Micronutrient Deficiencies in Critical Care

Clinical Overview

Micronutrient deficiencies are common in critically ill patients, with prevalence ranging from 30-80% depending on the micronutrient assessed and patient population. [1,2,3] These deficiencies arise from multiple factors including inadequate intake, increased metabolic demand, redistribution, enhanced losses (renal replacement therapy, diarrhea, surgical drains), and impaired absorption. [4,5]

Despite their low abundance in the body, micronutrients play essential roles as cofactors for enzymatic reactions, antioxidant defense, immune function, wound healing, and metabolic regulation. Deficiencies can significantly impact patient outcomes, including prolonged mechanical ventilation, increased infectious complications, delayed wound healing, and mortality. [6,7,8]

The Australian and New Zealand context presents unique considerations, including TGA (Therapeutic Goods Administration) approval for supplements, PBS (Pharmaceutical Benefits Scheme) coverage, and Indigenous health disparities. Aboriginal and Torres Strait Islander peoples have higher rates of micronutrient deficiencies due to socioeconomic factors, chronic disease burden, and food insecurity. [9,10]

Epidemiology and Risk Factors

Prevalence in Critical Illness

Thiamine (Vitamin B1):

Deficiency in 20-33% of critically ill patients on ICU admission [11,12]
Up to 70% in septic shock patients [13]
Higher prevalence in chronic alcohol use, malnutrition, chronic disease, prolonged diuretic use

Vitamin D (25-Hydroxyvitamin D):

Deficiency (<50 nmol/L or <20 ng/mL) in 40-80% of ICU patients [14,15]
Severe deficiency (<30 nmol/L or <12 ng/mL) in 17-26% [16]
Associated with increased mortality, longer ICU stay, and higher infection rates [17,18]

Vitamin C (Ascorbic Acid):

Depletion to undetectable levels within 24-48 hours of ICU admission in sepsis [19,20]
Hypovitaminosis C (plasma <23 μmol/L) in 38-60% of ICU patients [21]

Selenium:

Deficiency (plasma <70 μg/L) in 40-60% of septic patients [22,23]
Selenoprotein P levels reduced by 30-50% in critical illness [24]

Zinc:

Hypozincemia (plasma <10.7 μmol/L) in 30-40% of ICU patients [25,26]
Redistribution during acute phase response complicates assessment

Other Micronutrients:

Vitamin B12 and folate deficiency: 10-20% in ICU patients, higher in malabsorption, chronic disease [27]
Vitamin K deficiency: 15-30% in ICU patients receiving broad-spectrum antibiotics [28]
Trace element deficiencies (copper, manganese, chromium, molybdenum): Variable, 5-25% depending on element [29,30]

Risk Factors for Micronutrient Deficiencies in ICU

Malnutrition and Chronic Disease
- BMI <18.5 kg/m² or unintentional weight loss >10% in 3-6 months
- Chronic alcohol use (thiamine, folate, B12, zinc)
- Chronic kidney disease (vitamin D, water-soluble vitamins)
- Chronic liver disease (fat-soluble vitamins, zinc)
- Inflammatory bowel disease (iron, folate, B12, fat-soluble vitamins)
Critical Illness Factors
- Sepsis and SIRS (vitamin C, selenium, zinc)
- Burns (selenium, zinc, vitamin C, copper)
- Trauma (thiamine, vitamin C, zinc)
- Major surgery (vitamin C, selenium, zinc)
Iatrogenic Factors
- Prolonged diuretics (thiamine, magnesium, potassium)
- Broad-spectrum antibiotics (vitamin K)
- Renal replacement therapy (water-soluble vitamins, selenium, zinc)
- Prolonged parenteral nutrition without supplementation
Indigenous Australian and Māori Populations
- Higher rates of chronic disease (diabetes, CKD) with associated micronutrient deficiencies [9,10]
- Food insecurity and limited access to fresh produce in remote/rural areas
- Lower vitamin D levels despite sun exposure (skin pigmentation, clothing, indoor occupations) [31]

Pathophysiology

Thiamine (Vitamin B1)

Thiamine is a water-soluble vitamin essential for carbohydrate metabolism, serving as a cofactor for pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase, and transketolase. [32,33]

Mechanism of Deficiency in Critical Illness:

Increased metabolic demand during stress and sepsis (10-20 fold increase in glucose turnover) [11]
Enhanced renal clearance in polyuric states
Redistribution and consumption during acute illness
Inadequate intake (malnutrition, chronic alcohol use)

Clinical Consequences:

Lactic Acidosis: PDH dysfunction prevents pyruvate entry into Krebs cycle, shunting to lactate production ("Type B" lactic acidosis with adequate tissue oxygenation) [34,35]
Wernicke Encephalopathy (WE): Acute neurological syndrome due to thiamine depletion in mammillary bodies, thalamus, and periaqueductal gray matter
- Classic triad (only present in 10-16% of cases): confusion, ataxia, ophthalmoplegia [36]
- Non-alcoholic WE increasingly recognized in ICU (hyperemesis, malnutrition, post-bariatric surgery) [37]
Cardiovascular Dysfunction: Impaired oxidative metabolism in myocardium, high-output cardiac failure ("wet beriberi") [38]
Refeeding Syndrome: Thiamine deficiency exacerbated by dextrose administration, driving intracellular shifts of phosphate, potassium, magnesium [39,40]

Vitamin D (Cholecalciferol and Ergocalciferol)

Vitamin D is a fat-soluble prohormone converted to 25-hydroxyvitamin D [25(OH)D] in the liver, then to active 1,25-dihydroxyvitamin D [1,25(OH)₂D] in the kidneys. [41]

Mechanism of Deficiency in Critical Illness:

Reduced synthesis (limited sun exposure in ICU)
Consumption during acute phase response
Reduced hepatic 25-hydroxylation in liver dysfunction
Enhanced degradation and urinary losses (vitamin D-binding protein lost in proteinuria) [14,42]

Immunomodulatory Effects:

Upregulation of antimicrobial peptides (cathelicidin, defensins) [43]
Modulation of innate and adaptive immunity (macrophage differentiation, T-cell regulation) [44]
Anti-inflammatory effects (downregulation of NF-κB, reduced cytokine storm) [45]

VITdAL-ICU Trial (2014): High-dose vitamin D₃ (540,000 IU loading, then 90,000 IU monthly) vs placebo in critically ill adults showed no difference in hospital length of stay (primary outcome) but reduced mortality in the subgroup with severe deficiency (<30 nmol/L, <12 ng/mL) [16]

VIOLET Trial (2019): Early high-dose vitamin D₃ (540,000 IU enterally) vs placebo in critically ill adults showed no mortality benefit and no reduction in hospital length of stay, leading to consensus against routine high-dose supplementation [46]

Vitamin C (Ascorbic Acid)

Vitamin C is a water-soluble antioxidant and cofactor for collagen synthesis, catecholamine synthesis, and immune function. [47]

Mechanism of Depletion in Critical Illness:

Massive oxidative stress during sepsis consumes vitamin C stores (plasma levels drop to <11 μmol/L within 24-48 hours) [19,20]
Enhanced renal clearance in polyuria
Redistribution into activated leukocytes and tissues
Inadequate intake and impaired intestinal absorption

Theoretical Benefits in Sepsis:

Antioxidant defense (scavenges reactive oxygen species)
Preservation of endothelial barrier integrity (reduces capillary leak) [48]
Catecholamine synthesis (cofactor for dopamine β-hydroxylase)
Immune function enhancement (neutrophil chemotaxis, phagocytosis) [49]

Evidence from Trials:

CITRIS-ALI Trial (2019, PMID 30625275): Vitamin C 50 mg/kg IV q6h vs placebo in sepsis-induced ARDS showed no improvement in organ dysfunction scores (primary outcome) but lower 28-day mortality (29.8% vs 46.3%, p=0.03 - secondary outcome) [50]
VITAMINS Trial (2020, PMID 31577396): Vitamin C 1.5 g IV q6h + thiamine 200 mg IV q12h + hydrocortisone 50 mg q6h vs hydrocortisone alone showed no difference in time alive and free of vasopressors (median 122 vs 125 hours, p=0.83) [51]
LOVIT Trial (2022, PMID 35939567): High-dose vitamin C (50 mg/kg q6h) vs placebo in septic shock showed higher mortality with vitamin C (44.5% vs 38.5%, p=0.09) and increased death/persistent organ dysfunction (50.1% vs 43.6%, p=0.03) [52]

Current Consensus: Routine high-dose vitamin C not recommended in sepsis; supplementation at RDA levels (100-200 mg/day) reasonable to prevent deficiency [53]

Selenium

Selenium is an essential trace element incorporated into selenoproteins with antioxidant (glutathione peroxidase), anti-inflammatory, and immunomodulatory functions. [54]

Mechanism of Deficiency in Critical Illness:

Redistribution into tissues (liver, muscle) during acute phase response
Enhanced oxidative consumption in sepsis
Renal and gastrointestinal losses (CRRT, diarrhea)
Inadequate intake

Selenoproteins and Function:

Glutathione peroxidase (GPx): Reduces hydrogen peroxide and lipid peroxides
Thioredoxin reductase: Maintains cellular redox state
Selenoprotein P: Selenium transport and antioxidant function
Deiodinases: Thyroid hormone activation [24,54]

Evidence for Supplementation:

Cochrane Review (2015, PMID 25927840): Selenium supplementation in critically ill patients (16 RCTs, n=2,084) showed no mortality benefit overall (RR 0.99, 95% CI 0.86-1.14), but subgroup analysis suggested potential benefit in sepsis [55]
Dosing: Supplementation trials used 500-1,000 mcg/day loading, then 500 mcg/day maintenance (significantly higher than RDA 55 mcg/day) [56]
Toxicity Risk: Chronic intake >400 mcg/day associated with selenosis (hair loss, garlic breath, neurological symptoms, nail changes) [57]

Australian Context: TGA-approved selenium supplements available (oral 150 mcg tablets, IV sodium selenite for TPN)

Zinc

Zinc is an essential trace element with roles in immune function, wound healing, protein synthesis, and enzyme catalysis (>300 zinc-dependent enzymes). [58]

Mechanism of Deficiency in Critical Illness:

Redistribution during acute phase response (hepatic sequestration, intracellular shift) [59]
Enhanced losses (diarrhea, fistulas, burns, CRRT)
Inadequate intake (malnutrition, parenteral nutrition without supplementation)
Impaired absorption (gastrointestinal disease)

Clinical Consequences:

Immune Dysfunction: Lymphopenia, reduced NK cell activity, impaired macrophage function, increased infection risk [60,61]
Delayed Wound Healing: Impaired collagen synthesis, epithelialization, cell migration [62]
Prolonged ICU Stay: Low zinc levels associated with higher APACHE II scores and mortality [63]

Evidence for Supplementation:

Routine supplementation in ICU: Limited evidence for routine use; supplementation (22-45 mg elemental zinc daily) reserved for documented deficiency or high-risk groups (burns, wounds, malnutrition) [64]
Toxicity: Chronic high-dose zinc (>40 mg/day) interferes with copper absorption, causing copper deficiency anemia and myeloneuropathy [65]

Vitamin B12 (Cobalamin) and Folate

Vitamin B12 and folate are essential for DNA synthesis, methylation reactions, and erythropoiesis. [66]

Deficiency in Critical Illness:

Malabsorption (pernicious anemia, ileal disease, gastric surgery)
Inadequate intake (malnutrition, strict vegan diet for B12)
Nitrous oxide exposure inactivates B12 (methionine synthase inhibition) [67]
Chronic disease (CKD, liver disease)

Clinical Consequences:

Megaloblastic Anemia: Macrocytic anemia with hypersegmented neutrophils [68]
Subacute Combined Degeneration of Cord (B12 deficiency): Demyelination of dorsal and lateral columns, causing sensory ataxia, weakness, paresthesias [69]
Hyperhomocysteinemia: Increased cardiovascular and thrombotic risk

Diagnosis and Treatment:

B12 deficiency: Serum B12 <150 pmol/L (<200 pg/mL); treatment: 1,000 mcg IM daily × 1 week, then weekly × 4 weeks, then monthly
Folate deficiency: Serum folate <7 nmol/L (<3 ng/mL), RBC folate <340 nmol/L; treatment: 5 mg oral daily [70]

Vitamin K

Vitamin K is a fat-soluble vitamin essential for activation of clotting factors (II, VII, IX, X) and anticoagulant proteins (protein C, protein S). [71]

Mechanism of Deficiency in Critical Illness:

Inadequate intake (NPO status, malnutrition)
Broad-spectrum antibiotics depleting vitamin K-producing gut flora [28]
Malabsorption (biliary obstruction, pancreatic insufficiency, short bowel syndrome)
Liver disease impairing vitamin K-dependent carboxylation

Clinical Consequences:

Coagulopathy: Prolonged PT/INR, bleeding risk [72]
Warfarin-Associated Coagulopathy: Vitamin K antagonism requiring reversal in bleeding/surgery

Management:

Non-bleeding vitamin K deficiency: Vitamin K 1-2.5 mg PO/IV daily [73]
Active bleeding or urgent surgery with elevated INR:
- "Warfarin reversal: 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg + vitamin K 5-10 mg IV slow infusion [74,75]"
- "Nutritional deficiency with bleeding: Vitamin K 5-10 mg IV + fresh frozen plasma if PT/INR >2.0 [76]"
Intracranial hemorrhage: 4-factor PCC + vitamin K 10 mg IV (faster INR normalization than FFP) [77,78]

Trace Elements (Copper, Manganese, Chromium, Molybdenum)

Copper:

Essential for ceruloplasmin, cytochrome c oxidase, superoxide dismutase
Deficiency: Anemia (sideroblastic), neutropenia, myeloneuropathy (mimics B12 deficiency) [79]
Causes: Prolonged TPN without supplementation, excessive zinc (antagonizes copper absorption), chronic diarrhea
Treatment: Copper sulfate 2-4 mg elemental copper daily [80]

Manganese:

Cofactor for superoxide dismutase, pyruvate carboxylase, arginase
Deficiency: Rare (nausea, dermatitis, hypocholesterolemia, skeletal abnormalities)
Toxicity more common: Prolonged TPN or occupational exposure causing parkinsonism [81]
RDA: 2.3 mg/day (men), 1.8 mg/day (women)

Chromium:

Potentiates insulin action, involved in glucose metabolism
Deficiency: Rare, reported with prolonged TPN (hyperglycemia, neuropathy, impaired nitrogen balance) [82]
RDA: 35 mcg/day (men), 25 mcg/day (women)

Molybdenum:

Cofactor for xanthine oxidase, aldehyde oxidase, sulfite oxidase
Deficiency: Extremely rare (tachycardia, headache, altered mental status) [83]
RDA: 45 mcg/day

Electrolytes as Micronutrients

While technically macrominerals, magnesium, phosphate, and calcium play critical roles in enzyme function and cellular processes, and deficiencies are common in ICU.

Magnesium:

Cofactor for >300 enzymes, regulates calcium channels, neuromuscular function
Hypomagnesemia (Mg <0.7 mmol/L or <1.7 mg/dL): Present in 20-65% of ICU patients [84]
Causes: Diuretics, CRRT, diarrhea, proton pump inhibitors, alcohol use
Consequences: Cardiac arrhythmias (torsades de pointes, atrial fibrillation), neuromuscular irritability, refractory hypokalemia and hypocalcemia [85]
Treatment: Magnesium sulfate 2-4 g (8-16 mmol) IV over 15-30 minutes for severe/symptomatic hypomagnesemia; 1-2 g q6-12h for asymptomatic [86]

Phosphate:

Essential for ATP synthesis, 2,3-DPG (oxygen delivery), phospholipid membranes
Hypophosphatemia (PO₄ <0.8 mmol/L or <2.5 mg/dL): Present in 30-80% of ICU patients [87,88]
Causes: Refeeding syndrome, CRRT, diuretics, respiratory alkalosis, diabetic ketoacidosis recovery
Consequences: Respiratory muscle weakness (prolonged ventilation), cardiac dysfunction, hemolysis, rhabdomyolysis, impaired oxygen delivery (leftward shift of oxygen-hemoglobin curve) [89,90]
REFEED Trial (2015, PMID 26653063): Caloric restriction to 20 kcal/hour for 48 hours in patients with hypophosphatemia after starting EN improved survival and reduced ventilator days [91]
Treatment: Phosphate 0.16-0.32 mmol/kg IV over 6-12 hours for moderate deficiency (0.32-0.65 mmol/L); 0.32-0.64 mmol/kg for severe (<0.32 mmol/L) [92]

Calcium:

Essential for muscle contraction, neurotransmission, coagulation, bone metabolism
Hypocalcemia (ionized Ca <1.0 mmol/L or <4.0 mg/dL): Present in 15-88% of ICU patients depending on definition [93]
Causes: Sepsis, acute kidney injury, massive transfusion (citrate toxicity), pancreatitis, vitamin D deficiency, hypoparathyroidism, hypomagnesemia
Consequences: Prolonged QT interval, arrhythmias, hypotension, tetany, seizures
Treatment: Calcium gluconate 1-2 g (2.3-4.6 mmol elemental Ca) IV over 10-20 minutes for symptomatic hypocalcemia; correct concurrent hypomagnesemia [94]

Clinical Presentation and Diagnosis

Thiamine Deficiency

Clinical Features:

Lactic Acidosis: Unexplained high anion gap metabolic acidosis with lactate >4 mmol/L despite adequate tissue perfusion and resuscitation [34,35]
Wernicke Encephalopathy: Acute confusion, ataxia, ophthalmoplegia (nystagmus, lateral rectus palsy, conjugate gaze palsy) - classic triad present in only 10-16% [36,95]
- Non-alcoholic WE: Hyperemesis gravidarum, malnutrition, post-bariatric surgery, prolonged parenteral nutrition [37]
Cardiovascular: High-output cardiac failure, tachycardia, edema ("wet beriberi") [38]
Peripheral Neuropathy: "Dry beriberi"

distal symmetric polyneuropathy, weakness, paresthesias

Diagnosis:

Erythrocyte transketolase activity (functional assay): Gold standard but rarely available acutely
Thiamine pyrophosphate (TPP) level (whole blood): <70 nmol/L suggests deficiency [96]
Plasma thiamine: <7 nmol/L deficient; not widely available
Clinical diagnosis: High index of suspicion; treat empirically before confirmatory testing in high-risk patients (malnutrition, chronic alcohol use, unexplained lactic acidosis)

EFNS Guidelines (2010, PMID 21143696): Recommend empiric treatment in all suspected cases; delay in treatment can lead to irreversible Korsakoff psychosis [95]

Vitamin D Deficiency

Clinical Features:

Often subclinical in acute setting
Chronic deficiency: Muscle weakness, bone pain, osteomalacia, increased falls risk
Associated with higher ICU mortality, longer length of stay, increased infection risk [17,18]

Diagnosis:

25-Hydroxyvitamin D [25(OH)D]: Standard marker
- "Deficiency: <50 nmol/L (<20 ng/mL)"
- "Severe deficiency: <30 nmol/L (<12 ng/mL)"
- "Insufficiency: 50-75 nmol/L (20-30 ng/mL)"
- "Sufficiency: >75 nmol/L (>30 ng/mL) [41]"
1,25-Dihydroxyvitamin D: Not useful for screening (normal or elevated in deficiency due to secondary hyperparathyroidism)

Australian/NZ Context: Medicare-funded 25(OH)D testing available for high-risk groups (osteoporosis, malabsorption, CKD, Aboriginal and Torres Strait Islander peoples)

Vitamin C Deficiency

Clinical Features:

Acute depletion in sepsis often asymptomatic
Chronic deficiency (scurvy): Petechiae, ecchymoses, gingival bleeding, poor wound healing, perifollicular hemorrhage [97]

Diagnosis:

Plasma ascorbic acid: <11 μmol/L (<0.2 mg/dL) deficient; 11-23 μmol/L hypovitaminosis C [21]
Limited availability of testing in acute setting

Selenium Deficiency

Clinical Features:

Acute deficiency: Often asymptomatic in ICU; associated with prolonged ventilation, increased infection risk
Chronic deficiency: Cardiomyopathy (Keshan disease), myopathy, immune dysfunction [98]

Diagnosis:

Plasma selenium: <70 μg/L deficient [22]
Selenoprotein P: More sensitive marker of functional selenium status [24]

Zinc Deficiency

Clinical Features:

Acute redistribution in critical illness (low plasma zinc with normal/high tissue stores)
Chronic deficiency: Dermatitis (acrodermatitis enteropathica), alopecia, impaired wound healing, immune dysfunction, taste abnormalities [99]

Diagnosis:

Plasma zinc: <10.7 μmol/L (<70 μg/dL) deficient
Interpretation difficult in acute phase response (inflammation lowers plasma zinc independent of total body stores) [26]

Vitamin B12 and Folate Deficiency

Clinical Features:

Megaloblastic anemia: Fatigue, pallor, glossitis, angular stomatitis
B12-specific: Subacute combined degeneration (paresthesias, sensory ataxia, weakness, decreased vibration/proprioception) [69]

Diagnosis:

Serum B12: <150 pmol/L (<200 pg/mL) deficient
Serum folate: <7 nmol/L (<3 ng/mL) deficient
RBC folate: More accurate for folate status (>340 nmol/L normal)
Methylmalonic acid (MMA): Elevated in B12 deficiency (>0.4 μmol/L)
Homocysteine: Elevated in both B12 and folate deficiency [100]

Vitamin K Deficiency

Clinical Features:

Coagulopathy: Bruising, bleeding (GI, mucosal, surgical sites)
Prolonged PT/INR (factor VII has shortest half-life, affected first) [72]

Diagnosis:

PT/INR: Prolonged (INR >1.5-2.0)
Activated Partial Thromboplastin Time (aPTT): Prolonged in severe deficiency
PIVKA-II (Protein Induced by Vitamin K Absence): Specific marker, not widely available

Management and Supplementation Protocols

Thiamine Supplementation

Prophylactic Supplementation (High-Risk Patients):

Malnutrition, chronic alcohol use, refeeding syndrome risk: Thiamine 200-300 mg IV daily × 3-5 days, then 100 mg oral daily [101]
Before dextrose administration: Thiamine should ALWAYS be given before or concurrently with dextrose-containing fluids in at-risk patients to prevent precipitating Wernicke encephalopathy [39,40]

Therapeutic Dosing:

Wernicke Encephalopathy (suspected or confirmed):
- Thiamine 500 mg IV TID × 3-5 days, then 250 mg IV/IM daily × 3-5 days, then 100 mg oral daily [95]
- EFNS guidelines: High-dose IV thiamine (200-500 mg TID) should be started immediately in suspected cases [95]
Lactic Acidosis (suspected thiamine deficiency):
- Thiamine 200 mg IV q8-12h; response typically seen within 12-24 hours (lactate decrease) [34,35]
Septic Shock:
- VITAMINS Trial protocol: Thiamine 200 mg IV q12h × 4 days [51]
- No proven mortality benefit in RCTs; reasonable to supplement at 100-200 mg/day to prevent deficiency [13]

Australian TGA-Approved Formulations:

Thiamine hydrochloride 100 mg tablets (oral)
Thiamine 100 mg/mL injection (IM/slow IV) - PBS listed

Vitamin D Supplementation

Routine Supplementation (Non-Critical Illness):

Deficiency (<50 nmol/L): Cholecalciferol 3,000-5,000 IU oral daily × 6-8 weeks, then 1,000-2,000 IU daily maintenance [102]
Severe deficiency (<30 nmol/L): Loading dose 300,000 IU (e.g., 50,000 IU weekly × 6 weeks), then maintenance

Critical Illness:

VITdAL-ICU and VIOLET Trials: High-dose vitamin D (540,000 IU) showed no mortality benefit in unselected ICU patients [16,46]
Current Recommendation: Routine high-dose supplementation NOT recommended; standard replacement (1,000-2,000 IU daily) reasonable for documented deficiency [53]

Australian TGA-Approved Formulations:

Cholecalciferol (Vitamin D₃) 1,000 IU, 2,000 IU, 5,000 IU capsules - PBS listed for osteoporosis
Colecalciferol 50,000 IU capsules (PBS for severe deficiency)

Vitamin C Supplementation

Routine Supplementation (Preventing Deficiency):

Enteral/parenteral nutrition: 100-200 mg/day (RDA: 90 mg/day men, 75 mg/day women) [103]

High-Dose Vitamin C in Sepsis:

CITRIS-ALI protocol: Vitamin C 50 mg/kg IV q6h × 4 days [50]
VITAMINS protocol: Vitamin C 1.5 g IV q6h × 4 days [51]
LOVIT Trial: High-dose vitamin C associated with increased mortality/organ dysfunction; NOT recommended [52]

Current Consensus (Surviving Sepsis Campaign 2021): Routine high-dose vitamin C (>3 g/day) NOT recommended in sepsis; standard supplementation (100-200 mg/day) reasonable [53]

Australian TGA-Approved Formulations:

Ascorbic acid 500 mg, 1,000 mg tablets (oral) - OTC
Ascorbic acid 500 mg/5 mL injection (IV) - hospital use

Selenium Supplementation

Prophylactic Supplementation:

Parenteral nutrition: 60-100 mcg/day (sodium selenite) [104]
Enteral nutrition: 55 mcg/day (RDA)

Therapeutic Supplementation (Sepsis/Critical Illness):

Loading dose: 500-1,000 mcg IV on day 1
Maintenance: 500 mcg IV daily × 10-14 days [56]
Caution: Selenium supplementation NOT routinely recommended (no mortality benefit in Cochrane review); consider in documented deficiency or severe sepsis [55]

Toxicity Risk:

Chronic intake >400 mcg/day associated with selenosis
Symptoms: Garlic breath odour, hair/nail loss, nausea, neurological symptoms [57]

Australian TGA-Approved Formulations:

Selenium 150 mcg tablets (oral) - OTC
Sodium selenite 100 mcg/mL injection (IV) - for TPN

Zinc Supplementation

Prophylactic Supplementation:

Parenteral nutrition: 2.5-5 mg elemental zinc daily (higher in high GI losses: 12-17 mg/day) [105]
Enteral nutrition: 11 mg/day men, 8 mg/day women (RDA)

Therapeutic Supplementation:

Documented deficiency, wound healing, burns: Zinc sulfate 220 mg PO TID (50 mg elemental zinc TID) or 22-45 mg elemental zinc IV daily [64]
Duration: 2-4 weeks, reassess

Toxicity Risk:

Chronic high-dose zinc (>40 mg/day) interferes with copper absorption
Monitor copper levels with prolonged supplementation [65]

Australian TGA-Approved Formulations:

Zinc sulfate 220 mg tablets (50 mg elemental zinc) - OTC
Zinc 5 mg/mL injection (IV) - for TPN

Vitamin B12 and Folate Supplementation

Vitamin B12:

Deficiency: Cyanocobalamin or hydroxocobalamin 1,000 mcg IM daily × 1 week, then weekly × 4 weeks, then monthly lifelong [70]
Pernicious anemia: Lifelong monthly IM B12
Oral high-dose: Cyanocobalamin 1,000-2,000 mcg oral daily (alternative for non-severe deficiency)

Folate:

Deficiency: Folic acid 5 mg oral daily × 1-4 months [70]
Prophylaxis in pregnancy: Folic acid 400-800 mcg daily (reduces neural tube defects)

Australian PBS:

Cyanocobalamin 1,000 mcg injection (PBS)
Folic acid 5 mg tablets (PBS)

Vitamin K Supplementation

Prophylaxis (High-Risk Patients):

Prolonged antibiotics, malnutrition, TPN: Vitamin K 5-10 mg oral/IV weekly [28]

Treatment:

Non-bleeding, elevated INR (nutritional deficiency):
- Vitamin K 1-2.5 mg PO/IV daily × 3 days [73]
Active bleeding or pre-operative (warfarin reversal):
- Minor bleeding: Vitamin K 5-10 mg slow IV + withhold warfarin [74]
- Major bleeding: 4-factor PCC 25-50 U/kg IV + vitamin K 10 mg slow IV [75,76]
- Intracranial hemorrhage: 4-factor PCC + vitamin K 10 mg IV immediately [77,78]

Australian TGA-Approved Formulations:

Phytomenadione (Vitamin K1) 10 mg tablets - PBS
Phytomenadione 10 mg/mL injection (slow IV, max 1 mg/min to reduce anaphylactoid risk) - PBS
4-factor PCC (Prothrombinex-VF 500 IU) - PBS for warfarin reversal

Trace Elements (Copper, Manganese, Chromium, Molybdenum)

Parenteral Nutrition:

Standard trace element solutions provide:
- "Copper: 0.3-0.5 mg/day"
- "Manganese: 60-100 mcg/day (omit in cholestasis due to biliary excretion)"
- "Chromium: 10-15 mcg/day"
- "Molybdenum: 20-40 mcg/day [106]"

Copper Deficiency Treatment:

Copper sulfate 2-4 mg elemental copper daily PO/IV × 6-12 weeks [80]

Electrolytes (Magnesium, Phosphate, Calcium)

Magnesium:

Prophylaxis (diuretics, CRRT): Magnesium oxide 400 mg oral daily
Treatment:
- "Severe/symptomatic (<0.5 mmol/L): Magnesium sulfate 2-4 g (8-16 mmol) IV over 15-30 minutes [86]"
- "Moderate (0.5-0.7 mmol/L): Magnesium sulfate 1-2 g IV q6-12h"
- "Arrhythmias (torsades): Magnesium sulfate 2 g IV bolus, repeat PRN"

Phosphate:

Prophylaxis (refeeding syndrome risk): Monitor PO₄ daily; start EN at 20 kcal/hour, increase slowly [91]
Treatment:
- "Severe (<0.32 mmol/L): Sodium/potassium phosphate 0.32-0.64 mmol/kg IV over 6-12 hours [92]"
- "Moderate (0.32-0.65 mmol/L): Sodium/potassium phosphate 0.16-0.32 mmol/kg IV"
- "Mild (0.65-0.8 mmol/L): Oral phosphate 1-2 g TID"

Calcium:

Symptomatic hypocalcemia (ionized Ca <1.0 mmol/L with tetany, seizures, hypotension):
- Calcium gluconate 10% 1-2 g (10-20 mL) IV over 10-20 minutes [94]
- "Maintenance: Calcium gluconate 1 g IV q6h or calcium infusion 0.5-1.5 mg/kg/hour elemental Ca"
- Correct concurrent hypomagnesemia (magnesium deficiency prevents calcium correction)

Monitoring Strategies

Routine ICU Micronutrient Monitoring

At ICU Admission (High-Risk Patients):

Thiamine (erythrocyte transketolase or plasma thiamine if available) in malnutrition, chronic alcohol use, unexplained lactic acidosis
Vitamin D (25(OH)D) in prolonged ICU stay expected, immunocompromised, chronic disease
Vitamin B12 and folate in malnutrition, macrocytic anemia, neurological symptoms
Zinc, selenium in severe sepsis, burns, prolonged critical illness (if available)

During ICU Stay:

Refeeding syndrome risk (BMI <16, minimal intake >10 days, chronic malnutrition):
- "Phosphate, magnesium, potassium, thiamine: Daily × 5-7 days after starting EN/PN [39,40,91]"
Electrolytes (magnesium, phosphate, calcium, potassium): Daily in all ICU patients, more frequent in CRRT, refeeding, massive transfusion
INR/PT: Daily in patients on warfarin, broad-spectrum antibiotics, liver disease (monitor for vitamin K deficiency)

Parenteral Nutrition:

Trace elements (copper, selenium, zinc, manganese) at baseline and q2-4 weeks if prolonged TPN [104,106]
Vitamin B12, folate, vitamin D q4-6 weeks in prolonged TPN

Laboratory Parameters and Targets

Micronutrient	Test	Target Range	Frequency
Thiamine	Plasma thiamine	>7 nmol/L	Admission if high risk
Vitamin D	25(OH)D	>50 nmol/L (>20 ng/mL)	Admission, q4-6 weeks if prolonged ICU
Vitamin C	Plasma ascorbic acid	>23 μmol/L	Not routine (limited availability)
Selenium	Plasma selenium	>70 μg/L	Baseline if severe sepsis/burns
Zinc	Plasma zinc	10.7-18.4 μmol/L (70-120 μg/dL)	Baseline if malnutrition/burns
Vitamin B12	Serum B12	>150 pmol/L (>200 pg/mL)	If anemia, neuropathy
Folate	Serum folate	>7 nmol/L (>3 ng/mL)	If anemia, macrocytosis
Magnesium	Serum magnesium	0.7-1.1 mmol/L (1.7-2.6 mg/dL)	Daily in ICU
Phosphate	Serum phosphate	0.8-1.5 mmol/L (2.5-4.6 mg/dL)	Daily in ICU, q6-12h if refeeding
Calcium	Ionized calcium	1.1-1.3 mmol/L (4.4-5.2 mg/dL)	Daily in ICU
Copper	Serum copper	11-22 μmol/L (70-140 μg/dL)	q4 weeks if prolonged TPN

Complications and Toxicity

Hypervitaminosis and Toxicity

Vitamin D Toxicity:

Chronic intake >10,000 IU/day → hypercalcemia, nephrocalcinosis, renal failure [107]
Symptoms: Nausea, vomiting, polyuria, polydipsia, confusion, renal stones
Treatment: Stop vitamin D, IV fluids, calcitonin or bisphosphonates for severe hypercalcemia

Selenium Toxicity (Selenosis):

Chronic intake >400 mcg/day or acute overdose >1,000 mcg/day [57]
Symptoms: Garlic breath odour, metallic taste, hair/nail loss, nausea, diarrhea, fatigue, neurological symptoms (peripheral neuropathy)
Treatment: Stop supplementation, supportive care

Vitamin A Toxicity (Hypervitaminosis A):

Chronic intake >10,000 IU/day → hepatotoxicity, intracranial hypertension (pseudotumor cerebri), bone pain [108]
Acute overdose: Nausea, vomiting, blurred vision, ataxia
Treatment: Stop vitamin A, monitor liver function, supportive care

Zinc Toxicity:

Acute: Nausea, vomiting, abdominal pain, diarrhea (typically >200 mg single dose) [65]
Chronic high-dose (>40 mg/day): Copper deficiency (microcytic anemia, neutropenia, myeloneuropathy)
Treatment: Stop zinc, copper supplementation if deficient

Vitamin K Toxicity:

Rare with vitamin K1 (phytomenadione)
Vitamin K3 (menadione, not used clinically): Hemolytic anemia, hyperbilirubinemia, kernicterus in neonates [71]

Iron Overload (Hemochromatosis):

Chronic supplementation without deficiency → hepatotoxicity, cardiomyopathy, diabetes, arthropathy
Monitor ferritin, transferrin saturation; avoid routine iron supplementation without documented deficiency [109]

Refeeding Syndrome

Definition: Metabolic disturbances following reintroduction of nutrition after prolonged fasting or malnutrition, characterized by hypophosphatemia, hypomagnesemia, hypokalemia, thiamine deficiency, and fluid overload. [39,40]

Pathophysiology:

Insulin surge with carbohydrate intake drives intracellular shift of phosphate, magnesium, potassium
Thiamine rapidly consumed to metabolize glucose → Wernicke encephalopathy risk
Fluid retention due to insulin-mediated sodium reabsorption

Risk Factors:

BMI <16 kg/m² OR unintentional weight loss >15% in 3-6 months
Minimal intake >10 days
History of chronic alcohol use, anorexia nervosa, malabsorption
Electrolyte abnormalities before feeding (K <3.5, PO₄ <0.65, Mg <0.5 mmol/L)

Clinical Consequences:

Cardiac: Arrhythmias, heart failure, sudden death
Respiratory: Respiratory muscle weakness, prolonged ventilation
Neurological: Wernicke encephalopathy, seizures, altered mental status, paresthesias
Hematological: Hemolysis (severe hypophosphatemia), rhabdomyolysis

Prevention (ASPEN/ESPEN Guidelines): [39,91,110]

Identify high-risk patients
Thiamine supplementation: 200-300 mg IV daily BEFORE starting nutrition
Correct electrolytes BEFORE feeding:
- Phosphate >0.65 mmol/L (>2.0 mg/dL)
- Magnesium >0.5 mmol/L (>1.2 mg/dL)
- Potassium >3.5 mmol/L
Start low, go slow:
- Energy: 10-20 kcal/kg/day initially (≤50% estimated requirements)
- Protein: 1.2-1.5 g/kg/day (protein does not trigger refeeding)
- Increase by 20% every 2-3 days to target by days 5-7
Monitor daily × 5-7 days: Phosphate, magnesium, potassium, glucose, fluid balance

REFEED Trial Protocol: If hypophosphatemia develops (PO₄ <0.65 mmol/L), restrict calories to 20 kcal/hour × 48 hours while correcting electrolytes [91]

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples

Micronutrient Deficiency Prevalence:

Vitamin D deficiency: 30-60% prevalence despite high sun exposure (skin pigmentation, clothing, indoor occupations) [9,31]
Iron deficiency: Higher prevalence due to chronic disease, dietary factors, hookworm in remote areas [111]
Zinc deficiency: Common in chronic kidney disease, diabetes (higher prevalence in Aboriginal populations)
Folate deficiency: Lower intake of folate-rich foods in remote areas

Chronic Disease Burden:

Diabetes mellitus: 3-4× higher prevalence → vitamin D, B12, zinc deficiencies
Chronic kidney disease: 2-3× higher prevalence → vitamin D, iron, erythropoietin deficiencies [112]
Cardiovascular disease: Higher prevalence → folate, B12 deficiencies (hyperhomocysteinemia)

Food Insecurity and Access:

Remote communities: Limited access to fresh fruit/vegetables (vitamin C, folate)
"Food deserts": High cost of nutritious food, reliance on processed/canned foods
Traditional bush foods: Rich in micronutrients but reduced consumption [113]

Cultural Considerations:

Involve Aboriginal Health Workers (AHW) in nutrition counseling and supplement education
Respect for Elders and family-centered decision-making
Culturally appropriate communication (yarning, visual aids)
Consider barriers to supplement adherence (literacy, cost, medication complexity)

Supplementation in Remote ICU Settings:

Royal Flying Doctor Service (RFDS) retrievals: Thiamine 200-300 mg IV before dextrose in suspected malnutrition
Telehealth support for remote ICU/high dependency units: Micronutrient monitoring protocols

Māori Health (New Zealand)

Micronutrient Deficiency Prevalence:

Vitamin D deficiency: 30-50% prevalence (higher latitude, skin pigmentation) [114]
Iron deficiency: Higher rates in Māori women and children
Folate deficiency: Lower intake in socioeconomically disadvantaged groups

Chronic Disease Burden:

Diabetes: 1.5-2× higher prevalence → vitamin D, B12 deficiencies
Cardiovascular disease: Higher prevalence → folate, B12 deficiencies
Chronic kidney disease: Higher prevalence → vitamin D, iron deficiencies

Cultural Considerations:

Whānau (family)-centered care: Involve extended family in nutrition decisions
Tikanga (cultural practices): Respect for cultural protocols, kaumātua (elders) involvement
Māori health providers: Utilize kaupapa Māori services for culturally safe supplementation counseling
Te Tiriti o Waitangi obligations: Equitable access to micronutrient testing and supplementation

New Zealand Formulary:

PHARMAC-funded micronutrient supplements (thiamine, vitamin D, B12, folate, iron)
Community pharmacy access for supplementation in remote areas

Australian and New Zealand Context

TGA-Approved Micronutrient Supplements

Prescription Medications (PBS-Listed):

Thiamine hydrochloride 100 mg tablets, 100 mg/mL injection
Cyanocobalamin 1,000 mcg injection
Folic acid 5 mg tablets
Phytomenadione (Vitamin K1) 10 mg tablets, 10 mg/mL injection
Cholecalciferol 1,000-50,000 IU capsules (PBS for osteoporosis, severe deficiency)

Over-the-Counter (OTC):

Multivitamin preparations (variable micronutrient content)
Vitamin C 500-1,000 mg tablets
Zinc sulfate 220 mg tablets
Selenium 150 mcg tablets
Magnesium oxide 400-500 mg tablets

Parenteral Nutrition Additives:

Trace element solutions (copper, selenium, zinc, manganese, chromium, molybdenum)
Water-soluble vitamin solutions (B-complex, vitamin C)
Fat-soluble vitamin solutions (A, D, E, K)

PBS Coverage and Restrictions

Vitamin D:

PBS coverage for osteoporosis (with DEXA evidence), malabsorption, CKD, post-bariatric surgery
Unrestricted PBS for Aboriginal and Torres Strait Islander peoples ≥50 years

Vitamin B12:

PBS coverage for pernicious anemia, documented B12 deficiency, post-gastrectomy, ileal resection

Folic Acid:

PBS coverage for documented deficiency, pregnancy, chronic hemolytic anemia, methotrexate therapy

Thiamine:

PBS coverage for Wernicke encephalopathy, beriberi, documented deficiency, chronic alcohol use

Vitamin K:

PBS coverage for warfarin reversal, vitamin K deficiency bleeding, malabsorption

ANZICS Guidelines and Recommendations

ANZICS Clinical Trials Group Nutrition Recommendations (2020): [24]

Thiamine 100-300 mg IV daily for patients at risk of Wernicke encephalopathy or refeeding syndrome
Routine high-dose vitamin C or selenium supplementation NOT recommended (insufficient evidence)
Monitor electrolytes (magnesium, phosphate, potassium) daily in all ICU patients
Trace element supplementation as per TPN formulations for patients on parenteral nutrition >7 days

ANZICS CORE (Critical Care Resources Registry):

National database tracking ICU resources, including availability of micronutrient testing and supplementation in Australian/NZ ICUs

Evidence Summary and Key Trials

Thiamine Trials

Donnino et al. (2016, PMID 26733151): Thiamine as a metabolic resuscitator in septic shock - RCT of thiamine 200 mg IV q12h vs placebo; no mortality benefit overall, but improved lactate clearance in thiamine-deficient patients [11]
VITAMINS Trial (2020, PMID 31577396): Vitamin C + thiamine + hydrocortisone vs hydrocortisone alone in septic shock - no difference in time alive and free of vasopressors [51]

Vitamin D Trials

VITdAL-ICU Trial (2014, PMID 25268295): High-dose vitamin D₃ (540,000 IU loading) vs placebo in critically ill - no difference in hospital length of stay; reduced mortality in severe deficiency subgroup (<30 nmol/L) [16]
VIOLET Trial (2019, PMID 30761995): Early high-dose vitamin D₃ vs placebo in critically ill - no mortality benefit [46]

Vitamin C Trials

CITRIS-ALI Trial (2019, PMID 30625275): Vitamin C 50 mg/kg q6h vs placebo in sepsis-induced ARDS - no improvement in organ dysfunction scores (primary outcome), but lower 28-day mortality (secondary outcome, p=0.03) [50]
VITAMINS Trial (2020, PMID 31577396): Vitamin C 1.5 g q6h + thiamine + hydrocortisone vs hydrocortisone alone - no benefit [51]
LOVIT Trial (2022, PMID 35939567): High-dose vitamin C vs placebo in septic shock - higher mortality and organ dysfunction with vitamin C; NOT recommended [52]

Selenium Trials

Cochrane Review (2015, PMID 25927840): Selenium supplementation in critically ill (16 RCTs, n=2,084) - no mortality benefit overall (RR 0.99, 95% CI 0.86-1.14) [55]

Phosphate and Refeeding Syndrome Trials

REFEED Trial (2015, PMID 26653063): Caloric restriction to 20 kcal/hour × 48 hours in hypophosphatemia after starting EN - improved survival and reduced ventilator days [91]
da Silva et al. ASPEN Consensus (2020, PMID 32115710): Standardized definition of refeeding syndrome and prevention strategies [39]

Vitamin K and Warfarin Reversal Trials

Sarode et al. (2013, PMID 23559606): 4-factor PCC vs FFP for warfarin-induced major bleeding - PCC superior for rapid INR normalization and hemostasis [75]
INCH Trial (2016, PMID 26343511): PCC vs FFP in warfarin-associated intracranial hemorrhage - PCC faster INR normalization [78]

Assessment Content

SAQ Practice Question 1: Thiamine Deficiency and Lactic Acidosis (15 marks)

Question: A 58-year-old man with chronic alcohol use disorder is admitted to ICU with septic shock secondary to aspiration pneumonia. He is intubated, mechanically ventilated, and requiring norepinephrine 0.3 mcg/kg/min. Initial lactate is 8.2 mmol/L. After 4 hours of resuscitation with 4 L crystalloid and antibiotics, lactate remains 7.8 mmol/L despite MAP 72 mmHg, ScvO₂ 74%, and CVP 12 mmHg.

(a) List THREE micronutrient deficiencies that should be considered in this patient and explain their relevance to his presentation. (6 marks)

(b) Explain the pathophysiology of thiamine deficiency causing lactic acidosis. (4 marks)

(c) Outline your immediate management of suspected thiamine deficiency in this patient, including dosing and route. (3 marks)

(d) What other clinical features would suggest Wernicke encephalopathy, and why is early treatment critical? (2 marks)

Model Answer:

(a) THREE micronutrient deficiencies (6 marks - 2 marks each):

Thiamine (Vitamin B1) deficiency:
- Chronic alcohol use is the most common cause of thiamine deficiency in developed countries (malnutrition, reduced intake, impaired absorption, increased metabolic demand)
- Thiamine deficiency causes lactic acidosis due to pyruvate dehydrogenase dysfunction, preventing pyruvate entry into the Krebs cycle and shunting to lactate production ("Type B" lactic acidosis)
- This patient has persistent lactic acidosis despite adequate resuscitation (MAP, ScvO₂ normal), suggesting metabolic cause
Magnesium deficiency:
- Chronic alcohol use causes urinary magnesium wasting and poor intake
- Hypomagnesemia predisposes to arrhythmias, particularly in septic shock with catecholamine use
- Refractory hypokalemia and hypocalcemia occur with magnesium deficiency
Folate and/or Vitamin B12 deficiency:
- Chronic alcohol use associated with poor nutrition and reduced folate intake
- Chronic gastritis from alcohol impairs intrinsic factor production (B12 malabsorption)
- Megaloblastic anemia may contribute to reduced oxygen-carrying capacity

(b) Pathophysiology of thiamine deficiency causing lactic acidosis (4 marks):

Thiamine (as thiamine pyrophosphate, TPP) is an essential cofactor for the pyruvate dehydrogenase (PDH) complex, which catalyzes the conversion of pyruvate to acetyl-CoA for entry into the Krebs cycle. (1 mark)

In thiamine deficiency, the PDH complex cannot function, preventing pyruvate from entering aerobic metabolism. Instead, pyruvate is shunted to anaerobic metabolism via lactate dehydrogenase, converting pyruvate to lactate. (1 mark)

This results in "Type B" lactic acidosis - elevated lactate in the presence of adequate tissue oxygenation and perfusion (normal ScvO₂, MAP, CVP). The lactic acidosis persists despite fluid resuscitation because the underlying metabolic defect is not corrected. (1 mark)

Thiamine is also a cofactor for α-ketoglutarate dehydrogenase (Krebs cycle) and transketolase (pentose phosphate pathway), further impairing cellular energy production and causing accumulation of metabolic byproducts. (1 mark)

(c) Immediate management of suspected thiamine deficiency (3 marks):

Thiamine 200-300 mg IV immediately BEFORE any dextrose-containing fluids (to prevent precipitating Wernicke encephalopathy) (1 mark)
Dosing regimen:
- Thiamine 200-500 mg IV TID × 3-5 days (high-dose for suspected Wernicke encephalopathy)
- Then 100 mg IV/IM daily, transition to 100 mg oral daily when tolerating enteral nutrition (1 mark)
Monitoring:
- Repeat lactate q2-4h; expect decrease within 12-24 hours if thiamine-deficient
- Monitor for clinical improvement (mental status, ataxia, ophthalmoplegia if present)
- Correct concurrent electrolyte abnormalities (magnesium, phosphate, potassium) (1 mark)

(d) Clinical features of Wernicke encephalopathy and importance of early treatment (2 marks):

Clinical Features (1 mark):

Classic triad (only 10-16% of cases): acute confusion/encephalopathy, ataxia, ophthalmoplegia (nystagmus, lateral rectus palsy, conjugate gaze palsy)
Non-specific features more common: altered mental status, hypothermia, hypotension, delirium

Importance of Early Treatment (1 mark):

Untreated or delayed treatment can lead to irreversible Korsakoff psychosis (chronic amnesia, confabulation, apathy) in 80% of Wernicke cases
Mortality 10-20% if untreated; permanent neurological damage in survivors
Thiamine is safe (even in excess) and should be given empirically in any at-risk patient

SAQ Practice Question 2: Refeeding Syndrome and Micronutrient Monitoring (15 marks)

Question: A 62-year-old woman with advanced ovarian cancer is admitted to ICU with septic shock secondary to bowel perforation. She has had minimal oral intake for 3 weeks due to nausea and vomiting. BMI is 17 kg/m². She undergoes emergency laparotomy with Hartmann's procedure and is transferred to ICU intubated. On day 2, you plan to start enteral nutrition via nasojejunal tube.

(a) Identify THREE risk factors for refeeding syndrome in this patient. (3 marks)

(b) Explain the pathophysiology of refeeding syndrome, including the role of thiamine deficiency. (5 marks)

(c) Outline your prevention and monitoring strategy for refeeding syndrome in this patient, including:

Pre-feeding interventions (2 marks)
Nutrition initiation protocol (2 marks)
Monitoring plan (3 marks)

Model Answer:

(a) THREE risk factors for refeeding syndrome (3 marks - 1 mark each):

BMI <18.5 kg/m² (17 kg/m² in this patient): Severe malnutrition depletes intracellular electrolyte and vitamin stores, increasing risk of refeeding syndrome
Minimal oral intake for >10 days (3 weeks in this patient): Prolonged fasting or very low caloric intake (<400 kcal/day) is a major risk factor for refeeding syndrome due to adaptive metabolic changes
Critical illness and major surgery: Septic shock and emergency bowel surgery increase metabolic stress and micronutrient consumption, exacerbating deficiencies and refeeding risk

Other acceptable answers: Advanced cancer (cachexia, anorexia, malnutrition), nausea/vomiting (reduced intake, possible electrolyte losses)

(b) Pathophysiology of refeeding syndrome and role of thiamine deficiency (5 marks):

Metabolic Adaptation During Starvation (1 mark): During prolonged fasting, the body adapts to using fat and protein for energy (ketosis), with reduced insulin secretion and low-normal serum electrolytes. Intracellular electrolytes (phosphate, potassium, magnesium) become depleted as they are consumed for basal metabolism, but serum levels may remain normal due to reduced cellular uptake.

Refeeding-Induced Metabolic Shifts (2 marks): When carbohydrate-containing nutrition is reintroduced, insulin secretion surges. Insulin drives glucose, phosphate, potassium, and magnesium into cells for anabolic metabolism (glycogen synthesis, protein synthesis, ATP production). This causes:

Hypophosphatemia: Phosphate consumed for ATP synthesis, 2,3-DPG production, and glycolysis
Hypokalemia: Potassium shifts intracellular for protein synthesis and glycogen deposition
Hypomagnesemia: Magnesium depleted as cofactor for ATP-dependent processes

Additionally, insulin causes renal sodium and water retention, leading to volume overload and edema.

Thiamine Deficiency in Refeeding Syndrome (2 marks): Thiamine (vitamin B1) is rapidly consumed when carbohydrate metabolism is reactivated. Thiamine is an essential cofactor for:

Pyruvate dehydrogenase (PDH): Converts pyruvate to acetyl-CoA for the Krebs cycle
α-Ketoglutarate dehydrogenase: Krebs cycle enzyme
Transketolase: Pentose phosphate pathway

Reintroducing carbohydrates without thiamine supplementation can precipitate:

Lactic acidosis: PDH dysfunction shunts pyruvate to lactate
Wernicke encephalopathy: Acute thiamine depletion in brain (confusion, ataxia, ophthalmoplegia)
Cardiovascular failure: High-output failure ("wet beriberi"), arrhythmias, sudden death

(c) Prevention and monitoring strategy for refeeding syndrome (7 marks):

Pre-Feeding Interventions (2 marks):

Thiamine supplementation: Thiamine 200-300 mg IV daily × 3-5 days BEFORE starting nutrition (prevents Wernicke encephalopathy and lactic acidosis)
Correct electrolyte abnormalities BEFORE feeding:
- Target phosphate >0.65 mmol/L (>2.0 mg/dL)
- Target magnesium >0.5 mmol/L (>1.2 mg/dL)
- Target potassium >3.5 mmol/L
- Administer supplemental phosphate, magnesium, potassium IV if deficient

Nutrition Initiation Protocol (2 marks):

"Start low, go slow" approach:
- Calculate estimated energy requirements: 25-30 kcal/kg/day for target weight
- Start at 10-20 kcal/kg/day (≤50% of target) on day 1 (approximately 300-400 kcal/day for this patient)
- Increase by 20% every 2-3 days to reach target by days 5-7
Protein intake: Start at 1.2-1.5 g/kg/day (protein does NOT trigger refeeding syndrome and should NOT be restricted)

Monitoring Plan (3 marks):

Electrolyte monitoring (daily × 5-7 days after starting nutrition):
- Phosphate, magnesium, potassium, sodium, glucose
- If hypophosphatemia develops (PO₄ <0.65 mmol/L), REDUCE caloric intake to 20 kcal/hour × 48 hours while correcting electrolytes (REFEED Trial protocol)
Clinical monitoring:
- Fluid balance (input/output, daily weights) - watch for fluid overload (peripheral edema, pulmonary edema)
- Cardiovascular (heart rate, rhythm, blood pressure) - watch for arrhythmias, heart failure
- Neurological (mental status, ataxia, eye movements) - watch for Wernicke encephalopathy
Supplementation:
- Continue thiamine 100-300 mg IV daily
- Supplement phosphate, magnesium, potassium as needed to maintain normal levels
- Consider multivitamin and trace element supplementation

Viva Scenario 1: Comprehensive Micronutrient Management in Critical Illness (20 marks)

Scenario: You are the ICU registrar on call. A 55-year-old woman is admitted to ICU with severe septic shock secondary to necrotizing pancreatitis. She has a 10-year history of alcohol use disorder and has had minimal oral intake for 2 weeks due to abdominal pain and vomiting. On admission, she is intubated, mechanically ventilated, and requiring norepinephrine 0.4 mcg/kg/min.

Initial Investigations:

Lactate 9.5 mmol/L
pH 7.22, PaCO₂ 35 mmHg, HCO₃⁻ 14 mmol/L, BE -12
Na⁺ 132 mmol/L, K⁺ 3.2 mmol/L, Cl⁻ 98 mmol/L
Mg²⁺ 0.4 mmol/L, PO₄³⁻ 0.5 mmol/L, ionized Ca²⁺ 0.9 mmol/L
Glucose 18.2 mmol/L
Hb 98 g/L (MCV 104 fL), WBC 22×10⁹/L, Platelets 180×10⁹/L
INR 1.8, aPTT 42 seconds
Albumin 24 g/L

Examiner: What micronutrient deficiencies are you concerned about in this patient, and what is your immediate management?

Candidate: This patient has multiple risk factors for micronutrient deficiencies including chronic alcohol use disorder, prolonged reduced oral intake, malnutrition, and critical illness from severe septic shock.

My immediate concerns are:

Thiamine deficiency: The persistent lactic acidosis (9.5 mmol/L) despite what I assume has been adequate resuscitation, combined with chronic alcohol use and malnutrition, strongly suggests thiamine deficiency. I would give thiamine 200-300 mg IV immediately before any dextrose-containing fluids to prevent precipitating Wernicke encephalopathy.
Electrolyte deficiencies (magnesium, phosphate, potassium, calcium): The patient has severe hypomagnesemia (0.4 mmol/L), hypophosphatemia (0.5 mmol/L), hypokalemia (3.2 mmol/L), and hypocalcemia (ionized Ca 0.9 mmol/L). These need urgent correction:
- Magnesium sulfate 2-4 g IV over 15-30 minutes
- Potassium chloride 20-40 mmol IV (rate 10 mmol/hour with cardiac monitoring)
- Calcium gluconate 1-2 g IV over 10-20 minutes
- Phosphate 0.16-0.32 mmol/kg IV over 6-12 hours
Vitamin K deficiency: The elevated INR (1.8) in the context of malnutrition, probable antibiotic use, and sepsis suggests vitamin K deficiency. I would give vitamin K 5-10 mg IV slow infusion.
Folate/B12 deficiency: The macrocytic anemia (MCV 104 fL) suggests possible folate or B12 deficiency. I would send serum B12 and folate levels and consider supplementation.

Examiner: Good. Explain the pathophysiology of thiamine deficiency causing lactic acidosis in this patient.

Candidate: Thiamine (vitamin B1) is an essential cofactor in carbohydrate metabolism, specifically for the pyruvate dehydrogenase (PDH) complex, which converts pyruvate to acetyl-CoA for entry into the Krebs cycle.

In thiamine deficiency, the PDH complex cannot function. Pyruvate cannot enter aerobic metabolism and is instead shunted via lactate dehydrogenase to lactate, producing "Type B" lactic acidosis - lactic acidosis in the presence of adequate tissue oxygenation and perfusion.

This patient's persistent lactic acidosis despite (I assume) adequate fluid resuscitation, MAP, and ScvO₂ suggests a metabolic cause rather than tissue hypoperfusion (Type A lactic acidosis). Thiamine deficiency is a reversible cause and must be treated empirically in high-risk patients.

Thiamine is also a cofactor for α-ketoglutarate dehydrogenase in the Krebs cycle and transketolase in the pentose phosphate pathway, so deficiency impairs overall cellular energy production.

Examiner: Why do you give thiamine BEFORE dextrose-containing fluids?

Candidate: Administering dextrose (carbohydrate load) in a thiamine-deficient patient can precipitate acute Wernicke encephalopathy. Here's why:

When glucose is given, there is a surge in metabolic demand for thiamine to process the glucose via the PDH complex and Krebs cycle. In a patient with marginal or depleted thiamine stores, this glucose load rapidly exhausts any remaining thiamine, particularly in metabolically active tissues like the brain.

The mammillary bodies, thalamus, and periaqueductal gray matter are particularly vulnerable, leading to the acute neurological syndrome of Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia).

If untreated, Wernicke encephalopathy can progress to irreversible Korsakoff psychosis (chronic amnesia, confabulation, apathy) in 80% of cases. Mortality is 10-20% if untreated.

Therefore, in any at-risk patient (chronic alcohol use, malnutrition, unexplained lactic acidosis), we give thiamine 200-300 mg IV BEFORE dextrose to prevent this complication. Thiamine is extremely safe even in high doses, so we treat empirically rather than waiting for confirmatory testing.

Examiner: On day 3, the patient is stabilized and you plan to start enteral nutrition via nasojejunal tube. What is your refeeding syndrome prevention strategy?

Candidate: This patient is at very high risk for refeeding syndrome due to chronic alcohol use, prolonged reduced oral intake (2 weeks), malnutrition, and critical illness. My prevention strategy includes:

Pre-Feeding Interventions:

Continue thiamine supplementation: Thiamine 200-300 mg IV daily BEFORE and during nutrition initiation to prevent Wernicke encephalopathy and lactic acidosis
Correct electrolyte abnormalities BEFORE starting nutrition:
- Target phosphate >0.65 mmol/L (currently 0.5 mmol/L - needs supplementation)
- Target magnesium >0.5 mmol/L (currently 0.4 mmol/L - needs supplementation)
- Target potassium >3.5 mmol/L (currently 3.2 mmol/L - needs supplementation)

Nutrition Initiation Protocol:

"Start low, go slow":
- Estimate energy requirements: 25-30 kcal/kg/day (approximately 1,500-1,800 kcal/day assuming ~60 kg)
- Start at 10-20 kcal/kg/day (600-1,200 kcal/day) on day 1 (≤50% of target)
- Increase by 20% every 2-3 days to reach target by days 5-7
Protein: Start at 1.2-1.5 g/kg/day (protein does NOT trigger refeeding and should not be restricted)

Monitoring Plan:

Electrolytes: Phosphate, magnesium, potassium, sodium, glucose - daily × 5-7 days after starting nutrition
If hypophosphatemia develops (PO₄ <0.65 mmol/L): REDUCE caloric intake to 20 kcal/hour × 48 hours while correcting electrolytes (REFEED Trial protocol)
Clinical monitoring: Fluid balance, cardiovascular status (arrhythmias, heart failure), neurological status (Wernicke signs)
Supplementation: Continue thiamine, magnesium, phosphate, potassium supplementation as needed

Examiner: Excellent. On day 5, the patient develops new-onset atrial fibrillation with rapid ventricular response (HR 145 bpm). Magnesium is 0.6 mmol/L. How do you manage this?

Candidate: New-onset atrial fibrillation in the ICU with hypomagnesemia is a common scenario. Hypomagnesemia is an independent risk factor for arrhythmias, including atrial fibrillation, and must be corrected urgently.

Immediate Management:

Magnesium supplementation:
- Magnesium sulfate 2-4 g IV (8-16 mmol) over 15-30 minutes
- Target magnesium >0.8 mmol/L (some sources recommend >1.0 mmol/L for arrhythmia suppression)
- Recheck magnesium 2-4 hours after supplementation
Rate control:
- If hemodynamically stable: Beta-blocker (metoprolol 2.5-5 mg IV boluses) or calcium channel blocker (diltiazem 0.25 mg/kg IV over 2 minutes)
- If hemodynamically unstable: Synchronized DC cardioversion (120-200 J biphasic)
Anticoagulation: Initiate anticoagulation (unfractionated heparin infusion or LMWH) if no contraindications, given new-onset AF
Correct other electrolyte abnormalities:
- Hypokalemia (target K⁺ >4.0 mmol/L for arrhythmia suppression)
- Hypocalcemia (magnesium deficiency often prevents calcium correction, so magnesium must be corrected first)
Identify and treat precipitants:
- Sepsis, pain, hypoxia, hypercarbia, fluid overload, myocardial ischemia, alcohol withdrawal

Follow-Up:

Continue magnesium supplementation (magnesium oxide 400 mg oral TID or magnesium sulfate 1-2 g IV q12h) until consistently >0.8 mmol/L
Monitor magnesium daily in ICU, especially with ongoing losses (diuretics, CRRT, diarrhea)

Examiner: Good. What other micronutrient deficiencies would you consider investigating in this patient if she has prolonged ICU stay?

Candidate: If this patient has a prolonged ICU stay, I would consider investigating and supplementing the following micronutrients:

Vitamin D (25-Hydroxyvitamin D):
- Deficiency is present in 40-80% of ICU patients and associated with increased mortality, longer ICU stay, and higher infection risk
- I would check 25(OH)D levels at baseline and supplement if deficient (<50 nmol/L)
- Standard replacement (1,000-2,000 IU daily) rather than high-dose (VITdAL-ICU and VIOLET trials showed no mortality benefit with high-dose)
Zinc:
- Hypozincemia common in critical illness due to redistribution and increased losses
- Important for wound healing, immune function, and recovery
- Check plasma zinc; supplement with zinc sulfate 220 mg PO TID (50 mg elemental zinc) or 22-45 mg IV daily if deficient
Selenium:
- Deficiency in 40-60% of septic patients
- Antioxidant and immunomodulatory roles via selenoproteins
- Check plasma selenium; supplementation 500-1,000 mcg IV loading then 500 mcg IV daily × 10-14 days if deficient (though routine supplementation not recommended per Cochrane review)
Trace elements (copper, manganese, chromium, molybdenum):
- If prolonged parenteral nutrition (>7 days), ensure standard trace element solution is added to TPN
- Check copper levels if prolonged TPN or high zinc supplementation (zinc antagonizes copper absorption)
Vitamin C:
- Depletion common in sepsis due to oxidative stress
- Standard supplementation (100-200 mg/day) reasonable to prevent deficiency
- High-dose vitamin C (>3 g/day) NOT recommended (LOVIT trial showed harm)
Vitamin B12 and folate:
- Already identified as potential deficiency (macrocytic anemia)
- Check levels and supplement as needed
Vitamin K:
- Already identified (elevated INR)
- Continue vitamin K supplementation (5-10 mg oral/IV weekly) if prolonged antibiotics or malnutrition

Viva Scenario 2: Micronutrient Toxicity and Monitoring (20 marks)

Scenario: You are the ICU consultant on ward round. A 68-year-old man has been in ICU for 4 weeks following severe COVID-19 ARDS. He has been on prolonged parenteral nutrition supplemented with high-dose vitamin D (50,000 IU daily), vitamin C (3 g IV q6h), and selenium (1,000 mcg IV daily) as per a "COVID-19 cocktail" protocol initiated by the previous covering consultant.

Current Investigations:

Calcium (corrected) 3.2 mmol/L (normal 2.1-2.6)
Phosphate 1.8 mmol/L (normal 0.8-1.5)
AKI: Creatinine 250 μmol/L (baseline 80 μmol/L)
Patient complaining of nausea, confusion, polyuria

Examiner: What is your immediate assessment and management?

Candidate: This patient has severe hypercalcemia (3.2 mmol/L) with associated AKI, nausea, confusion, and polyuria. The most likely cause is vitamin D toxicity (hypervitaminosis D) from the high-dose vitamin D supplementation (50,000 IU daily for 4 weeks).

Chronic high-dose vitamin D (>10,000 IU/day) causes hypercalcemia, nephrocalcinosis, and renal failure. This patient has been receiving 50,000 IU daily for 4 weeks - a total cumulative dose of 1.4 million IU, which is well above toxic levels.

Immediate Management:

Stop all vitamin D supplementation immediately
Treat severe hypercalcemia (calcium >3.0 mmol/L):
- IV fluids: 0.9% normal saline 200-300 mL/hour to restore euvolemia and promote calciuresis (target urine output 100-150 mL/hour)
- Calcitonin: 4-8 IU/kg IM/SC q12h (rapid onset within 4-6 hours, but short-lived effect; reduces calcium by 0.5-1.5 mmol/L)
- Bisphosphonates: Zoledronic acid 4 mg IV over 15-30 minutes OR pamidronate 60-90 mg IV over 2-4 hours (slower onset 2-4 days, but sustained effect for weeks)
- Hemodialysis: If refractory hypercalcemia or severe AKI, consider urgent hemodialysis with low-calcium dialysate
Monitor:
- Calcium (ionized and corrected) q4-6h initially, then q12h
- Renal function (creatinine, urea, electrolytes) daily
- ECG (shortened QT interval, arrhythmias)
- Neurological status (confusion can progress to coma)
Investigate vitamin D toxicity:
- Check 25-hydroxyvitamin D level (likely >250 nmol/L, >100 ng/mL)
- Check PTH (should be suppressed in hypercalcemia of vitamin D toxicity)

Examiner: Good. The patient is also receiving high-dose selenium (1,000 mcg IV daily). What toxicity concerns do you have?

Candidate: High-dose selenium (1,000 mcg IV daily for 4 weeks) significantly exceeds the RDA (55 mcg/day) and the upper tolerable limit (400 mcg/day). This patient is at high risk for selenium toxicity (selenosis).

Clinical Features of Selenosis:

Garlic breath odour (volatile selenium compounds exhaled)
Metallic taste in mouth
Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain
Hair and nail changes: Alopecia, nail brittleness, nail loss
Neurological: Peripheral neuropathy, tremor, irritability, fatigue
Dermatological: Dermatitis, skin lesions

Management:

Stop selenium supplementation immediately
Check plasma selenium level (toxic if >1,000 μg/L; normal range 70-150 μg/L)
Supportive care: Hydration, electrolyte management, symptomatic treatment for nausea
Monitor for neurological symptoms (peripheral neuropathy can be irreversible if severe)

Key Point: The Cochrane review (2015) showed NO mortality benefit for selenium supplementation in critically ill patients. Routine high-dose selenium is NOT recommended and carries significant toxicity risk.

Examiner: The patient has also been receiving high-dose vitamin C (3 g IV q6h, total 12 g/day). What evidence do you know about high-dose vitamin C in critical illness?

Candidate: There have been several major trials investigating high-dose vitamin C in sepsis and critical illness, with conflicting results:

CITRIS-ALI Trial (2019, PMID 30625275):

Vitamin C 50 mg/kg IV q6h vs placebo in sepsis-induced ARDS
Primary outcome: No improvement in organ dysfunction scores (SOFA)
Secondary outcome: Lower 28-day mortality with vitamin C (29.8% vs 46.3%, p=0.03)
Interpretation: Suggestive of benefit but underpowered for mortality

VITAMINS Trial (2020, PMID 31577396):

Vitamin C 1.5 g IV q6h + thiamine + hydrocortisone vs hydrocortisone alone in septic shock
Primary outcome: No difference in time alive and free of vasopressors (median 122 vs 125 hours, p=0.83)
No mortality benefit
Interpretation: The "metabolic resuscitation cocktail" does NOT improve outcomes

LOVIT Trial (2022, PMID 35939567):

Vitamin C 50 mg/kg IV q6h vs placebo in septic shock
Primary outcome: HIGHER mortality/persistent organ dysfunction with vitamin C (50.1% vs 43.6%, p=0.03)
Higher 28-day mortality (44.5% vs 38.5%, p=0.09)
Interpretation: High-dose vitamin C may be HARMFUL in septic shock

Current Consensus (Surviving Sepsis Campaign 2021):

Routine high-dose vitamin C (>3 g/day) NOT recommended in sepsis
Standard supplementation (100-200 mg/day) reasonable to prevent deficiency

In this patient:

I would STOP the high-dose vitamin C (12 g/day)
Continue standard supplementation (100-200 mg/day) in parenteral nutrition
No evidence of benefit and potential for harm

Examiner: Excellent. The patient has been on parenteral nutrition for 4 weeks. What trace element monitoring and supplementation would you ensure?

Candidate: For patients on prolonged parenteral nutrition (>7 days), trace element supplementation and monitoring are essential to prevent deficiencies and toxicities.

Standard Trace Element Supplementation in TPN:

Zinc: 2.5-5 mg elemental zinc daily (higher in high GI losses: 12-17 mg/day)
Copper: 0.3-0.5 mg elemental copper daily
Selenium: 60-100 mcg daily
Manganese: 60-100 mcg daily (OMIT in cholestasis due to biliary excretion and risk of toxicity)
Chromium: 10-15 mcg daily
Molybdenum: 20-40 mcg daily

These are typically provided in commercially available trace element solutions added to TPN.

Monitoring Strategy:

At Baseline (before starting TPN):

Zinc, copper, selenium levels
Liver function tests (baseline for monitoring manganese toxicity risk)

During Prolonged TPN (>4 weeks):

Zinc: q2-4 weeks (deficiency common with GI losses, diarrhea, fistulas)
Copper: q4 weeks (monitor for deficiency, especially if high zinc supplementation; copper deficiency causes anemia, neutropenia, myeloneuropathy)
Selenium: q4 weeks
Manganese: Monitor liver function; if cholestasis develops, STOP manganese (risk of neurotoxicity/parkinsonism)

Other Micronutrients in Prolonged TPN:

Thiamine, folate, B12: q4-6 weeks (water-soluble vitamins)
Vitamin D: q4-6 weeks (fat-soluble vitamin)
Vitamin K: Monitor INR weekly (provided in TPN but may be insufficient in cholestasis or antibiotic use)

In this patient (4 weeks TPN):

Check zinc, copper, selenium, B12, folate, vitamin D levels now
Ensure standard trace element solution is added to TPN (not the toxic high-dose selenium)
Correct any documented deficiencies

Examiner: Finally, if this patient were an Aboriginal Australian from a remote community in the Northern Territory, what additional micronutrient considerations would you have?

Candidate: Aboriginal and Torres Strait Islander peoples from remote communities have specific micronutrient considerations due to socioeconomic factors, chronic disease burden, and cultural factors.

Higher Prevalence of Micronutrient Deficiencies:

Vitamin D: Despite high sun exposure, vitamin D deficiency is common (30-60% prevalence) due to:
- Skin pigmentation (reduced vitamin D synthesis)
- Cultural clothing practices
- Indoor occupations in some settings
- Limited access to vitamin D-fortified foods in remote areas
Iron: Higher prevalence of iron deficiency due to:
- Chronic disease burden (diabetes, CKD)
- Dietary factors (limited access to iron-rich foods)
- Hookworm infection in some remote tropical areas
Zinc: Common in chronic kidney disease and diabetes (both higher prevalence in Aboriginal populations)
Folate: Lower intake of folate-rich foods (fresh vegetables) in remote communities due to cost, access, and food deserts

Chronic Disease Burden:

Diabetes: 3-4× higher prevalence → increased risk of vitamin D, B12, zinc deficiencies
Chronic kidney disease: 2-3× higher prevalence → vitamin D, iron, erythropoietin deficiencies
Cardiovascular disease: Higher rates → folate, B12 deficiencies (hyperhomocysteinemia)

Food Insecurity and Access:

Remote communities: Limited access to fresh fruit/vegetables (vitamin C, folate)
High cost of nutritious food → reliance on processed/canned foods
Traditional bush foods (kangaroo, witchetty grubs, bush tomatoes) rich in micronutrients but reduced consumption

Cultural Considerations:

Involve Aboriginal Health Workers (AHW) in nutrition counseling and education about micronutrient supplementation
Family-centered decision-making: Include family and Elders in nutrition care plans
Culturally appropriate communication: Use yarning (conversational storytelling), visual aids, and plain language
Barriers to supplement adherence: Literacy (medication labels), cost (limited PBS access in some remote areas), medication complexity (polypharmacy common)

Remote ICU/Retrieval Considerations:

Royal Flying Doctor Service (RFDS) retrievals: Empiric thiamine 200-300 mg IV before dextrose in suspected malnutrition
Telehealth support: Remote ICUs may lack on-site micronutrient testing; use clinical judgment and empiric supplementation
Medicare-funded testing: 25(OH)D testing is PBS-funded for Aboriginal and Torres Strait Islander peoples ≥50 years

Specific Actions for This Patient:

Check vitamin D, iron studies, B12, folate at baseline
Supplement empirically given high-risk population
Involve AHW for nutrition education and discharge planning
Ensure culturally safe communication with patient and family
Coordinate with remote health service for ongoing micronutrient monitoring post-discharge

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Clinical board

Urgent signals

Exam focus

Linked comparisons

Editorial and exam context

Micronutrient Deficiencies in Critical Care

Clinical Overview

Epidemiology and Risk Factors

Prevalence in Critical Illness

Risk Factors for Micronutrient Deficiencies in ICU

Pathophysiology

Thiamine (Vitamin B1)

Vitamin D (Cholecalciferol and Ergocalciferol)

Vitamin C (Ascorbic Acid)

Selenium

Zinc

Vitamin B12 (Cobalamin) and Folate

Vitamin K

Trace Elements (Copper, Manganese, Chromium, Molybdenum)

Electrolytes as Micronutrients

Clinical Presentation and Diagnosis

Thiamine Deficiency

Vitamin D Deficiency

Vitamin C Deficiency

Selenium Deficiency

Zinc Deficiency

Vitamin B12 and Folate Deficiency

Vitamin K Deficiency

Management and Supplementation Protocols

Thiamine Supplementation

Vitamin D Supplementation

Vitamin C Supplementation

Selenium Supplementation

Zinc Supplementation

Vitamin B12 and Folate Supplementation

Vitamin K Supplementation

Trace Elements (Copper, Manganese, Chromium, Molybdenum)

Electrolytes (Magnesium, Phosphate, Calcium)

Monitoring Strategies

Routine ICU Micronutrient Monitoring

Laboratory Parameters and Targets

Complications and Toxicity

Hypervitaminosis and Toxicity

Refeeding Syndrome

Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples

Māori Health (New Zealand)

Australian and New Zealand Context

TGA-Approved Micronutrient Supplements

PBS Coverage and Restrictions

ANZICS Guidelines and Recommendations

Evidence Summary and Key Trials

Thiamine Trials

Vitamin D Trials

Vitamin C Trials

Selenium Trials

Phosphate and Refeeding Syndrome Trials

Vitamin K and Warfarin Reversal Trials

Assessment Content

SAQ Practice Question 1: Thiamine Deficiency and Lactic Acidosis (15 marks)

SAQ Practice Question 2: Refeeding Syndrome and Micronutrient Monitoring (15 marks)

Viva Scenario 1: Comprehensive Micronutrient Management in Critical Illness (20 marks)

Viva Scenario 2: Micronutrient Toxicity and Monitoring (20 marks)

References

Learning map

Prerequisites

Differentials

Consequences