatic hypocalcemia)

– Identify acuity + cause: chronic CKD vs acute massive rise (tumor lysis/rhabdo) — drives urgency
– Acute severe (tumor lysis, rhabdomyolysis):
  • IV isotonic fluids to promote renal phosphate excretion + maintain urine output (if kidneys responsive)
  • Hemodialysis for severe hyperphosphatemia with renal failure, symptomatic hypocalcemia, or refractory tumor lysis — definitive removal
  • Manage accompanying tumor lysis: hydration, treat hyperkalemia (full cocktail — calcium gluconate 1–2 g IV for cardiac protection if ECG changes, insulin 10 u + D50 25 g, albuterol, binder/dialysis), rasburicase/allopurinol for uric acid, treat AKI
– Hypocalcemia management (caution): only treat symptomatic hypocalcemia (tetany, seizures, arrhythmia) with IV calcium — giving calcium into a high phosphate risks calcium-phosphate precipitation (metastatic calcification, worsening AKI); prioritize lowering the phosphate; use the minimum calcium to control symptoms
– Chronic (CKD/ESRD): dietary phosphate restriction + phosphate binders with meals (sevelamer, calcium acetate, lanthanum carbonate, ferric citrate — non-calcium binders preferred if calcium load/vascular calcification a concern); optimize dialysis (adequacy/frequency); manage CKD-MBD (PTH, vitamin D analogs, calcimimetics per nephrology)
– Stop the source: discontinue phosphate enemas/laxatives, phosphate/vitamin D supplements
– The phosphate number rarely hurts the patient directly — the calcium it pulls down does. Resist the urge to pour calcium into a high phosphate (it precipitates in tissues and kidneys); lower the phosphate first, and give calcium only for symptomatic hypocalcemia. In tumor lysis, dialysis handles phosphate, potassium, and uric acid at once.
– PT/OT: per underlying illness
– Trend: phosphate, calcium (ionized), potassium, uric acid, renal function/UOP (tumor lysis), ECG if hypocalcemia, dialysis response
– Escalation triggers: symptomatic hypocalcemia, severe tumor lysis, anuric/renal failure, or refractory → ICU/dialysis + nephrology/oncology; rising K/AKI in tumor lysis → urgent dialysis
– Discharge checklist: phosphate controlled + cause addressed; binder regimen + dietary counseling (CKD); dialysis plan optimized (ESRD); offending agents stopped (enemas/supplements); calcium/CKD-MBD plan; outpatient phosphate/calcium recheck + nephrology/oncology follow-up; return precautions (tetany/tingling, palpitations, decreased urination)

110. Hyperphosphatemia

complete reference · CKD + ESRD + tumor lysis syndrome · binders, dialysis, calcium caution · Full Card

Symptoms / Associated Sx

• Phosphate itself is usually asymptomatic acutely; symptoms arise from accompanying hypocalcemia (tetany, paresthesias, seizures, QT prolongation, and arrhythmia) as calcium-phosphate precipitation lowers the ionized calcium

• Chronic hyperphosphatemia in CKD causes vascular and soft-tissue calcification, renal osteodystrophy, and pruritus

• An acute massive rise, as in tumor lysis, causes AKI and hypocalcemia

• The danger lies in the calcium it drags down and the tissue in which it precipitates

Neg

• Pt denies a spurious value (hemolysis, paraproteinemia)

• Pt denies a missed tumor lysis syndrome (with hyperkalemia, hyperuricemia, and AKI) and denies a large exogenous load (phosphate enemas or laxatives, IV phosphate)

• Pt denies inappropriate treatment of the hypocalcemia with large calcium doses into a high phosphate (precipitation risk)

Social History (SHx)

• CKD/ESRD with dialysis status

• Malignancy and chemotherapy (tumor lysis)

• Hypoparathyroidism and vitamin D excess

• Phosphate-containing bowel preparations and enemas, rhabdomyolysis, and large tissue injury

Main Etiology

• Impaired renal excretion (the most common): CKD/ESRD (reduced GFR) and hypoparathyroidism

• Massive phosphate release or load: tumor lysis syndrome, rhabdomyolysis, hemolysis, bowel ischemia, and exogenous sources (phosphate enemas/laxatives, IV phosphate)

• Transcellular shift out of cells: acidosis (DKA, lactic acidosis) and tissue catabolism

• Vitamin D excess

RF

• Modifiable: phosphate-containing bowel preps (especially in the elderly and those with CKD), dietary phosphate, supplement use

• Non-modifiable: CKD/ESRD, high-tumor-burden malignancy on chemotherapy, and hypoparathyroidism

Data

• Serum phosphate

• Calcium (ionized or corrected) (guides urgency)

• BMP/renal function

• If tumor lysis is suspected: potassium, uric acid, LDH, calcium, and renal function

• PTH and vitamin D (in the chronic/CKD context); CK (rhabdomyolysis) and hemolysis labs; an ECG if there is hypocalcemia (QT prolongation)

DDx

CKD/ESRD (chronic, reduced GFR) · tumor lysis syndrome (high potassium, high uric acid, high phosphate, low calcium, AKI, on chemotherapy) · rhabdomyolysis (high CK, high potassium) · exogenous load (enemas/laxatives) · hypoparathyroidism (low PTH, low calcium, high phosphate)

Home Meds

• Review/start: phosphate binders (sevelamer, calcium acetate, lanthanum, ferric citrate), given with meals

• Stop: phosphate-containing enemas/laxatives and vitamin D/phosphate supplements

• Avoid large calcium loads into a very high phosphate; renally dose medications

Plan

CONSULT: Nephrology (CKD–mineral bone disease, ESRD, dialysis, severe/refractory cases) · Oncology (tumor lysis) · ICU (severe tumor lysis, symptomatic hypocalcemia)

• Identify the acuity and cause: chronic CKD versus an acute massive rise (tumor lysis, rhabdomyolysis), which drives the urgency

• Acute severe (tumor lysis, rhabdomyolysis):

• • IV isotonic fluids to promote renal phosphate excretion and maintain urine output, if the kidneys are responsive

• • Hemodialysis for severe hyperphosphatemia with renal failure, symptomatic hypocalcemia, or refractory tumor lysis — providing definitive removal

• • Manage accompanying tumor lysis: hydration; treatment of hyperkalemia with the full cocktail (calcium gluconate 1–2 g IV for cardiac protection if there are ECG changes, insulin 10 units IV with D50 25 g, nebulized albuterol, and a binder or dialysis); rasburicase or allopurinol for uric acid; and treatment of the AKI

• Hypocalcemia management with caution: treat only symptomatic hypocalcemia (tetany, seizures, arrhythmia) with IV calcium, because giving calcium into a high phosphate risks calcium-phosphate precipitation (metastatic calcification, worsening AKI) — prioritize lowering the phosphate and use the minimum calcium needed to control symptoms

• Chronic (CKD/ESRD): dietary phosphate restriction with phosphate binders taken with meals (sevelamer, calcium acetate, lanthanum carbonate, ferric citrate — non-calcium binders preferred when calcium load or vascular calcification is a concern), optimization of dialysis adequacy and frequency, and management of CKD–mineral bone disease (PTH, vitamin D analogs, calcimimetics per nephrology)

• Stop the source: discontinue phosphate enemas/laxatives and phosphate/vitamin D supplements

• PT/OT: guided by the underlying illness

• Trend: phosphate, ionized calcium, potassium, uric acid, renal function and urine output (in tumor lysis), an ECG if hypocalcemic, and the dialysis response

• Escalation triggers: symptomatic hypocalcemia, severe tumor lysis, an anuric/renal-failure state, or refractory hyperphosphatemia → ICU/dialysis with nephrology/oncology; rising potassium or AKI in tumor lysis → urgent dialysis

• Discharge checklist: phosphate controlled with the cause addressed; a binder regimen with dietary counseling (CKD); an optimized dialysis plan (ESRD); offending agents stopped (enemas, supplements); a calcium and CKD-MBD plan; an outpatient phosphate/calcium recheck with nephrology/oncology follow-up; return precautions for tetany/tingling, palpitations, or decreased urination

Red Flags

• Symptomatic hypocalcemia (tetany, seizures, arrhythmia) from acute hyperphosphatemia → cautious IV calcium and urgent phosphate lowering

• Tumor lysis syndrome with rising potassium, uric acid, and AKI → urgent hydration, rasburicase, and dialysis

• Severe hyperphosphatemia with renal failure → hemodialysis

• Giving calcium into a very high phosphate → calcium-phosphate precipitation and metastatic calcification

• Phosphate enema toxicity in an elderly or CKD patient → severe acute hyperphosphatemia

Senior IM Resident Pearls

• The phosphate rarely harms directly — the calcium it pulls down does. Symptoms track the hypocalcemia, so treat the calcium for symptoms while lowering the phosphate.

• Don't pour calcium into a high phosphate. The product precipitates in tissues and kidneys (metastatic calcification, worsening AKI) — give the minimum calcium for symptomatic hypocalcemia only.

• Dialysis is a three-for-one in tumor lysis, clearing phosphate, potassium, and uric acid simultaneously — escalate early in severe cases.

• Binders only work with food. They bind dietary phosphate in the gut, so timing them with meals is what makes them effective — a common adherence pitfall.

• Watch phosphate enemas in the elderly and in CKD — they can cause life-threatening acute phosphate nephropathy and hyperphosphatemia.

• Prefer non-calcium binders when vascular calcification or calcium load is a concern in chronic CKD management.

• Common mistake: reflexively treating the hypocalcemia of tumor lysis with aggressive calcium — it precipitates with the high phosphate; lower the phosphate first.

Electrolytes — Combined Derangements

111. Mixed Electrolyte Disorders

multiple simultaneous derangements · severe diarrhea / malnutrition / alcoholism / critical illness · the classic triad: low K + low Mg + low Phos · fix magnesium first, replete in concert · Super Compact

Sx: a composite of the individual deficits — weakness, cramps, arrhythmia (↑QT, ectopy, torsades), tetany/paresthesias, confusion/seizures, ileus, ventilator-weaning failure · features of the precipitating illness (volume depletion, malnutrition, withdrawal) (the danger is additive — combined hypoK + hypoMg + hypoCa is far more arrhythmogenic than any one alone; suspect the whole panel is off when one electrolyte is)

Neg: denies that only the most obvious abnormality was checked (must measure the full panel — K, Mg, Phos, Ca, Na) · denies treating K/Ca without Mg (refractory until Mg replaced) · denies aggressive refeeding before repletion · denies overlooking the acid-base picture (often coexists)

SHx: severe/chronic diarrhea or laxative misuse · malnutrition/refeeding, anorexia · alcohol use disorder (poor intake + losses + shifts — the prototype) · critical illness/sepsis, prolonged NPO · diuretics · short-gut/malabsorption · DKA treatment

Etiology: shared mechanisms hit several electrolytes at once · GI loss (diarrhea → K, Mg, bicarbonate; vomiting → K, Cl, alkalosis) · poor intake + depleted stores (malnutrition, alcohol) · renal wasting (diuretics, alcohol, hypomagnesemia driving K/Ca loss) · transcellular shifts (refeeding/insulin → Phos, K, Mg into cells) · hypomagnesemia as the linchpin (perpetuates refractory hypoK and hypoCa)

RF: alcohol use disorder · malnutrition/refeeding · chronic diarrhea/malabsorption · critical illness · diuretic use · prolonged NPO

Data: full electrolyte panel — Na, K, Mg, Phos, Ca (corrected/ionized), bicarbonate/BMP · ECG (↑QT, U waves, ectopy — arrhythmia risk) · acid-base (VBG; mixed metabolic disturbances common) · renal function · glucose/ketones (DKA, refeeding) · albumin (Ca correction) · in refeeding risk: check before feeding + serially · identify and quantify ongoing losses

DDx: diarrheal losses (low K/Mg, NAGMA) · alcohol/malnutrition (low K/Mg/Phos/Ca, thiamine deficit) · refeeding (falling Phos/K/Mg with feeding) · critical illness (multifactorial) · diuretic effect (low K/Mg, alkalosis)

Home Meds: review/hold diuretics, laxatives, PPIs (↓Mg) · alcohol cessation support · advance nutrition cautiously (refeeding) · renally dose · reconcile all contributors

Plan

CONSULT: Nutrition/Dietitian (refeeding, malnutrition) · Nephrology (renal wasting/refractory/complex) · GI (diarrhea/malabsorption) · ICU (arrhythmia, severe/critical) · Addiction/Psychiatry (alcohol use disorder)

– Check the WHOLE panel and the ECG first — one abnormal electrolyte in these patients means the others are likely off too; arrhythmia risk drives urgency
– REPLETE MAGNESIUM FIRST/ALONGSIDE (the linchpin): hypomagnesemia causes ongoing renal K wasting and impairs PTH → makes hypoK and hypoCa refractory; magnesium sulfate 1–2 g IV (more if low), given slowly
– Replete potassium: KCl PO 40–80 mEq/day divided (mild–moderate) or IV ≤10 mEq/h peripheral / ≤20 mEq/h central with monitoring (severe/symptomatic); in saline not dextrose
– Replete phosphate: oral phosphate (mild) or IV sodium/potassium phosphate (severe/symptomatic, e.g. 15–30 mmol over 4–6 h, slowly) — use potassium phosphate to address K and Phos together when both low
– Replete calcium (after/with Mg): oral calcium + vitamin D (mild) or calcium gluconate 1–2 g IV (symptomatic/severe) — but Ca won't correct until Mg is replaced; avoid large Ca into high phosphate
– Replete/correct sodium and acid-base per the specific disturbance (slow Na correction limits apply — ≤8 mEq/L/24h if chronic hyponatremia)
– Refeeding caution: high-risk (alcohol, severe malnutrition, prolonged NPO) → thiamine first, start nutrition low + advance slowly, check Phos/K/Mg before and serially, hold advancement if they fall
– Treat the cause + stop ongoing losses: control diarrhea, adjust/stop diuretics and laxatives, nutrition, alcohol cessation, treat sepsis/critical illness, replace ongoing GI losses
– These never travel alone. When one electrolyte is low in a diarrheal, alcoholic, malnourished, or critically ill patient, check and replace the whole set — and fix the magnesium first, because the potassium and calcium will stay stubbornly low until you do. Then watch for refeeding crashing all of them again once you start feeding.
– PT/OT: fall precautions; mobilize as able; monitor weakness/respiratory status
– Trend: full panel (frequent during active repletion), ECG/QT, renal function, glucose, respiratory status, ongoing losses, response to repletion
– Escalation triggers: arrhythmia/torsades, seizures, respiratory failure, or refractory derangements → ICU + aggressive monitored repletion; refeeding crash → slow feeds + replete; renal wasting/refractory → nephrology
– Discharge checklist: full panel normalized + stable; cause addressed (diarrhea, diuretics/laxatives, nutrition, alcohol support); oral maintenance for ongoing losses; refeeding-safe nutrition plan; outpatient electrolyte recheck + multidisciplinary follow-up; return precautions (palpitations, weakness, cramps, confusion)

111. Mixed Electrolyte Disorders

complete reference · severe diarrhea + malnutrition + alcoholism + critical illness · low K + low Mg + low Phos · magnesium-first co-repletion · Full Card

Symptoms / Associated Sx

• A composite of the individual deficits: weakness, cramps, arrhythmias (QT prolongation, ectopy, torsades), tetany and paresthesias, confusion and seizures, ileus, and failure to wean from the ventilator

• Features of the precipitating illness (volume depletion, malnutrition, alcohol withdrawal)

• The danger is additive — combined hypokalemia, hypomagnesemia, and hypocalcemia is far more arrhythmogenic than any one alone — so when one electrolyte is off, suspect the whole panel is

Neg

• Pt denies that only the most obvious abnormality was measured — the full panel (potassium, magnesium, phosphate, calcium, sodium) must be checked

• Pt denies repletion of potassium and calcium without magnesium, which leaves them refractory

• Pt denies aggressive refeeding before repletion and denies an overlooked, often-coexisting acid-base disturbance

Social History (SHx)

• Severe or chronic diarrhea, or laxative misuse

• Malnutrition, refeeding, and anorexia nervosa

• Alcohol use disorder (poor intake plus losses plus shifts — the prototype)

• Critical illness/sepsis, prolonged NPO status, diuretics, short-gut/malabsorption, and DKA treatment

Main Etiology

• Shared mechanisms strike several electrolytes simultaneously

• GI loss: diarrhea depletes potassium, magnesium, and bicarbonate; vomiting depletes potassium and chloride and generates alkalosis

• Poor intake with depleted stores: malnutrition and alcohol use

• Renal wasting: diuretics, alcohol, and hypomagnesemia driving potassium and calcium loss

• Transcellular shifts: refeeding and insulin drive phosphate, potassium, and magnesium into cells

• Hypomagnesemia as the linchpin, perpetuating refractory hypokalemia and hypocalcemia

RF

• Modifiable: alcohol use, nutrition status, diuretic/laxative use, control of diarrhea

• Non-modifiable: critical illness, malabsorptive states

Data

• Full electrolyte panel: sodium, potassium, magnesium, phosphate, calcium (corrected/ionized), and bicarbonate/BMP

• ECG (QT prolongation, U waves, ectopy — arrhythmia risk)

• Acid-base status (VBG; mixed metabolic disturbances are common)

• Renal function; glucose and ketones (DKA, refeeding); albumin (for calcium correction)

• In refeeding-risk patients, check the panel before feeding and serially; identify and quantify ongoing losses

DDx

Diarrheal losses (low potassium and magnesium, non-gap acidosis) · alcohol/malnutrition (low potassium, magnesium, phosphate, calcium; thiamine deficiency) · refeeding (falling phosphate, potassium, magnesium with feeding) · critical illness (multifactorial) · diuretic effect (low potassium and magnesium with alkalosis)

Home Meds

• Review/hold: diuretics, laxatives, and PPIs (which lower magnesium)

• Support: alcohol cessation; advance nutrition cautiously given refeeding risk

• Renally dose and reconcile all contributing medications

Plan

CONSULT: Nutrition/Dietitian (refeeding, malnutrition) · Nephrology (renal wasting, refractory or complex cases) · GI (diarrhea/malabsorption) · ICU (arrhythmia, severe or critical illness) · Addiction/Psychiatry (alcohol use disorder)

• Check the whole panel and the ECG first: one abnormal electrolyte in these patients means the others are likely deranged too, and the arrhythmia risk drives the urgency

• Replete magnesium first or alongside (the linchpin): hypomagnesemia causes ongoing renal potassium wasting and impairs PTH, making hypokalemia and hypocalcemia refractory — give magnesium sulfate 1–2 g IV (more if markedly low), slowly

• Replete potassium: KCl PO 40–80 mEq/day in divided doses for mild-to-moderate deficits, or IV at ≤10 mEq/h peripherally / ≤20 mEq/h centrally with monitoring for severe or symptomatic cases, mixed in saline rather than dextrose

• Replete phosphate: oral phosphate for mild cases or IV sodium/potassium phosphate for severe or symptomatic cases (e.g. 15–30 mmol over 4–6 hours, slowly), using potassium phosphate to address potassium and phosphate together when both are low

• Replete calcium (after or with magnesium): oral calcium with vitamin D for mild cases, or calcium gluconate 1–2 g IV for symptomatic or severe hypocalcemia — but calcium will not correct until magnesium is replaced, and large calcium loads into a high phosphate should be avoided

• Replete and correct sodium and the acid-base status according to the specific disturbance, observing slow sodium-correction limits (≤8 mEq/L/24h in chronic hyponatremia)

• Refeeding caution: in high-risk patients (alcohol use, severe malnutrition, prolonged NPO) give thiamine first, start nutrition low and advance slowly, check phosphate, potassium, and magnesium before and serially, and hold advancement if they fall

• Treat the cause and stop ongoing losses: control diarrhea, adjust or stop diuretics and laxatives, optimize nutrition, support alcohol cessation, treat sepsis/critical illness, and replace ongoing GI losses

• PT/OT: fall precautions; mobilize as able while monitoring weakness and respiratory status

• Trend: the full panel (frequently during active repletion), the ECG/QT, renal function, glucose, respiratory status, ongoing losses, and the response to repletion

• Escalation triggers: arrhythmia or torsades, seizures, respiratory failure, or refractory derangements → ICU with aggressive monitored repletion; an electrolyte crash during refeeding → slow feeds and replete; renal wasting or refractory cases → nephrology

• Discharge checklist: the full panel normalized and stable; the cause addressed (diarrhea, diuretics/laxatives, nutrition, alcohol support); oral maintenance for ongoing losses; a refeeding-safe nutrition plan; an outpatient electrolyte recheck with multidisciplinary follow-up; return precautions for palpitations, weakness, cramps, or confusion

Red Flags

• Arrhythmia or torsades from combined hypokalemia, hypomagnesemia, and hypocalcemia → ICU and aggressive monitored repletion

• Refractory potassium or calcium despite repletion → unrecognized hypomagnesemia driving both

• Refeeding in a high-risk patient → a simultaneous crash in phosphate, potassium, and magnesium

• Respiratory failure from severe hypophosphatemia in a malnourished patient → ICU

• Coexisting severe acid-base disturbance → reassess with formal acid-base analysis

Senior IM Resident Pearls

• These derangements never travel alone. One low electrolyte in a diarrheal, alcoholic, malnourished, or critically ill patient should prompt checking and repleting the entire set.

• Fix the magnesium first. Potassium and calcium stay stubbornly low until the magnesium is corrected — it's the single most common reason "nothing is working."

• One infusion can fix two problems. Potassium phosphate replaces potassium and phosphate together when both are low — efficient and elegant.

• Anticipate the refeeding crash. Starting nutrition in a depleted patient drives phosphate, potassium, and magnesium back into cells — feed low and slow with thiamine, and recheck.

• Don't forget the acid-base picture. Diarrhea brings a non-gap acidosis, vomiting and diuretics bring an alkalosis — the electrolytes and the pH tell a coherent story.

• Thiamine before glucose in every alcoholic or severely malnourished patient — a cheap step that prevents Wernicke encephalopathy.

• Common mistake: treating the one flagged value and discharging — the unmeasured, untreated companions (especially magnesium) bounce the patient back.

Acid-Base — Metabolic Alkalosis

112. Severe Metabolic Alkalosis

high bicarb + high pH · vomiting / NG suction / diuretics · the urine chloride splits it: saline-responsive vs saline-resistant · replace Cl, volume, and K · Super Compact

Sx: often the underlying process (vomiting, volume depletion) dominates · severe (pH >7.55–7.6): neuromuscular irritability, paresthesias, tetany, ↓ionized Ca effect, confusion/lethargy, seizures, arrhythmia, compensatory hypoventilation (hypercapnia → hypoxemia) · signs of volume depletion · (accompanying hypokalemia and hypochloremia drive much of the morbidity and the arrhythmia risk)

Neg: denies that the K and Cl are unaddressed (alkalosis is maintained by Cl/K/volume depletion — must replace) · denies mixed disorder unexamined (compensation/delta-delta) · denies mineralocorticoid excess overlooked if saline-resistant + hypertensive · denies surreptitious vomiting/diuretic use missed

SHx: vomiting (gastric H⁺/Cl⁻ loss) · NG suction · diuretics (loop/thiazide) · antacid/alkali ingestion (milk-alkali) · hypokalemia · primary hyperaldosteronism/Cushing/licorice (mineralocorticoid excess) · Bartter/Gitelman · cystic fibrosis (Cl loss in sweat)

Etiology: generation + maintenance of high bicarbonate · chloride-responsive (urine Cl <20 — the common ones): vomiting, NG suction, diuretics (after they stop), volume/Cl depletion, post-hypercapnia · chloride-resistant (urine Cl >20): mineralocorticoid excess (primary hyperaldosteronism, Cushing, licorice), severe K depletion, Bartter/Gitelman · maintained by volume depletion, Cl depletion, hypokalemia, and hyperaldosteronism (which sustain renal bicarbonate reabsorption)

RF: protracted vomiting · prolonged NG suction without replacement · aggressive diuresis · hypokalemia · mineralocorticoid excess states

Data: ABG/VBG + BMP (↑HCO3, ↑pH; ↓Cl, ↓K common) · URINE CHLORIDE — the key test (<20 = chloride/saline-responsive [vomiting, NG, diuretic, volume depletion]; >20 = chloride-resistant [mineralocorticoid excess, K depletion]) · Winter's-equivalent compensation check (expected pCO2 ≈ 0.7×HCO3 + 21, or rises ~0.7 per 1 HCO3) (adequate respiratory compensation vs added respiratory disorder) · K, Mg, ionized Ca · volume status · BP (HTN → mineralocorticoid) · consider aldosterone/renin if resistant

DDx: vomiting/NG (urine Cl <20, hypoCl/hypoK) · diuretic (urine Cl variable — high while active, low after) · mineralocorticoid excess (urine Cl >20, HTN, ↓K) · Bartter/Gitelman (resistant, normotensive, renal wasting) · milk-alkali (alkali + ↑Ca + AKI)

Home Meds: review/hold diuretics (loop/thiazide) · stop excess alkali/antacids · replace NG losses · address surreptitious vomiting/diuretic misuse · renally dose

Plan

CONSULT: Nephrology (severe/resistant/refractory, mineralocorticoid workup) · Endocrine (hyperaldosteronism/Cushing) · ICU (severe — pH >7.6, arrhythmia, hypoventilation) · GI (NG management)

– Step 1 — classify with the urine chloride (saline-responsive <20 vs saline-resistant >20) — this dictates treatment
– Saline/chloride-responsive (vomiting, NG, diuretics, volume depletion):
  • IV isotonic saline (0.9% NaCl) — restores volume and chloride, the core treatment; corrects the "contraction" and allows the kidney to excrete bicarbonate
  • Replace potassium (KCl) — hypokalemia maintains the alkalosis; replete (and magnesium — refractory hypoK without it); use KCl, not other K salts, to provide chloride
  • Stop/reduce the cause — hold diuretics, treat vomiting (antiemetics), minimize/replace NG losses
  • For ongoing NG suction: consider an H2 blocker or PPI (reduce gastric acid loss) + replace fluid/Cl/K
– Saline-resistant (mineralocorticoid excess, severe K depletion): saline won't fix it — treat the cause (MRA — spironolactone/eplerenone for hyperaldosteronism; correct severe hypokalemia; workup/treat Cushing, Bartter/Gitelman); endocrine/nephrology
– Adjuncts for severe/refractory: acetazolamide (promotes renal bicarbonate excretion — useful in volume-overloaded/CHF patients who can't take saline, or diuretic-associated); rarely isotonic HCl or hemodialysis with low-bicarbonate bath for life-threatening alkalemia (pH >7.55–7.6 with complications)
– Replace magnesium (co-depleted; needed for K correction)
– The urine chloride is the whole game: low means give saline and chloride (vomiting, NG, diuretics), high means saline won't work and you're looking at mineralocorticoid excess or profound potassium depletion. And remember the alkalosis is maintained by the very things you must replace — chloride, volume, and potassium.
– PT/OT: per underlying illness
– Trend: ABG/VBG + bicarbonate, K, Cl, Mg, ionized Ca, volume status, urine chloride, respiratory status, BP
– Escalation triggers: pH >7.6, arrhythmia, tetany/seizures, or dangerous hypoventilation → ICU; refractory/saline-resistant → nephrology/endocrine + acetazolamide/HCl/dialysis as indicated
– Discharge checklist: bicarbonate/pH normalized + cause addressed (vomiting/NG resolved, diuretics adjusted, mineralocorticoid cause treated); K/Cl/Mg repleted + maintenance if ongoing losses; offending agents reviewed; outpatient electrolyte recheck + relevant follow-up; return precautions (vomiting, weakness, palpitations, confusion, tingling/spasm)

112. Severe Metabolic Alkalosis

complete reference · vomiting + NG suction + diuretic use · urine chloride classification · chloride/volume/potassium repletion · Full Card

Symptoms / Associated Sx

• The underlying process (vomiting, volume depletion) often dominates the picture

• Severe alkalemia (pH >7.55–7.6) causes neuromuscular irritability, paresthesias, tetany (from a reduced ionized calcium effect), confusion, lethargy, seizures, and arrhythmia, with compensatory hypoventilation producing hypercapnia and hypoxemia

• Signs of volume depletion

• Accompanying hypokalemia and hypochloremia drive much of the morbidity and the arrhythmia risk

Neg

• Pt denies unaddressed potassium and chloride — the alkalosis is maintained by chloride, potassium, and volume depletion, which must be replaced

• Pt denies an unexamined mixed disorder (check compensation and the delta-delta)

• Pt denies overlooked mineralocorticoid excess in a saline-resistant, hypertensive patient, and denies missed surreptitious vomiting or diuretic use

Social History (SHx)

• Vomiting (loss of gastric hydrogen and chloride)

• NG suction

• Diuretics (loop and thiazide)

• Antacid or alkali ingestion (milk-alkali syndrome), hypokalemia, mineralocorticoid excess (primary hyperaldosteronism, Cushing, licorice), Bartter/Gitelman syndromes, and cystic fibrosis (chloride loss in sweat)

Main Etiology

• Both generation and maintenance of an elevated bicarbonate

• Chloride-responsive (urine chloride <20 — the common causes): vomiting, NG suction, diuretics (after they have stopped), volume and chloride depletion, and post-hypercapnia

• Chloride-resistant (urine chloride >20): mineralocorticoid excess (primary hyperaldosteronism, Cushing, licorice), severe potassium depletion, and Bartter/Gitelman syndromes

• Maintained by volume depletion, chloride depletion, hypokalemia, and hyperaldosteronism, which together sustain renal bicarbonate reabsorption

RF

• Modifiable: protracted vomiting, unreplaced NG suction, aggressive diuresis, potassium depletion

• Non-modifiable: mineralocorticoid-excess states and tubular disorders

Data

• ABG/VBG with BMP (elevated bicarbonate and pH; low chloride and potassium are common)

• Urine chloride — the key test (<20 indicates chloride/saline-responsive alkalosis from vomiting, NG suction, diuretics, or volume depletion; >20 indicates chloride-resistant alkalosis from mineralocorticoid excess or potassium depletion)

• Respiratory compensation check (the pCO2 should rise ~0.7 mmHg per 1 mEq/L rise in bicarbonate; a value outside the expected range indicates an added respiratory disorder)

• Potassium, magnesium, and ionized calcium; volume status

• Blood pressure (hypertension suggests mineralocorticoid excess); aldosterone/renin if the alkalosis is chloride-resistant

DDx

Vomiting or NG suction (urine chloride <20, hypochloremia, hypokalemia) · diuretics (urine chloride high while active, low after they stop) · mineralocorticoid excess (urine chloride >20, hypertension, hypokalemia) · Bartter/Gitelman (chloride-resistant, normotensive, renal wasting) · milk-alkali (alkali ingestion with hypercalcemia and AKI)

Home Meds

• Review/hold: diuretics (loop/thiazide)

• Stop: excess alkali/antacids; replace NG losses

• Address surreptitious vomiting or diuretic misuse; renally dose medications

Plan

CONSULT: Nephrology (severe, resistant, or refractory cases; mineralocorticoid workup) · Endocrinology (hyperaldosteronism, Cushing) · ICU (severe — pH >7.6, arrhythmia, hypoventilation) · GI (NG management)

• Step 1 — classify with the urine chloride: saline-responsive (<20) versus saline-resistant (>20), which dictates treatment

• Saline/chloride-responsive (vomiting, NG suction, diuretics, volume depletion):

• • IV isotonic saline (0.9% NaCl) restores volume and chloride — the core treatment — correcting the contraction and allowing the kidney to excrete bicarbonate

• • Replace potassium with KCl — hypokalemia maintains the alkalosis, so replete it (with magnesium, since hypokalemia is refractory without it), using KCl to also provide chloride

• • Stop or reduce the cause — hold diuretics, treat vomiting with antiemetics, and minimize or replace NG losses

• • For ongoing NG suction, consider an H2 blocker or PPI to reduce gastric acid loss, with replacement of fluid, chloride, and potassium

• Saline-resistant (mineralocorticoid excess, severe potassium depletion): saline will not correct it — treat the cause (an MRA such as spironolactone or eplerenone for hyperaldosteronism; correction of severe hypokalemia; workup and treatment of Cushing or Bartter/Gitelman), with endocrine/nephrology input

• Adjuncts for severe/refractory alkalosis: acetazolamide promotes renal bicarbonate excretion and is useful in volume-overloaded or heart-failure patients who cannot tolerate saline, or in diuretic-associated alkalosis; rarely, isotonic HCl or hemodialysis with a low-bicarbonate bath is used for life-threatening alkalemia (pH >7.55–7.6 with complications)

• Replace magnesium (co-depleted and needed for potassium correction)

• PT/OT: guided by the underlying illness

• Trend: ABG/VBG with bicarbonate, potassium, chloride, magnesium, ionized calcium, volume status, urine chloride, respiratory status, and blood pressure

• Escalation triggers: pH >7.6, arrhythmia, tetany or seizures, or dangerous hypoventilation → ICU; refractory or saline-resistant cases → nephrology/endocrine with acetazolamide, HCl, or dialysis as indicated

• Discharge checklist: bicarbonate and pH normalized with the cause addressed (vomiting/NG resolved, diuretics adjusted, a mineralocorticoid cause treated); potassium, chloride, and magnesium repleted with maintenance for ongoing losses; offending agents reviewed; an outpatient electrolyte recheck with relevant follow-up; return precautions for vomiting, weakness, palpitations, confusion, or tingling/spasm

Red Flags

• pH >7.6 with arrhythmia, tetany, or seizures → ICU and aggressive correction

• Dangerous compensatory hypoventilation causing hypoxemia → respiratory support

• Saline-resistant alkalosis with hypertension → mineralocorticoid excess workup, as saline will not help

• Refractory hypokalemia maintaining the alkalosis → check and replace magnesium

• Milk-alkali syndrome (alkalosis with hypercalcemia and AKI) → stop the alkali and treat the calcium

Senior IM Resident Pearls

• The urine chloride is the whole game. Low means give saline and chloride (vomiting, NG, diuretics); high means saline won't work and you're looking at mineralocorticoid excess or profound potassium depletion.

• The alkalosis is maintained by what you must replace. Chloride, volume, and potassium depletion sustain the high bicarbonate — replace all three rather than chasing the bicarbonate directly.

• Use KCl, not other potassium salts. The chloride is therapeutic in its own right, correcting the hypochloremia that maintains the alkalosis.

• Acetazolamide is the tool when you can't give saline. In a volume-overloaded or heart-failure patient with a diuretic-associated alkalosis, it promotes bicarbonate excretion without a fluid load.

• Vomiting loses acid in the vomitus but potassium in the urine. The hypokalemia is driven renally by the alkalosis and volume depletion — which is why restoring volume and chloride fixes both.

• Hypertension with hypokalemic alkalosis should prompt a thought of primary hyperaldosteronism rather than reflexive saline.

• Common mistake: giving saline to a saline-resistant alkalosis and expecting it to work — check the urine chloride before committing to a strategy.

Electrolytes — Magnesium

113. Hypermagnesemia

high magnesium · ESRD / excess Mg-containing meds · loss of reflexes → respiratory depression → cardiac arrest as it climbs · IV calcium is the antidote · stop the source, dialyze · Super Compact

Sx: severity tracks the level — mild: nausea, flushing, headache, lethargy · moderate (loss of deep tendon reflexes is an early warning sign): hyporeflexia, somnolence, hypotension, bradycardia · severe (high levels): respiratory muscle paralysis/respiratory depression, complete heart block, hypotension, cardiac arrest · (reflexes disappear before respiratory/cardiac collapse — losing the patellar reflex is the bedside alarm)

Neg: denies normal renal function with no exogenous source (true hypermagnesemia is hard without impaired excretion or a load) · denies missed Mg-containing source (laxatives/antacids/enemas, IV MgSO4, eclampsia treatment) · denies coexisting hyperK/uremia in ESRD unaddressed

SHx: ESRD/CKD/AKI (impaired excretion — the key setup) · Mg-containing laxatives/antacids (milk of magnesia, Maalox), enemas, supplements · IV magnesium therapy (eclampsia/preeclampsia, asthma, arrhythmia) · tumor lysis/rhabdomyolysis (cell release) · lithium · adrenal insufficiency

Etiology: impaired renal excretion (the prerequisite for most cases) — ESRD/CKD/AKI · increased intake/load, especially with renal impairment — Mg-containing laxatives/antacids/enemas, IV MgSO4 (iatrogenic — eclampsia protocols, overshoot), Mg-based bowel preps · cell release — tumor lysis, rhabdomyolysis, hemolysis · rarely adrenal insufficiency, lithium, hypothyroidism

RF: ESRD/CKD/AKI · use of Mg laxatives/antacids in renal impairment · IV magnesium therapy (obstetric) · bowel prep with Mg agents · elderly with constipation on Mg laxatives

Data: serum magnesium (confirm + grade severity) · renal function (BMP) (the context) · ECG (bradycardia, prolonged PR/QRS/QT, heart block, asystole at high levels) · calcium (may need calcium antidote; hypocalcemia worsens toxicity) · K (often coexisting hyperK in ESRD) · deep tendon reflexes (bedside marker of severity) · medication/source review

DDx: renal failure + Mg load (ESRD on Mg laxative — classic) · iatrogenic IV Mg overshoot (obstetric/therapeutic) · cell release (tumor lysis, rhabdo) · exogenous load with normal kidneys (massive ingestion/enema)

Home Meds: STOP all magnesium-containing laxatives, antacids, enemas, supplements (milk of magnesia, Maalox, Mg citrate, MgO) · review IV Mg orders · renally dose everything · avoid Mg bowel preps in renal impairment

Plan

CONSULT: Nephrology (ESRD/renal failure, dialysis, severe) · ICU (respiratory depression, heart block, hemodynamic instability) · Cardiology (heart block/arrhythmia) · OB (if eclampsia-related)

– FIRST — STOP the magnesium source immediately (all Mg laxatives/antacids/enemas/supplements; stop or reduce IV MgSO4) — often sufficient alone if renal function is adequate
– STEP 1 — IV calcium (the antidote) for significant symptoms/ECG changes: calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 min (or calcium chloride via central line) — directly antagonizes magnesium's neuromuscular/cardiac effects; repeat as needed for recurrent symptoms (effect is temporary); for respiratory depression, heart block, severe hypotension
– STEP 2 — enhance elimination:
  • If renal function adequate: IV isotonic saline + loop diuretic (furosemide) to promote renal magnesium excretion (ensure volume)
  • If renal failure/ESRD or severe/refractory: HEMODIALYSIS — definitive removal; the answer when the kidneys can't excrete (i.e. most significant cases occur in ESRD)
– STEP 3 — supportive care: respiratory support/intubation for respiratory muscle paralysis; cardiac monitoring + pacing for symptomatic bradycardia/heart block; treat hypotension; treat coexisting hyperkalemia in ESRD (full cocktail — calcium gluconate 1–2 g IV if ECG changes, insulin 10 u + D50 25 g, albuterol, binder/dialysis)
– Monitor deep tendon reflexes as a bedside gauge — their loss precedes respiratory/cardiac toxicity, their return signals improvement
– Almost every meaningful case is a patient with kidney failure who got a magnesium-containing laxative or antacid — so the first move is to stop the source. IV calcium is the immediate antidote that buys time, but if the kidneys can't clear the magnesium, dialysis is the definitive fix. Watch the reflexes: losing them is the early alarm before breathing and the heart fail.
– PT/OT: as tolerated once stable
– Trend: serial magnesium, ECG, reflexes, respiratory status, BP/HR, renal function, calcium, potassium, dialysis response
– Escalation triggers: respiratory depression, heart block, or hemodynamic instability → ICU + IV calcium + dialysis + support; ESRD/anuric → urgent dialysis; refractory despite saline/diuretic → dialysis
– Discharge checklist: magnesium normalized + source eliminated; education to avoid Mg-containing OTC products in renal impairment (critical for prevention); medication list cleaned of Mg agents; renal/dialysis plan optimized; outpatient Mg recheck + nephrology follow-up; return precautions (weakness, drowsiness, slowed breathing, palpitations/fainting)

113. Hypermagnesemia

complete reference · ESRD + excess magnesium-containing medications · calcium antidote, dialysis, source control · Full Card

Symptoms / Associated Sx

• Severity tracks the level: mild hypermagnesemia causes nausea, flushing, headache, and lethargy

• Moderate hypermagnesemia causes hyporeflexia (loss of deep tendon reflexes is an early warning sign), somnolence, hypotension, and bradycardia

• Severe hypermagnesemia causes respiratory muscle paralysis and respiratory depression, complete heart block, profound hypotension, and cardiac arrest

• Reflexes disappear before respiratory and cardiac collapse — loss of the patellar reflex is the bedside alarm

Neg

• Pt denies normal renal function with no exogenous source — true hypermagnesemia is uncommon without impaired excretion or a magnesium load

• Pt denies a missed magnesium-containing source (laxatives, antacids, enemas, IV magnesium sulfate, eclampsia treatment)

• Pt denies unaddressed coexisting hyperkalemia or uremia in the ESRD setting

Social History (SHx)

• ESRD/CKD/AKI (impaired excretion — the key setup)

• Magnesium-containing laxatives and antacids (milk of magnesia, Maalox), enemas, and supplements

• IV magnesium therapy (for eclampsia/preeclampsia, asthma, or arrhythmia)

• Tumor lysis or rhabdomyolysis (cell release), lithium, and adrenal insufficiency

Main Etiology

• Impaired renal excretion (the prerequisite for most cases): ESRD, CKD, and AKI

• Increased intake or load, especially with renal impairment: magnesium-containing laxatives, antacids, and enemas; IV magnesium sulfate (iatrogenic — eclampsia protocols or overshoot); and magnesium-based bowel preparations

• Cell release: tumor lysis, rhabdomyolysis, and hemolysis

• Rarely adrenal insufficiency, lithium, and hypothyroidism

RF

• Modifiable: use of magnesium laxatives/antacids in renal impairment, magnesium-based bowel preps, and IV magnesium dosing

• Non-modifiable: ESRD/CKD/AKI and cell-release states

Data

• Serum magnesium (confirm and grade severity)

• Renal function (BMP) (the essential context)

• ECG (bradycardia, prolonged PR/QRS/QT, heart block, and asystole at high levels)

• Calcium (may guide the calcium antidote; hypocalcemia worsens toxicity)

• Potassium (coexisting hyperkalemia is common in ESRD)

• Deep tendon reflexes (a bedside marker of severity); medication and source review

DDx

Renal failure with a magnesium load (ESRD on a magnesium laxative — the classic scenario) · iatrogenic IV magnesium overshoot (obstetric or therapeutic) · cell release (tumor lysis, rhabdomyolysis) · exogenous load with normal kidneys (massive ingestion or enema)

Home Meds

• Stop all magnesium-containing products: laxatives, antacids, enemas, and supplements (milk of magnesia, Maalox, magnesium citrate, magnesium oxide)

• Review: IV magnesium orders

• Renally dose all medications and avoid magnesium bowel preps in renal impairment

Plan

CONSULT: Nephrology (ESRD/renal failure, dialysis, severe cases) · ICU (respiratory depression, heart block, hemodynamic instability) · Cardiology (heart block, arrhythmia) · Obstetrics (eclampsia-related)

• First — stop the magnesium source immediately (all magnesium laxatives, antacids, enemas, and supplements; stop or reduce IV magnesium sulfate), which is often sufficient on its own when renal function is adequate

• Step 1 — IV calcium (the antidote) for significant symptoms or ECG changes: calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 minutes (or calcium chloride through a central line), which directly antagonizes magnesium's neuromuscular and cardiac effects and is repeated as needed for recurrent symptoms (since the effect is temporary) — for respiratory depression, heart block, or severe hypotension

• Step 2 — enhance elimination:

• • If renal function is adequate: IV isotonic saline with a loop diuretic (furosemide) to promote renal magnesium excretion, ensuring adequate volume

• • If there is renal failure/ESRD or severe/refractory hypermagnesemia: hemodialysis for definitive removal — the answer when the kidneys cannot excrete (which is the case in most significant episodes, occurring in ESRD)

• Step 3 — supportive care: respiratory support or intubation for respiratory muscle paralysis; cardiac monitoring with pacing for symptomatic bradycardia or heart block; treatment of hypotension; and treatment of coexisting hyperkalemia in ESRD (the full cocktail — calcium gluconate 1–2 g IV if there are ECG changes, insulin 10 units IV with D50 25 g, nebulized albuterol, and a binder or dialysis)

• Monitor deep tendon reflexes as a bedside gauge — their loss precedes respiratory and cardiac toxicity, and their return signals improvement

• PT/OT: as tolerated once stable

• Trend: serial magnesium, the ECG, reflexes, respiratory status, blood pressure and heart rate, renal function, calcium, potassium, and the dialysis response

• Escalation triggers: respiratory depression, heart block, or hemodynamic instability → ICU with IV calcium, dialysis, and support; an ESRD or anuric state → urgent dialysis; refractory despite saline and a diuretic → dialysis

• Discharge checklist: magnesium normalized with the source eliminated; education to avoid magnesium-containing OTC products in renal impairment (critical for prevention); a medication list cleaned of magnesium agents; an optimized renal/dialysis plan; an outpatient magnesium recheck with nephrology follow-up; return precautions for weakness, drowsiness, slowed breathing, or palpitations/fainting

Red Flags

• Respiratory muscle paralysis or respiratory depression → IV calcium, airway support, and dialysis

• Complete heart block, severe bradycardia, or hypotension → IV calcium, pacing, and ICU care

• Loss of deep tendon reflexes → an early warning of impending respiratory and cardiac toxicity

• ESRD or anuric patient with a magnesium load → urgent hemodialysis, as the kidneys cannot clear it

• Coexisting hyperkalemia in ESRD → additive cardiac risk requiring simultaneous treatment

Senior IM Resident Pearls

• It's almost always a renal-failure patient who got a magnesium product. The first and most important move is to stop the magnesium-containing laxative, antacid, or enema.

• IV calcium is the immediate antidote. It antagonizes magnesium's cardiac and neuromuscular effects to buy time, but it's temporary — repeat it and arrange definitive removal.

• If the kidneys can't clear it, dialyze. In ESRD or anuric patients, saline and diuretics won't work — hemodialysis is the definitive treatment.

• The reflexes are your bedside monitor. Hyporeflexia precedes respiratory and cardiac toxicity, so a disappearing patellar reflex is an early alarm; their return tracks recovery.

• Beware the eclampsia overshoot. Therapeutic IV magnesium can climb into the toxic range — monitor reflexes and levels, and keep calcium gluconate at the bedside.

• Prevention is a medication-reconciliation task. Counsel renal patients to avoid OTC magnesium-containing products — the readmission is entirely preventable.

• Common mistake: ordering a magnesium-based bowel prep or milk of magnesia for a constipated patient with CKD/ESRD — a classic iatrogenic cause.

Oncologic / Metabolic Emergency

114. Tumor Lysis Syndrome

massive tumor cell lysis → hyperK + hyperPhos + hyperuricemia + hypoCa + AKI · high-grade lymphoma/leukemia, post-chemo · prevention is everything: hydrate, rasburicase/allopurinol, monitor · Super Compact

Sx: from the metabolic derangements — hyperkalemia (weakness, arrhythmia, arrest), hyperphosphatemia → hypocalcemia (tetany, paresthesias, seizures, ↑QT/arrhythmia), hyperuricemia + AKI (oliguria, edema, uremia), nausea/vomiting, lethargy/confusion · often within 12–72h of starting chemotherapy (or spontaneously in bulky disease) (the cardiac risk from hyperK + hypoCa is the immediate killer; AKI compounds everything)

Neg: denies that prophylaxis was skipped in a high-risk patient (prevention >> treatment) · denies missed AKI/oliguria · denies that calcium is being given aggressively into high phosphate (precipitation) · denies G6PD status unchecked before rasburicase (hemolysis risk) · denies urine alkalinization being used (no longer recommended)

SHx: high tumor burden / rapidly proliferating malignancy — acute leukemias (esp ALL, AML with high WBC), high-grade lymphomas (Burkitt), bulky disease, high LDH · recent/initiating cytotoxic chemotherapy (or steroids, radiation); pre-existing CKD/volume depletion (↑risk); G6PD deficiency history

Etiology: rapid release of intracellular contents from lysing tumor cells overwhelms clearance → ↑K, ↑phosphate (→ binds calcium → ↓Ca + CaPO4 precipitation in kidneys), ↑uric acid (purine breakdown → uric acid crystals in tubules) → AKI · triggered by chemotherapy in chemosensitive bulky tumors, sometimes spontaneous · AKI then worsens all the derangements (impaired excretion)

RF: bulky/high-grade hematologic malignancy (Burkitt, ALL, high-WBC AML) · high LDH/uric acid pre-treatment · pre-existing CKD or volume depletion · nephrotoxin exposure · initiation of effective chemotherapy

Data — define + monitor (Cairo-Bishop: ≥2 lab abnormalities within 3 days before–7 days after chemo): potassium, phosphate, calcium (corrected/ionized), uric acid, LDH · renal function (Cr/BUN), urine output · ECG (hyperK changes, ↑QT from hypoCa) · frequent serial labs (q4–8h in high-risk during the window) · volume status · consider urinalysis (uric acid crystals)

DDx: TLS (the constellation post-chemo) · isolated hyperkalemia (other causes) · isolated AKI (other causes) · contrast/nephrotoxic AKI · hypercalcemia of malignancy (opposite Ca direction) · sepsis with multiorgan involvement

Home Meds: hold nephrotoxins (NSAIDs, contrast, aminoglycosides) · hold/avoid K and phosphate supplements · review uricosurics · avoid thiazides (uric acid) · renally dose chemo/supportive meds

Plan

CONSULT: Oncology/Hematology (primary — chemo timing, risk) · Nephrology (AKI, dialysis, severe) · ICU (severe/unstable — arrhythmia, refractory) · Pharmacy (rasburicase, G6PD)

– PREVENTION (the core — risk-stratify before chemo):
  • Aggressive IV hydration: isotonic fluids (e.g. ~2.5–3 L/m²/day or weight-based, often 200–300 mL/h) starting 24–48h before and continuing through chemo — maintain high urine output to flush uric acid/phosphate; do NOT routinely alkalinize urine (promotes calcium-phosphate precipitation; not recommended)
  • Hypouricemic therapy: allopurinol (blocks new uric acid formation — for lower/intermediate risk; start before chemo) OR rasburicase (recombinant urate oxidase — degrades existing uric acid; for high risk or established TLS with high uric acid) — CHECK G6PD before rasburicase (contraindicated in G6PD deficiency — causes severe hemolysis + methemoglobinemia)
  • Frequent monitoring (labs q4–8h, ECG, UOP, telemetry) in high-risk during the window
– TREATMENT of established TLS — manage each derangement:
  • Hyperkalemia (most urgent): ECG; if changes → calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 min (cardiac protection — caution in concurrent hypocalcemia/hyperphos but use for ECG changes), insulin 10 units IV + D50 25 g (recheck glucose), albuterol 10–20 mg neb, then removal — loop diuretic if making urine, GI binder (patiromer/SZC), hemodialysis for refractory/severe; continuous monitoring
  • Hyperphosphatemia: IV fluids, phosphate binders; dialysis if severe
  • Hypocalcemia: treat ONLY if symptomatic (tetany, seizure, arrhythmia) with calcium gluconate — giving calcium into high phosphate risks precipitation/worsening AKI; prioritize lowering phosphate; use minimum needed
  • Hyperuricemia: rasburicase (if not G6PD deficient) + hydration
  • AKI / refractory: hemodialysis / CRRT for severe AKI, refractory hyperkalemia, severe hyperphosphatemia, volume overload, or oliguria unresponsive to fluids — clears K, phosphate, and uric acid together
– In tumor lysis the strategy is prevention first: identify the high-risk patient before chemo, hydrate aggressively, and give the right hypouricemic agent — checking G6PD before any rasburicase. Don't alkalinize the urine, and don't pour calcium into a high phosphate. When the kidneys fail or the potassium is refractory, dialysis fixes potassium, phosphate, and uric acid in one go.
– PT/OT: per status
– Trend: K, phosphate, calcium, uric acid, Cr/BUN, UOP, ECG, volume status — frequently through the at-risk window
– Escalation triggers: arrhythmia/refractory hyperK, severe AKI/oliguria, symptomatic hypocalcemia, or volume overload → ICU + dialysis/CRRT; rising uric acid despite allopurinol → rasburicase (check G6PD)
– Discharge checklist: derangements resolved + renal function recovering; chemo/oncology plan coordinated; prophylaxis plan for future cycles documented; nephrotoxins reviewed; outpatient labs + oncology/nephrology follow-up; return precautions (decreased urination, palpitations, cramps/tingling, weakness, confusion)

114. Tumor Lysis Syndrome

complete reference · hyperkalemia + hyperphosphatemia + hypocalcemia + hyperuricemia + AKI · prevention-focused · Full Card

Symptoms / Associated Sx

• Driven by the metabolic derangements: hyperkalemia (weakness, arrhythmia, arrest); hyperphosphatemia causing hypocalcemia (tetany, paresthesias, seizures, QT prolongation, arrhythmia); and hyperuricemia with AKI (oliguria, edema, uremia)

• Nausea, vomiting, lethargy, and confusion

• Onset is typically within 12–72 hours of starting chemotherapy, or spontaneously in bulky disease

• The cardiac risk from combined hyperkalemia and hypocalcemia is the immediate threat, and AKI compounds every derangement

Neg

• Pt denies that prophylaxis was skipped in a high-risk patient — prevention far outweighs treatment

• Pt denies a missed AKI or oliguria, and denies aggressive calcium administration into a high phosphate (precipitation risk)

• Pt denies an unchecked G6PD status before rasburicase (hemolysis risk) and denies the use of urine alkalinization (no longer recommended)

Social History (SHx)

• High tumor burden or rapidly proliferating malignancy — acute leukemias (especially ALL and AML with a high white cell count), high-grade lymphomas (Burkitt), bulky disease, and a high LDH

• Recent or initiating cytotoxic chemotherapy (or steroids, radiation)

• Pre-existing CKD or volume depletion (increased risk); a history of G6PD deficiency

Main Etiology

• Rapid release of intracellular contents from lysing tumor cells overwhelms clearance, producing hyperkalemia, hyperphosphatemia (the phosphate binds calcium, causing hypocalcemia and calcium-phosphate precipitation in the kidneys), and hyperuricemia (purine breakdown forms uric acid crystals in the tubules), culminating in AKI

• Triggered by chemotherapy in chemosensitive bulky tumors, and occasionally spontaneous

• The resulting AKI then worsens all the derangements through impaired excretion

RF

• Modifiable: pre-treatment volume depletion, nephrotoxin exposure, and adequacy of prophylaxis

• Non-modifiable: bulky high-grade hematologic malignancy, a high pre-treatment LDH and uric acid, pre-existing CKD, and the initiation of effective chemotherapy

Data

• By the Cairo-Bishop definition, ≥2 laboratory abnormalities within 3 days before to 7 days after chemotherapy

• Potassium, phosphate, calcium (corrected/ionized), uric acid, and LDH

• Renal function (creatinine, BUN) and urine output

• ECG (hyperkalemic changes and QT prolongation from hypocalcemia)

• Frequent serial labs (every 4–8 hours in high-risk patients during the window); volume status; urinalysis for uric acid crystals if relevant

DDx

Tumor lysis syndrome (the post-chemotherapy constellation) · isolated hyperkalemia (other causes) · isolated AKI (other causes) · contrast or nephrotoxic AKI · hypercalcemia of malignancy (opposite calcium direction) · sepsis with multiorgan involvement

Home Meds

• Hold: nephrotoxins (NSAIDs, contrast, aminoglycosides)

• Hold/avoid: potassium and phosphate supplements; review uricosurics; avoid thiazides (raise uric acid)

• Renally dose chemotherapy and supportive medications

Plan

CONSULT: Oncology/Hematology (primary — chemotherapy timing and risk) · Nephrology (AKI, dialysis, severe cases) · ICU (severe or unstable — arrhythmia, refractory derangements) · Pharmacy (rasburicase, G6PD status)

• Prevention (the core — risk-stratify before chemotherapy):

• • Aggressive IV hydration: isotonic fluids (approximately 2.5–3 L/m²/day or weight-based, often 200–300 mL/h) started 24–48 hours before and continued through chemotherapy to maintain a high urine output that flushes uric acid and phosphate — and do not routinely alkalinize the urine, which promotes calcium-phosphate precipitation and is no longer recommended

• • Hypouricemic therapy: allopurinol (which blocks new uric acid formation, for lower/intermediate risk, started before chemotherapy) or rasburicase (recombinant urate oxidase, which degrades existing uric acid, for high risk or established TLS with a high uric acid) — and check G6PD before rasburicase, which is contraindicated in G6PD deficiency because it causes severe hemolysis and methemoglobinemia

• • Frequent monitoring (labs every 4–8 hours, ECG, urine output, telemetry) in high-risk patients during the window

• Treatment of established TLS — manage each derangement:

• • Hyperkalemia (most urgent): obtain an ECG, and for ECG changes give calcium gluconate 1–2 g IV (10 mL of 10%) over 2–5 minutes for cardiac protection (used for ECG changes despite concurrent hypocalcemia/hyperphosphatemia), insulin 10 units IV with D50 25 g (rechecking glucose), and nebulized albuterol 10–20 mg, followed by removal — a loop diuretic if making urine, a GI binder (patiromer or sodium zirconium cyclosilicate), and hemodialysis for refractory or severe cases — with continuous monitoring

• • Hyperphosphatemia: IV fluids and phosphate binders, with dialysis if severe

• • Hypocalcemia: treat only if symptomatic (tetany, seizure, arrhythmia) with calcium gluconate, because giving calcium into a high phosphate risks precipitation and worsening AKI — prioritize lowering the phosphate and use the minimum calcium needed

• • Hyperuricemia: rasburicase (if not G6PD deficient) with hydration

• • AKI or refractory derangements: hemodialysis or CRRT for severe AKI, refractory hyperkalemia, severe hyperphosphatemia, volume overload, or oliguria unresponsive to fluids — clearing potassium, phosphate, and uric acid together

• PT/OT: guided by clinical status

• Trend: potassium, phosphate, calcium, uric acid, creatinine/BUN, urine output, the ECG, and volume status — frequently through the at-risk window

• Escalation triggers: arrhythmia or refractory hyperkalemia, severe AKI or oliguria, symptomatic hypocalcemia, or volume overload → ICU with dialysis/CRRT; a rising uric acid despite allopurinol → rasburicase (after checking G6PD)

• Discharge checklist: derangements resolved with recovering renal function; a coordinated chemotherapy/oncology plan; a documented prophylaxis plan for future cycles; nephrotoxins reviewed; outpatient labs with oncology/nephrology follow-up; return precautions for decreased urination, palpitations, cramps or tingling, weakness, or confusion

Red Flags

• Hyperkalemia with ECG changes or arrhythmia → emergent calcium and the full cocktail; can progress to arrest

• Symptomatic hypocalcemia (tetany, seizure) with a high phosphate → cautious calcium and urgent phosphate lowering

• Oliguric AKI or volume overload → urgent dialysis/CRRT

• Rasburicase given to a G6PD-deficient patient → severe hemolysis and methemoglobinemia

• Rising uric acid and phosphate despite hydration → escalate hypouricemic therapy and consider dialysis

Senior IM Resident Pearls

• Prevention beats treatment. Identify the high-risk patient (bulky Burkitt, high-WBC leukemia, high LDH) before chemotherapy, hydrate aggressively, and start the right hypouricemic agent — established TLS is far harder to manage.

• Check G6PD before rasburicase. In G6PD deficiency it causes severe hemolysis and methemoglobinemia — a catastrophic, avoidable error.

• Don't alkalinize the urine. Old teaching favored bicarbonate, but it promotes calcium-phosphate precipitation in the tubules and is no longer recommended — hydration is the strategy.

• Don't pour calcium into a high phosphate. Treat hypocalcemia only when symptomatic, with the minimum calcium, because the calcium-phosphate product precipitates in tissues and kidneys.

• Dialysis is the great equalizer. When the kidneys fail or the potassium is refractory, hemodialysis or CRRT clears potassium, phosphate, and uric acid simultaneously.

• Allopurinol prevents, rasburicase rescues. Allopurinol blocks new uric acid formation but doesn't touch what's already there; rasburicase degrades the existing burden — match the agent to the risk and the situation.

• Common mistake: reacting to TLS instead of anticipating it — the highest-yield intervention is pre-chemo risk stratification with hydration and prophylaxis already running.

Endocrine Emergency — Electrolytes

115. Adrenal Crisis — Electrolyte Abnormalities

cortisol ± aldosterone deficiency · the triad: hyponatremia + hyperkalemia + hypoglycemia · refractory hypotension · GIVE STEROIDS EMPIRICALLY — don't wait for cortisol · Super Compact

Sx: refractory hypotension/shock (poorly responsive to fluids and pressors — the hallmark), profound weakness/fatigue, nausea/vomiting/abdominal pain, fever, confusion · the electrolyte triad: hyponatremia + hyperkalemia + hypoglycemia · clues to chronic adrenal insufficiency: hyperpigmentation (primary/Addison), weight loss, salt craving; or recent steroid withdrawal (suspect in any shocked patient who doesn't respond as expected, especially with hypoNa + hyperK + hypoglycemia)

Neg: denies that steroids were withheld pending cortisol (treat empirically — don't delay) · denies missed precipitant (infection/sepsis, MI, surgery, steroid cessation) · denies that this is only being treated as simple hyponatremia/hyperkalemia (the unifying diagnosis is adrenal) · denies unrecognized chronic steroid use/abrupt withdrawal

SHx: known adrenal insufficiency/Addison or on chronic glucocorticoids (abrupt withdrawal/illness without stress dosing — the commonest cause) · pituitary disease/surgery (secondary) · autoimmune disease · precipitant: infection/sepsis, surgery, trauma, MI, missed steroid doses · bilateral adrenal hemorrhage (anticoagulation, sepsis — Waterhouse-Friderichsen), checkpoint-inhibitor therapy

Etiology: acute insufficiency of cortisol (± aldosterone in primary) · primary (adrenal — Addison, hemorrhage, autoimmune): both cortisol + aldosterone lost → hyponatremia + hyperkalemia (aldosterone deficiency — Na wasting, K retention) + hypoglycemia + hypotension · secondary (pituitary/hypothalamic, or steroid withdrawal): cortisol deficiency mainly (aldosterone intact — RAAS-driven) → hyponatremia + hypoglycemia, usually NO hyperkalemia · precipitated by stress (infection, surgery) increasing cortisol demand

RF: chronic glucocorticoid therapy (abrupt stop/illness) · known adrenal insufficiency without stress dosing · pituitary disease · autoimmune/polyglandular syndromes · anticoagulation/sepsis (adrenal hemorrhage) · checkpoint inhibitors

Data: BMP (hyponatremia, hyperkalemia [primary], low bicarbonate) · glucose (hypoglycemia) · cortisol (draw random/AM cortisol BEFORE steroids if it won't delay treatment) + ACTH (low cortisol; high ACTH = primary, low/normal = secondary) · cosyntropin (ACTH) stimulation test (later, after stabilization or with dexamethasone) · ECG (hyperkalemia changes) · cultures/infection workup (precipitant) · renin/aldosterone (primary) · consider adrenal imaging (hemorrhage)

DDx: adrenal crisis (hypoNa + hyperK + hypoglycemia + refractory hypotension) · septic shock (may coexist/precipitate) · SIADH/other hyponatremia (no hyperK/hypoglycemia/hypotension pattern) · hyperkalemia from renal failure (check renal fxn) · hypothyroid/myxedema (overlap)

Home Meds: continue/escalate (stress-dose) glucocorticoids if chronic steroid/adrenal insufficiency · hold ACEi/ARB/K-sparing diuretics (worsen hyperK) · review anticoagulation (hemorrhage) · resume home steroid + mineralocorticoid (fludrocortisone) once stable

Plan

CONSULT: Endocrine (diagnosis, steroid/mineralocorticoid management, stim testing) · ICU (shock/instability) · ID (precipitating infection)

– TREAT EMPIRICALLY — do not wait for cortisol results if adrenal crisis is suspected (delay is fatal); draw cortisol/ACTH first only if it won't delay steroids
– STEP 1 — glucocorticoid (the definitive, life-saving treatment): hydrocortisone 100 mg IV bolus, then 50 mg IV q6h (or 200 mg/24h continuous infusion) — hydrocortisone provides both glucocorticoid and (at stress dose) mineralocorticoid activity; (if the diagnosis is unconfirmed and you want to preserve the stim test, dexamethasone 4 mg IV is an alternative that doesn't cross-react with the cortisol assay — but hydrocortisone is preferred for treatment)
– STEP 2 — aggressive IV fluids + dextrose: isotonic saline (0.9% NaCl) for volume/hypotension and to correct hyponatremia (large volumes often needed); add dextrose (D5) / treat hypoglycemia (D50 if severe) — the saline addresses both the hypovolemia and the hyponatremia
– STEP 3 — manage the electrolytes (often correct with steroids + fluids):
  • Hyponatremia: corrects with isotonic saline + cortisol (cortisol turns off the inappropriate ADH) — watch the correction rate (≤8 mEq/L/24h to avoid osmotic demyelination, especially as it may rise briskly once cortisol given)
  • Hyperkalemia: usually improves with volume + cortisol/mineralocorticoid effect; if severe/ECG changes → stabilize-shift-remove cocktail (calcium gluconate 1–2 g IV if ECG changes, insulin 10 u + D50 25 g, albuterol 10–20 mg neb, then loop/binder/dialysis)
  • Hypoglycemia: dextrose as above; recheck glucose
– STEP 4 — find and treat the precipitant: cultures + empiric antibiotics if infection/sepsis suspected; evaluate for MI, surgery stress, adrenal hemorrhage, steroid noncompliance
– Mineralocorticoid: add fludrocortisone once transitioning off high-dose hydrocortisone (high-dose hydrocortisone itself covers mineralocorticoid needs acutely) — for primary adrenal insufficiency
– The single rule that saves lives here: if you suspect adrenal crisis, give hydrocortisone immediately — draw a cortisol on the way past if it costs no time, but never withhold steroids waiting for the result. The hyponatremia, hyperkalemia, and hypoglycemia are the fingerprint; fluids and cortisol fix most of it, and the stim test can wait until the patient is alive and stable.
– PT/OT: once stable
– Trend: BP/hemodynamics, Na (correction rate), K, glucose (frequent), renal function, ECG, response to steroids, infection markers
– Escalation triggers: refractory shock → ICU + vasopressors + ensure adequate steroids (hypotension responsive to steroids is the clue); severe hyperK/ECG changes → cocktail ± dialysis; overcorrecting Na → slow; ongoing precipitant → treat aggressively
– Discharge checklist: stabilized + transitioned to oral maintenance glucocorticoid (± fludrocortisone for primary); precipitant treated; sick-day rules education + emergency injectable hydrocortisone + medical alert ID (critical to prevent recurrence); endocrine follow-up + stim testing/diagnosis confirmation; electrolytes normalized; return precautions (vomiting, inability to take meds, dizziness/fainting, weakness)

115. Adrenal Crisis — Electrolyte Abnormalities

complete reference · hyponatremia + hyperkalemia + hypoglycemia · empiric hydrocortisone + fluids + dextrose · Full Card

Symptoms / Associated Sx

• Refractory hypotension and shock, poorly responsive to fluids and vasopressors — the hallmark

• Profound weakness and fatigue, nausea, vomiting, abdominal pain, fever, and confusion

• The electrolyte triad of hyponatremia, hyperkalemia, and hypoglycemia

• Clues to chronic adrenal insufficiency: hyperpigmentation (primary/Addison disease), weight loss, and salt craving; or recent steroid withdrawal

• Suspect it in any shocked patient who does not respond as expected, especially with the hyponatremia-hyperkalemia-hypoglycemia pattern

Neg

• Pt denies that steroids were withheld pending the cortisol result — treat empirically without delay

• Pt denies a missed precipitant (infection/sepsis, MI, surgery, steroid cessation)

• Pt denies that the picture is being treated only as isolated hyponatremia or hyperkalemia when the unifying diagnosis is adrenal; and denies unrecognized chronic steroid use with abrupt withdrawal

Social History (SHx)

• Known adrenal insufficiency/Addison disease, or chronic glucocorticoid use with abrupt withdrawal or illness without stress dosing (the most common cause)

• Pituitary disease or surgery (secondary insufficiency); autoimmune disease

• A precipitant — infection/sepsis, surgery, trauma, MI, or missed steroid doses

• Bilateral adrenal hemorrhage (anticoagulation, sepsis — Waterhouse-Friderichsen syndrome); checkpoint-inhibitor therapy

Main Etiology

• Acute insufficiency of cortisol, with or without aldosterone in primary disease

• Primary (adrenal — Addison, hemorrhage, autoimmune): both cortisol and aldosterone are lost, producing hyponatremia and hyperkalemia (aldosterone deficiency causes sodium wasting and potassium retention) along with hypoglycemia and hypotension

• Secondary (pituitary/hypothalamic, or steroid withdrawal): mainly cortisol deficiency with intact aldosterone (RAAS-driven), producing hyponatremia and hypoglycemia but usually no hyperkalemia

• Precipitated by stress (infection, surgery) that increases cortisol demand beyond the limited reserve

RF

• Modifiable: stress-dosing practices, steroid adherence, anticoagulation management

• Non-modifiable: known adrenal insufficiency, pituitary disease, autoimmune/polyglandular syndromes, and checkpoint-inhibitor therapy

Data

• BMP (hyponatremia and hyperkalemia in primary disease, with a low bicarbonate)

• Glucose (hypoglycemia)

• Cortisol (a random or AM cortisol drawn before steroids if it won't delay treatment) and ACTH (low cortisol; a high ACTH indicates primary disease, a low/normal ACTH indicates secondary)

• Cosyntropin (ACTH) stimulation test later, after stabilization or while on dexamethasone

• ECG (hyperkalemic changes); cultures and an infection workup for the precipitant; renin/aldosterone in primary disease; adrenal imaging if hemorrhage is suspected

DDx

Adrenal crisis (hyponatremia, hyperkalemia, hypoglycemia, and refractory hypotension) · septic shock (may coexist with or precipitate it) · SIADH or other hyponatremia (without the hyperkalemia, hypoglycemia, and hypotension pattern) · hyperkalemia from renal failure (check renal function) · hypothyroidism/myxedema (overlapping features)

Home Meds

• Continue/escalate (stress-dose) glucocorticoids in patients on chronic steroids or with known adrenal insufficiency

• Hold: ACE inhibitors/ARBs and potassium-sparing diuretics (which worsen hyperkalemia); review anticoagulation (hemorrhage)

• Resume the home steroid and mineralocorticoid (fludrocortisone) once stable

Plan

CONSULT: Endocrinology (diagnosis, steroid/mineralocorticoid management, stimulation testing) · ICU (shock or instability) · Infectious Disease (precipitating infection)

• Treat empirically — do not wait for the cortisol result if adrenal crisis is suspected, since delay is fatal; draw cortisol and ACTH first only if it will not delay steroids

• Step 1 — glucocorticoid (the definitive, life-saving treatment): hydrocortisone 100 mg IV bolus, then 50 mg IV every 6 hours (or 200 mg/24h as a continuous infusion); hydrocortisone provides both glucocorticoid and, at stress doses, mineralocorticoid activity — and if the diagnosis is unconfirmed and the stimulation test should be preserved, dexamethasone 4 mg IV is an alternative that does not cross-react with the cortisol assay, though hydrocortisone is preferred for treatment

• Step 2 — aggressive IV fluids and dextrose: isotonic saline (0.9% NaCl) for volume and hypotension and to correct the hyponatremia (large volumes are often needed), with added dextrose (D5, or D50 for severe hypoglycemia) — the saline addresses both the hypovolemia and the hyponatremia

• Step 3 — manage the electrolytes (which often correct with steroids and fluids):

• • Hyponatremia: corrects with isotonic saline and cortisol (cortisol switches off the inappropriate ADH) — watch the correction rate (≤8 mEq/L/24h to avoid osmotic demyelination, especially as the sodium may rise briskly once cortisol is given)

• • Hyperkalemia: usually improves with volume and the cortisol/mineralocorticoid effect; if severe or with ECG changes, use the stabilize-shift-remove cocktail (calcium gluconate 1–2 g IV for ECG changes, insulin 10 units IV with D50 25 g, nebulized albuterol 10–20 mg, then a loop diuretic, binder, or dialysis)

• • Hypoglycemia: dextrose as above, with rechecking of the glucose

• Step 4 — find and treat the precipitant: cultures and empiric antibiotics if infection/sepsis is suspected, and evaluation for MI, surgical stress, adrenal hemorrhage, or steroid noncompliance

• Mineralocorticoid: add fludrocortisone when transitioning off high-dose hydrocortisone (high-dose hydrocortisone itself covers mineralocorticoid needs acutely), for primary adrenal insufficiency

• PT/OT: once stable

• Trend: blood pressure and hemodynamics, sodium (correction rate), potassium, glucose (frequently), renal function, the ECG, the response to steroids, and infection markers

• Escalation triggers: refractory shock → ICU with vasopressors and assurance of adequate steroid dosing (hypotension that responds to steroids is itself a diagnostic clue); severe hyperkalemia or ECG changes → the cocktail with possible dialysis; overcorrection of sodium → slow the rate; an ongoing precipitant → treat aggressively

• Discharge checklist: stabilized and transitioned to oral maintenance glucocorticoid (with fludrocortisone for primary disease); the precipitant treated; sick-day rules education with an emergency injectable hydrocortisone kit and a medical-alert ID (critical to prevent recurrence); endocrine follow-up with stimulation testing and diagnostic confirmation; electrolytes normalized; return precautions for vomiting, inability to take medications, dizziness or fainting, or weakness

Red Flags

• Refractory hypotension unresponsive to fluids and pressors → give hydrocortisone immediately; a steroid-responsive shock is the diagnostic clue

• The hyponatremia-hyperkalemia-hypoglycemia triad in a sick patient → adrenal crisis until proven otherwise

• Severe hyperkalemia with ECG changes → emergent calcium and the full cocktail

• Bilateral adrenal hemorrhage (anticoagulation, sepsis) → a rapidly fatal cause requiring imaging and steroids

• Abrupt withdrawal of chronic steroids during illness → a preventable, common precipitant

Senior IM Resident Pearls

• Give hydrocortisone first, ask questions later. If you suspect adrenal crisis, treat empirically — draw a cortisol on the way past if it costs no time, but never withhold steroids waiting for the result.

• The electrolyte triad is the fingerprint. Hyponatremia plus hyperkalemia plus hypoglycemia in a hypotensive patient should trigger the diagnosis even before any hormone result returns.

• Primary loses aldosterone, secondary doesn't. The hyperkalemia points to primary adrenal failure (aldosterone deficiency); secondary insufficiency and steroid withdrawal usually spare the potassium.

• Saline fixes two problems at once — the hypovolemic hypotension and the hyponatremia — but watch the correction rate, as the sodium can rise fast once cortisol is on board.

• Dexamethasone preserves the stim test. If you must treat before confirming the diagnosis, dexamethasone doesn't interfere with the cortisol assay — but hydrocortisone is the better treatment drug.

• Always hunt for the precipitant. Crisis rarely happens without a trigger — infection is the classic one, so culture and cover empirically.

• Common mistake: treating the hyponatremia and hyperkalemia as separate problems and missing the unifying adrenal diagnosis — and the even costlier error of waiting for the cortisol before giving steroids.