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Electrolyte Management in ICU

Identify Immediately Life-Threatening Electrolyte Abnormalities

• Consider causes and ongoing causative factors needing management

Replace Potentially Significant Deficits of Critical Ions

• K⁺ < 3.5 mmol/L
  • Risk: Arrhythmia
• Mg²⁺ < 0.8 mmol/L
  • Risk: Arrhythmia
• PO₄^3- < 0.7 mmol/L
  • Risk: Respiratory muscle weakness
• Na⁺ < 125 mmol/L
  • Risk: Cerebral dysfunction
• Ca²⁺ (Ionized) < 0.8 mmol/L
  • Risk: Hypotension

Manage Potentially Significant Elevations of Critical Ions

• K⁺ > 5.5 mmol/L with ECG changes
• Na⁺ > 160 mmol/L
• Cl^– > 130 mmol/L
• PO₄^3- > 2.5 mmol/L
• Mg²⁺ > 4.0 mmol/L

Consider Fluid-Conservative Methods of Intravenous Replacement for Deficits

Pure K⁺ Replacement

• Dosage:
  • 80 meq (40 mL) 15% KCl in a total volume of 200 mL (mix with 160 mL of either 0.9% NaCl or D5W) over 4 hours (50 mL/hr)
  • ONLY THROUGH CENTRAL LINE VIA INFUSION PUMP
  • Maximum rate of replacement = 20 meq K⁺ per hour

Pure Mg²⁺ Replacement

• Dosage:
  • 4g MgSO₄ in 50 mL total volume (mix with 42 mL 0.9% NaCl or D5W in buretrol) over 15 minutes

K⁺ & Mg²⁺ Replacement

• Dosage:
  • 80 meq (40 mL) 15% KCl + 4g MgSO₄ in a total volume of 200 mL (mix with 152 mL of either 0.9% NaCl or D5W) over 4 hours (50 mL/hr)
  • ONLY THROUGH CENTRAL LINE VIA INFUSION PUMP

Pure PO₄^3- Replacement

• Dosage:
  • 40 meq (20 mL) KPO₄ in a total volume of 200 mL (mix with 180 mL of either 0.9% NaCl or D5W) over 4 hours (50 mL/hr)
  • ONLY THROUGH CENTRAL LINE VIA INFUSION PUMP
  • Never give more than 10 meq KPO₄ per hour–Risk of hypocalcemia

K⁺ & PO₄^3- Replacement

• Dosage:
  • 40 meq (20 mL) KPO₄ + 40 meq (20 mL) 15% KCl in a total volume of 200 mL (mix with 160 mL of either 0.9% NaCl or D5W) over 4 hours (50 mL/hr)
  • ONLY THROUGH CENTRAL LINE VIA INFUSION PUMP
  • Infusion rate limitations of both K⁺ and PO₄^3- apply

Mixing Guidelines

• DO NOT MIX MgSO₄ with KPO₄ in the same bag.

Non-Emergent Ca²⁺ Replacement for Low Ionized Calcium without Emergent Symptoms

• Dosage:
  • 10 mL 10% Calcium gluconate in 50 mL total volume (mix with 40 mL 0.9% NaCl or D5W in buretrol) over 10 minutes
  • Re-evaluate ionized Ca²⁺ 10 minutes after infusion
  • Avoiding stopping for arrhythmias during infusion

Hyponatremia

• Defined as: Na⁺ < 135 mmol/L
• Correction:
  • Specific correction only required for Na⁺ < 120 mmol/L with neurological symptoms
  • Correct at no more than 1 mmol/L/hr to 120 mmol/L using 0.9% NaCl if patient is intravascularly volume depleted
  • Hypertonic saline if patient is intravascularly replete or overloaded–Consult specific guidelines for dosage calculation

Hypernatremia

• Severity:
  • Likely requires active management when > 155 mmol/L
• Management:
  • Decide on patient’s fluid volume status as this will influence the choice of corrective management
  • Fluid overload + hypernatremia suggests total body sodium overload (e.g., iatrogenic administration)
  • Fluid underload + hypernatremia suggests dehydration and hence concentration of sodium

Hyperkalemia

• Factors Influencing Urgency of Treatment:
  • Acute (less than 2 days) or chronic?
  • Associated with ECG changes?
    • Acute hyperkalemia with ECG changes warrants urgent therapy
• Likely Cause:
  • Increased intake? (Often iatrogenic)
  • Decreased elimination from body (renal failure commonly)
  • Normal total body potassium but intracellular → extracellular shift (e.g., acute acidosis)
• Management:
  • Elimination of Excess K⁺ from the Body:
    • Dialysis [fast] / Diuresis / “Kayexalate” [slow]
  • Shifting K⁺ Extracellularly → Intracellularly:
    • Dextrose + Insulin
    • Beta₂ agonists
      • Inhaled
      • Intravenous
  • Antagonizing K⁺ Effect on Myocardium:
    • Broad QRS: Controlled Calcium gluconate infusion
    • Hyperkalemic cardiac arrest: Calc₂ 1000 mg IVI stat

Hyperchloremia

• Often iatrogenic, may contribute to metabolic acidosis.

Fluid Management in ICU

Post-Resuscitation Fluid Strategy

• Appropriate Fluid Strategy:
  • Excessive fluids may be as lethal as inadequate fluids (just on a longer timescale).

Haemodynamic Stability

• Haemodynamic Unstability:
  • Ensure intravascular volume deficit is identified and corrected aggressively as described in “Circulation” above.

Diabetic Emergency

• Manage according to diabetic emergencies protocols.

Fluid Infusion Planning Post-Stabilization

• Maintenance Requirements:
  • Fluids
  • Electrolytes and nutrition
• Fluid Requirement Phases:
  • Resuscitation:
    • Still unstable with ongoing absolute/relative intravascular hypovolaemia, or need for active fluid replacement.
    • Expect need to augment Total Body Water.
    • A positive fluid balance is expected.
  • Plateau:
    • Inflammatory response has settled; no additional fluids needed.
    • Fluid administration should match baseline maintenance.
    • Keep Total Body Water at current level.
    • A daily neutral fluid balance is desired.
  • De-Resuscitation:
    • Patient is recuperating; Total Body Water is greater-than-healthy-baseline.
    • Fluids need elimination to return the patient to pre-illness levels.
    • A daily negative fluid balance is desired.

Resuscitation Phase Considerations

• Rehydrating Dehydrated Tissues:
  • Blood losses?
  • Plasma losses (e.g., open abdomen suction, open wounds seeping into dressings)?
  • Abnormal nasogastric losses?
  • Other abnormal GIT losses?
  • Inappropriate urine losses (e.g., polyuric renal failure with tubule dysfunction)?
• Unquantifiable Ongoing Losses:
  • “Capillary leak” (endothelial and glycocalyx malfunction) in inflammatory states with sequestration into tissues.
  • Mechanisms to detect “fallen behind” and the need for bolus fluids.
  • Mechanisms to detect fluid overload.
  • Balance of vasopressors and fluids in inflammatory states.

Plateau Phase Considerations

• Markers to Confirm Plateau Phase:
  • Limits of allowable positivity or negativity of fluid balance before active management is required.
  • Managing fluid administration to meet nutritional goals without exceeding fluid limit.

De-Resuscitation Phase Considerations

• Spontaneous De-Resuscitation:
  • Need for assisted de-resuscitation?
  • Issues: Tissue oedema? Lung compliance? Oxygenation issues? Gut oedema?
• Assisted De-Resuscitation:
  • Best route: Dialysis? Diuresis?
    • Furosemide Boluses:
      • Regular?
      • P.R.N.?
    • Furosemide Infusion:
      • Furosemide infusion + acetazolamide to control contraction alkalosis.
• Achievable Negative Fluid Balance:
  • Is it being achieved? Does the de-resuscitation plan need augmentation?

Default Baseline Fluid Volume

• Adults: 1 mL/kg (actual mass) per hour.
  • Includes all medications, infusions, feeds.
  • Adjust for bolus medications:
    • 200 mL of antibiotics given 8 hourly = 25 mL/hr.
  • Adjust for feed volume increases:
    • By de-resuscitation phase, only nutrition and dissolution volumes required.

Post-Admission Intravenous Fluids

• Crystalloids:
  • Colloid fluids should only be used for bolus replacement of acute identified intravascular volume deficit and never be given by infusion.
• Phases:
  • Resuscitation Phase (Haemodynamically Unstable):
    • Head Injury Moderate/Severe:
      • Normal Saline (0.9% NaCl)
    • No Head Injury:
      • Ringer’s Lactate or equivalent
  • Resuscitation Phase (No Longer Haemodynamically Unstable but Replacing Losses or Rehydrating Tissues):
    • Head Injury Moderate/Severe:
      • Normal Saline (0.9% NaCl) unless Na⁺ > 145 mmol/L or Cl^– > 115 mmol/L
    • Plasma-like Losses:
      • Ringer’s Lactate or equivalent
    • Rehydration of Tissues/Polyuria Losses/Some NG Losses:
      • 0.45% NaCl but check U&E frequently and adapt.
  • Plateau Phase (Non-Head Injury):
    • 0.45% NaCl + 5% Dextrose (“Rehydration Solution”)
      • NB: Has no K⁺
    • 5% Mainteyte
      • Not if plasma Na⁺ < 125 mmol/L or K⁺ > 5.0 mmol/L.
• Fluid Rate Limits:
  • Do not exceed 1.5 mL/kg/hr.
  • If more is needed, patient is not in Plateau phase.
  • Dextrose-containing fluids exceeding 1.5 mL/kg/hr may cause uncontrolled hyperglycaemia.
• Special Cases:
  • Elevated intracranial pressure: Avoid hypotonic fluids; consult with reference to U&E.
• Fluid Choice Adjustment:
  • Re-evaluate and adjust frequently based on trends in U&E and clinical evaluation.

Feed Volume and Baseline Fluid Volume

• Feed Volume Increases:
  • By de-resuscitation phase, only nutrition and dissolution volumes needed.
• Elevated Baseline Infusion of Crystalloids:
  • Convenient for tissue rehydration or ongoing losses.
  • Set formal target for total fluids (e.g., 1.5/2/3 mL/kg/hr) based on clinical judgment.
  • Subtract volumes of given medication, infusions, feeds.
  • Administer appropriate colloid as needed to “make up the difference”.
  • Avoid glucose-containing fluids for elevated rate infusions.
• Review Baseline Infusion:
  • At least every 4 hours to avoid overload.

Quantifiable Ongoing Losses

• Replacing Ongoing Losses:
  • Loss rates can change; aim low in setting replacement fluid rates.
  • Replacement rate (4-hourly) advised.
  • “Top-up boluses” as needed.

Large Volume Fluid Infusion

• Haematological Effects:
  • Dilutional anaemia?
  • Dilutional coagulopathy?
  • Abnormal fluid losses due to endothelial-glycocalyx function impairment, sequestration into tissues.
  • Consideration of “non-leakable” packed red blood cells.

Blood Management in ICU

Ensure Adequate Haemoglobin to Allow Adequate DO₂

Haemoglobin (Hb) Target According to Patient Condition

Hb = 10 g/dL

• Indications:
  • Acutely shocked, especially septic shock with evidence of tissue hypoperfusion.
  • Acute coronary syndromes.
  • Strong history of ischaemic heart disease.
  • Post free flap.
  • Other identified ischaemic tissue.

Hb = 8.5 g/dL

• Indications:
  • Not shocked, but ongoing significant blood loss likely.
  • Ongoing fluid or inotrope/vasopressor infusions required to maintain haemodynamic stabilization.
  • Elderly/frail/malnourished patients with ongoing organ dysfunction.
  • Patient symptomatically anaemic at Hb 7.0 g/dL.

Hb = 7.0 g/dL

• Indications:
  • Haemodynamically stable: no inotrope/vasopressor requirements.
  • No ongoing blood loss/expected blood loss.
    • Includes controlled upper GIT bleed.
  • Not symptomatically anaemic, no evidence of organ dysfunction.

Note

• Transfused Blood:
  • May not be fully functional for oxygen carriage for up to 24 hours post-administration.
  • Risks:
    • May not leak from vessels in severe endothelial-glycocalyx dysfunction.
    • May increase blood viscosity, leading to greater endothelial stimulation, increased vasoconstrictive endothelin production, and increased vascular tone in vasodilated patients who are also anaemic.

Body Compartments

Fluid Compartments

Compartment	Fluid as Percent Body Weight (%)	Total Body Water (%)	Fluid Volume (L)
Intracellular	40	67	28
Extracellular
– Interstitial	15	25	10.5
– Intravascular	5	8	3.5
Total	60	100	42

Electrolyte Concentrations

Electrolyte	Gram-Molecular Weight	Intracellular (mEq/L)	Extracellular (mEq/L)
			Intravascular
Sodium	23.0	10	145
Potassium	39.1	140	4
Calcium	40.1	<1	3
Magnesium	24.3	50	2
Chloride	35.5	4	105
Bicarbonate	61.0	10	24
Phosphorus	31.01	75	2
Protein (g/dL)		16	7

Intracellular Fluid

• Sodium-Potassium Pump: A membrane-bound adenosine triphosphate (ATP)–dependent pump exchanges Na⁺ for K⁺ in a 3:2 ratio.
• Ion Concentration: Cell membranes are relatively impermeable to sodium and, to a lesser extent, potassium ions. Thus, potassium is concentrated intracellularly, whereas sodium is concentrated extracellularly.
• Osmotic Pressure:
  • Potassium is the most important determinant of intracellular osmotic pressure.
  • Sodium is the most important determinant of extracellular osmotic pressure.
• Protein Impermeability: The impermeability of cell membranes to most proteins results in a high intracellular protein concentration. Proteins act as non-diffusible solutes (anions), and the unequal exchange ratio of 3 Na⁺ for 2 K⁺ by the cell membrane pump prevents relative intracellular hyperosmolality.
• Cell Swelling: Interference with Na⁺–K⁺-ATPase activity, as occurs during ischemia or hypoxia, results in progressive swelling of cells.

Extracellular Fluid

• Primary Function: The principal function of extracellular fluid (ECF) is to provide a medium for the delivery of cell nutrients and electrolytes and the removal of cellular waste products.
• Sodium’s Role:
  • Sodium is the most important extracellular cation.
  • It is the major determinant of extracellular osmotic pressure and volume.
  • Changes in ECF volume are therefore related to changes in total body sodium content.

Volume Regulation Vs Osmoregulation

Aspect	Volume Regulation	Osmoregulation
Purpose	Control extracellular volume	Control extracellular osmolality
Mechanism	Vary renal Na+ excretion	Vary water intake, renal water excretion
Sensors	Afferent renal arterioles	Hypothalamic osmoreceptors
	Carotid baroreceptors
	Atrial stretch receptors
Effectors	Renin-angiotensin-aldosterone	Thirst
	Sympathetic nervous system	Antidiuretic hormone
	Tubuloglomerular balance
	Renal pressure natriuresis
	Atrial natriuretic peptide
	Antidiuretic hormone
	Brain natriuretic peptide

Electrolytes

Summary of Effects of Excess and Deficits of Electrolytes

Electrolyte	Values (mmol/L)	Effect of Excess	Effect of Deficit
Cations
Sodium	136–145	Cerebral hemorrhage, venous thrombosis, altered mental status, seizures, coma. Cerebral edema if corrected too quickly	Neuromuscular excitability (e.g., hyperreflexia), altered mental status, lethargy, irritability, seizures, coma. Demyelination syndromes if corrected too quickly
Potassium	3.5–5.0	Peaked T-waves, widened QRS, ventricular arrhythmias, cardiac arrest. Flaccid paralysis (especially in hyperkalemic familial periodic paralysis)	Depressed ST segments, biphasic T-waves, prominent U-waves/tachyarrhythmias. Muscle weakness, tetany, cramping, rhabdomyolysis, ileus, respiratory failure, polyuria with secondary polydipsia
Calcium	Total: 2.10–2.60, Ionized: 1.10–1.35	Neurological (headache, fatigue, apathy, confusion), gastrointestinal (pain, constipation, vomiting), renal (polyuria, nephrolithiasis, renal failure), cardiovascular (arrhythmias, short QT interval, AV or bundle branch block), skeletal (pain, arthralgia)	Tetany, diffuse encephalopathy, seizures, hyperreflexia, laryngospasm, dehydration secondary to hypercalcemic nephrogenic diabetes insipidus
Magnesium	0.6–1.2	Prolonged PR interval, widened QRS, hyporeflexia, respiratory depression, cardiac arrest	Muscle weakness, tetany, hyperreflexia, seizures, cardiac arrhythmias. Often associated with hypocalcemia and hypokalemia
Anions
Chloride	95–105	Possible acute renal impairment	Unknown/related to associated abnormality
Phosphate	0.8–1.5	Symptoms of acute hypocalcemia, acute tubular necrosis, ectopic calcification	Below 0.32 mmol/L: respiratory muscle dysfunction, left shift of oxyhemoglobin dissociation curve, myocardial dysfunction, arrhythmias, myopathy, encephalopathy, irritability, seizures, coma, rhabdomyolysis, hemolytic anemia

Sodium

Hypernatremia

Summary

Correction of Hypernatremia (Total Body Water Deficit)

Calculation Steps

1. Normal Total Body Water (TBW)
   Normal TBW = 0.6X weight (kg) (0.5 in female)
2. Present TBW (with high sodium)
   Present TBW = (Normal TBW x 140)/Patient’s current sodium
3. Water Deficit
   Water Deficit = Normal TBW – Present TBW
4. Fluid Replacement Rate
   • Replace the calculated water deficit over 48 hours.
   • Convert the water deficit to milliliters per hour.

Example Calculation

For a 70 kg male patient with a sodium level of 160 mmol/L:

1. Normal TBW: (0.6 \times 70 = 42 ) liters.
2. Present TBW: (42x 140)/160 = 36.75 liters.
3. Water Deficit: (42 – 36.75) = 5.25 liters.
4. Fluid Replacement Rate: 5250/ 48 hours= 109.375ml/hour

Anaesthesia Considerations for Hypernatremia

Elective Surgeries

• Postpone Surgery: If sodium > 150-155 mmol/L.
• Identify Cause: Aim to find the underlying cause of hypernatremia.
• Fluid Replacement: Correct the fluid deficit before proceeding with elective surgery.

Emergency Surgeries

• Frequent Sodium Measurements: Monitor sodium levels frequently during the procedure.
• Invasive Blood Pressure Monitoring: Necessary due to the likelihood of hypovolemia.
• Adjusted Medication Doses: Reduced volume of distribution requires reduced doses of IV induction agents.

Hyponatremia

Summary

Anaesthesia Considerations

• Manifestation of Serious Underlying Disorder: Hyponatremia can indicate a significant underlying health issue.
• Safe Plasma Concentration: Plasma sodium concentration > 130 mEq/L is considered safe for anaesthesia (Oxford Handbook suggests > 120 mEq/L).
• Cerebral Oedema: May manifest as low minimum alveolar concentration (MAC) requirements intraoperatively and present as confusion, agitation, or somnolence postoperatively.
• ECG Changes: Bradycardia, QRS widening, T wave inversions, ST segment changes, ventricular fibrillation (VF), or ventricular tachycardia (VT).

Acute vs. Chronic Hyponatremia

• Risk of Central Pontine Myelinolysis: Rapid overcorrection can lead to this serious condition.

Physiologic Manifestations (Severe = Neurologic Symptoms or < 120 mEq/L)

• Central Nervous System: Decreased level of consciousness (LOC), seizures, cerebral edema, central pontine myelinolysis.
• Volume Status: Can present with hyperor hypovolemia.
• Respiratory Arrest: Risk increases with severe hyponatremia.
• Decreased MAC: Lower anaesthetic requirements due to CNS effects.

Aetiology

Hypervolemia

• Conditions: Congestive cardiac failure (CCF), hypoalbuminemia (cirrhosis, nephrotic syndrome), renal failure, transurethral resection of the prostate (TURP) syndrome.

Euvolemia

• Conditions: Syndrome of inappropriate antidiuretic hormone (SIADH) due to stress, pain, post-neurosurgery; psychogenic causes.

Hypovolemia

• Conditions: Cerebral salt wasting, hemorrhage, Addison’s disease, peritonitis, edema from burns, diarrhea, diuretics.

Management

• Preoperative Correction: Correct severe hyponatremia before surgery.
• Volume Deficit: Restore volume deficit with normal saline.
• Normal Saline: 20 mL/kg IV bolus as needed.
• Plasma Sodium Restoration: Calculate sodium deficit and replace accordingly.

Sodium Deficit Calculation

• Formula:
  Na deficit (mEq) = TBW X (Desired Na} – (Present Na)

• Replacement with NaCl 0.9%:

• NaCl 0.9% = 154{ mEq of Na/L}

• Na deficit/154 = Replacement volume of NaCl (L)

• Avoid Rapid Overcorrection: Target 0.5-1 mEq/hr, with a maximum increase of < 8 mEq in 24 hours. Replace over 48 hours.

• Replacement Rate:
  Replacement volume (mL)/48 hours {mL/h}

Acute Hyponatremia

• Water Restriction: Generally restrict free water intake to 500 mL-1 L/day with or without diuretics.
• Severe Hyponatremia:
  • Hypertonic saline 3% at 1-2 mL/kg/hr until Na > 125 mEq/L.
  • Loop diuretics.
  • Sodium bicarbonate (1 mEq/mL) for seizure control: 0.5-1 mL/kg boluses as needed.

SIADH

• Treatment: Address the underlying cause and implement fluid restriction. Identify and treat any mineralocorticoid deficiency.

ECG Changes

Potassium

Hyperkalaemia

Summary

Calculation for Replacement

• Potassium Deficit Calculation:
• Kdeficit(mmol)= (Knormal lower limit[3.5]−Kmeasured)×body weight (kg)×0.4

Aetiology

Shift

• Causes: Metabolic or respiratory acidosis, diabetic ketoacidosis, digoxin toxicity.

Total Body Excess

• Conditions: Rhabdomyolysis (malignant hyperthermia, crush injuries, burns), post cardiopulmonary bypass, iatrogenic (IV or oral potassium administration), hemolysis, tumor lysis, transfusion (massive transfusion, old packed red blood cells), renal failure, hypoaldosteronism, Addison’s disease.

Drugs

• Medications: Succinylcholine, ACE inhibitors, beta blockers, spironolactone, NSAIDs, cyclosporin.

Systemic Effects

• Cardiovascular: Arrhythmias.
• Muscular: Muscle weakness.

ECG Changes in Hyperkalemia

• Mild (5.5-6.5 mEq/L): Peaked T waves, prolonged PR interval (1st degree AV block).
• Moderate (6.5-8.0 mEq/L): Loss of P wave, prolonged QRS, ST segment elevation, ectopic beats/escape rhythms.
• Severe (>8.0 mEq/L): Progressive widening of QRS, bundle branch blocks, fascicular blocks, sine wave pattern, ventricular fibrillation, asystole.

Membrane Potential and Conduction

• Resting Membrane Potential: Less negative according to Nernst equation due to lower intracellular to extracellular potassium gradient, resulting in reduced potassium efflux.
• Threshold Potential: Reduced gap between resting membrane potential and threshold potential increases irritability.
• Phase 4 Slope: Lower slope reduces automaticity, leading to slower conduction.

Management

• Acute Management: Immediate measures to stabilize cardiac membranes (e.g., calcium gluconate) and shift potassium intracellularly (e.g., insulin with glucose, beta-agonists).
• Chronic Management: Address underlying causes and adjust medications affecting potassium levels. Maintain careful monitoring and correction of serum potassium levels to avoid complications.

Drug Interactions

• Succinylcholine: Contraindicated.
• Non-Depolarizing Muscle Relaxants: Resistance may occur.

Management

Stabilize Myocardium

• Calcium Gluconate: 100 mg/kg IV to stabilize cardiac membranes.

Shift Potassium Intracellularly

• Insulin and Glucose: Administer 0.1 units/kg of insulin with 0.5-1 g/kg of glucose (approximately 25 g of glucose for every 10 units of insulin).
• Sodium Bicarbonate: 1 mEq/kg IV to correct acidosis.
• Ventolin (Albuterol): 5-10 mg via nebulizer or 5 mcg/kg IV to stimulate cellular potassium uptake.
• Hyperventilation: To induce respiratory alkalosis, which helps shift potassium into cells.
• Epinephrine: Can be used to shift potassium intracellularly.

Eliminate Potassium

• Furosemide: 20-40 mg IV to promote renal excretion of potassium.
• Kayexalate: 30 g per rectum (PR) or orally (PO) to bind potassium in the gastrointestinal tract.
• Dialysis: For severe hyperkalemia or in cases of renal failure where other methods are insufficient.

Hypokalemia

Summary

Anaesthesia Considerations for Hypokalemia

Intraoperative Monitoring and Management

• ECG Monitoring: Continuous ECG monitoring intraoperatively is essential. Replace potassium if arrhythmias develop.
• Avoid Worsening Hypokalemia:
  • Avoid administering insulin, glucose, beta agonists, bicarbonate, hyperventilation, and diuretics as they can exacerbate hypokalemia.
• Sensitivity to Non-Depolarizing Muscle Relaxants (NDMRs): Increased sensitivity necessitates a reduced dose and the use of Train-of-Four (TO4) monitoring.

ECG Changes in Hypokalemia

• T Wave Changes: Progressive flattening of the T wave.
• U Wave: Increasingly prominent U wave.
• P Wave: Increased amplitude.
• P–R Interval: Prolongation.
• ST Segment: Depression.

Membrane Potential and Conduction

• Resting Membrane Potential: More negative according to the Nernst equation.
  • Lower serum potassium (K⁺) increases the chemical gradient, leading to more potassium moving extracellularly.
• Threshold Potential: Larger gap between resting membrane potential and threshold potential decreases cellular irritability.
• Phase 4 Slope: Steeper gradient increases automaticity, making the heart more prone to arrhythmias.

Summary of Steps for Management

1. Monitor ECG: Continuously during the procedure.
2. Replace Potassium: If arrhythmias develop, administer potassium cautiously.
3. Avoid Exacerbating Hypokalemia:
   • Do not administer treatments that lower serum potassium (insulin, glucose, beta agonists, bicarbonate, hyperventilation, diuretics).
4. Adjust NDMR Dosage: Reduce the dose of non-depolarizing muscle relaxants and utilize TO4 monitoring to guide dosing.

Calcium

Summary

Calcium: Physiological Role and Regulation

Overview

• Highly Regulated Cation: Calcium (Ca²⁺) is crucial for various physiological processes.
• Functions:
  • Cell Death: Key regulator.
  • Cardiac Muscle: Influences the duration and strength of contraction.
  • Smooth Muscle Contraction: Involved in blood vessels, airways, and uterus.
  • Coagulation: Essential for the blood clotting process.
  • Bone Metabolism: Integral component of bone structure and health.
  • Neurotransmitter and Hormone Release: Facilitates the release of these signaling molecules.

Calcium States in Extracellular Plasma

1. Free Ionized State: Active form.
2. Bound State: Mostly attached to albumin, with some bound to beta-globulins, phosphate, and citrate.

pH Relationship

• Inverse Relationship with pH: An increase in pH leads to a decrease in ionized Ca²⁺ concentration.

Calcium Levels in Plasma

• Total Calcium (Ca²⁺)
  • Normal Range: 2.2-2.5 mmol/L.
  • Distribution: 55% bound, 45% ionized.
• Ionized Calcium (Ca²⁺)
  • Normal Range: 1.1-1.3 mmol/L.
  • Represents 50% of total calcium.
• Protein Bound Calcium (Ca²⁺)
  • Normal Range: 0.95-1.2 mmol/L.
  • Accounts for 40% of total calcium.
• Complexed Calcium (Ca²⁺)
  • Calcium Phosphate and Salts: 0.05 mmol/L.
  • Constitutes 10% of total calcium.

CALCIUM METABOLISM

Vitamin D

• group of related sterols
  cholecalciferol is formed in the skin
  -> in liver to 25-hyrdroxcholecalciferol
  -> in kidney proximal tubules to 1,25-dihydroxycholecalciferol
  -> this then helps calcium absorption in the intestine
• controlled by parathyroid hormone
  -> increases intestinal absorption of Ca2+
  -> increases renal Ca2+ reabsorption
  -> mobilises bone Ca2+ & PO43-

Parathyroid Hormone

• secretion increased by hypocalaemia and hypomagnesaemia
• secretion decreased by hypercalcaemia and hypermagnesaemia
  -> mobilses Ca2+ from bone
  -> increases renal Ca2+ reabsorption
  -> increases renal PO43excretion
  -> increases formation of 1, 25-dihyroxycholecalciferol

Calcitonin

• antagonist of parathyroid hormone
• secreted by the parafollicular cells of the thyroid gland in response to:
  –hypercalcaemia
  –catecholamines
  –gastrin
  -> inhibits the mobilisation of bone Ca2+
  -> increases renal Ca2+ & PO43excretion

Hypercalcemia

Summary

Hypercalcemia Management

1. 0.9% Normal Saline (NS)

   • Mechanism: Replaces volume and sodium (Na⁺), which will be co-excreted with calcium (Ca²⁺).
   • Indication: Initial treatment to address dehydration and promote renal calcium excretion.

2. Calcitonin

   • Mechanism: Reduces bone resorption and has a mild calciuric effect.
   • Indication: Used in severe hypercalcemia.
   • Onset: Rapid.

3. Bisphosphonates

   • Mechanism: Decrease osteoclast-mediated bone resorption.
   • Indication: Effective in reducing calcium levels by inhibiting bone breakdown.

4. Glucocorticoids

   • Mechanism: Useful in cases where hypercalcemia is caused by endogenous calcitriol overproduction.
   • Indication: Only used if there is increased calcium due to endogenous calcitriol overproduction.

5. Diuretics

   • Consideration: Generally avoided unless the patient is fluid overloaded.
   • Rationale: Diuretics can worsen dehydration and are typically not recommended in the initial management of hypercalcemia unless managing fluid overload.

ECG Changes

Correction of Calcium

Importance of Correcting Calcium

The correction formula ensures that hypoalbuminemia is not masking hypercalcemia. Without access to ionized calcium measurements (though often available in ICU and theatre via ABG), a low total calcium might falsely indicate low ionized calcium. Albumin affects total calcium but not ionized calcium.

Mechanism

Calcium in serum is bound to proteins, primarily albumin. Therefore, total serum calcium concentration in patients with low or high serum albumin levels may not reflect the physiologically significant ionized (free) calcium concentration.

Correction Formula

For every 1 g/dL (10 g/L) reduction in serum albumin concentration, the total calcium concentration is lowered by approximately 0.8 mg/dL (0.02 mmol/L) without affecting the ionized calcium concentration. This does not produce symptoms or signs of hypocalcemia.

Key Points

• Purpose: To determine if low albumin is hiding hypercalcemia.
• Application: Applies only to total calcium, not ionized calcium.
• pH Effect: pH affects ionized calcium—low pH causes H+ to displace Ca from albumin, increasing ionized calcium.

Conversion

• 0.8 mg/dL is equivalent to 0.02 mmol/L.

Hypocalcemia

Summary

Causes of Hypocalcemia

Intake Reduced

• Calcium (Ca²⁺)
• Vitamin D
• Phenytoin: Increases metabolism of vitamin D

Redistribution

• Alkalosis
• Citrate toxicity
• Hyperphosphatemia
• Pancreatitis
• Tumor lysis syndrome
• Rhabdomyolysis
• Decreased bone turnover
• Hypoparathyroidism
• Drugs: Bisphosphonates, proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), gentamicin

Output Increased

• Urinary: Ethylene glycol, cisplatin, protamine, loop diuretics
• Non-urinary: Bleeding, plasmapheresis, citrate renal replacement therapy (RRT)

Causes of Hypocalcemia and Acid-Base Disturbance

• Metabolic Alkalosis: Citrate toxicity
• Metabolic Acidosis: Acute renal failure, tumor lysis syndrome, rhabdomyolysis, pancreatitis, ethylene glycol poisoning, hydrofluoric acid exposure, sepsis, burns

Clinical Presentation of Hypocalcemia

Symptoms

• Perioral numbness
• Paresthesias
• Muscle cramps
• Mild mental status changes (e.g., irritability)
• Seizures
• Tetany
• Collapse
• Laryngospasm
• To identify the cause: consider diet, drugs, and symptoms specific to the cause

Signs

• Chvostek Sign: Tapping facial nerve anterior to ear causes spasm of facial muscles
• Trousseau Sign: Inflating BP cuff traps the median nerve, leading to carpal spasm
• Hypotension
• Arrhythmias (prolonged QT interval)
• Heart failure
• Signs specific to the underlying cause

Management of Hypocalcemia

• Treat the underlying cause
• Severity-proportional treatment
  • Oral Calcium
  • Magnesium Replacement
  • Vitamin D Supplementation
  • Intravenous Calcium
    • 10 mL calcium gluconate = 2.3 mmol = 93 mg calcium
    • 10 mL calcium chloride = 6.8 mmol = 272 mg calcium

Indications for IV Calcium Therapy

• Symptomatic hypocalcemia
• Ionized calcium (Ca²⁺) <0.8 mmol/L
• Hyperkalemia
• Calcium channel blocker overdose
• Hypermagnesemia
• Hypocalcemia with high inotrope requirement
• Massive transfusion
• Post-cardiopulmonary bypass

Magnesium

• Only ionized magnesium (60% of total plasma Magnesium) is physiologically active, although it is not measured routinely
• Low serum albumin lowers total plasma Mg but ionized Mg may be normal

Hypomagnesaemia

Summary

Definition

• Serum magnesium < 0.75 mmol/L
• Associated with increased ICU mortality
• Common, affecting 10-65% of ICU patients

Causes

Decreased Intake

• Protein-calorie malnutrition
• Enteral nutrition
• Alcoholism
• Total parenteral nutrition (TPN)
• Malabsorption (e.g., gastric-bypass surgery, chronic pancreatitis, sprue, steatorrhea, congenital malabsorption, inflammatory bowel disease)
• Proton pump inhibitors (mechanism unclear, likely decreased GI absorption)

Increased Loss

• Gastrointestinal:
  • Nasogastric drainage
  • Diarrhea
  • Vomiting
• Increased Renal Tubular Flow:
  • Volume expansion
  • Osmotic diuresis (hyperglycemia, mannitol)
  • Diuretics (loop/thiazide/osmotic)
  • Antimicrobials (aminoglycosides, amphotericin B, carbapenems, pentamidine)
  • Chemotherapy (cisplatin)
• Renal Tubular Dysfunction:
  • Renal tubular acidosis
  • Acute tubular necrosis
  • Urinary tract obstruction
  • Transplantation
• Other:
  • Hypercalcemia
  • Hyperaldosteronism
  • Congenital renal magnesium wasting (Gitelman syndrome, Bartter syndrome)

Pathophysiology

• Effects on Membrane Potentials:
  • Magnesium deficiency causes a drop in intracellular potassium and a rise in intracellular sodium
  • Elevation in resting potential leads to increased inward calcium current, enhancing neurological and cardiac irritability
• Potassium Reabsorption:
  • Magnesium is essential for renal potassium reabsorption
  • Deficiency increases activity of renal ATP-dependent ROMK channels (especially in thick ascending loop of Henle and cortical collecting ducts), leading to increased potassium excretion
• Hypocalcemia:
  • Due to impaired release of parathyroid hormone (PTH) and its peripheral action

Clinical Presentation

Symptoms (usually at Levels <0.5 mmol/L)

• CNS:
  • Neuromuscular irritability
  • Trousseau and Chvostek signs (even with normal ionized calcium)
  • Weakness/fatigue (“lemonade legs”)
  • Vertical nystagmus
  • Tetany
  • Seizures
  • Reversible blindness
• Cardiovascular:
  • Arrhythmia, especially torsades de points (resistant to cardioversion)
  • ECG changes similar to hypokalemia
  • Digitalis toxicity
• Metabolic:
  • Resistant hypocalcemia
  • Resistant hypokalemia
  • PTH resistance and impaired PTH release

Management

• Resuscitation:
  • Treat dysrhythmias, seizures, and other life-threatening conditions
• Magnesium Replacement:
  • Intravenous magnesium replacement preferred in malabsorption states and acute symptomatic states
  • Oral magnesium replacement (120 mg TDS)
• Correction of Co-existing Electrolyte Abnormalities:
  • Address hypokalemia and hypocalcemia
• Potassium-Sparing Diuretics:
  • For chronic renal magnesium wasting
• Seek and Treat Underlying Cause

Electrolyte Abnormalities Associated with Hypomagnesemia

• Hypokalemia (40%)
• Hypophosphatemia (30%)
• Hyponatremia (27%)
• Hypocalcemia (22%)

ECG Changes with Hypomagnesemia

• Prolonged QTc
• Torsades de points

Hypermagnesemia

Summary

Definition

• Normal Serum Magnesium Range: 1.3-2.2 mEq/L
• Toxic Level: >4 mEq/L
• Incidence: Rare, usually iatrogenic
• Note: Elevated magnesium (hypermagnesemia) is closely associated with elevated potassium (hyperkalemia) and decreased calcium (hypocalcemia)

Causes

1. Iatrogenic

   • Hyperalimentation
   • Intravenous and oral magnesium
   • Laxatives, enemas, antacids (especially in elderly and those with renal failure)

2. Renal Failure

3. Other

   • Perforated viscus with continued oral intake
   • Tumor lysis syndrome (increased potassium, magnesium, phosphate, and decreased calcium)
   • Rhabdomyolysis

Clinical Presentation

• Often asymptomatic
• Serum Magnesium >4 mEq/L:
  • Muscle weakness
  • Hyporeflexia
  • Nausea and vomiting
  • Hypotension secondary to vasodilation
• Serum Magnesium >10 mEq/L:
  • Coma
  • Hypoventilation
  • Neuromuscular paralysis
  • Cardiac arrhythmias, bradycardia, and death

Complications

• ECG Changes (similar to hyperkalemia):
  • Increased PR interval and QTc
  • Prolonged QRS complex
  • Peaked T waves and flattened P waves
  • Complete atrioventricular (AV) block and asystole

Management

• Discontinue Magnesium Intake
• Antagonize Magnesium Effects:
  • Calcium Chloride: 10% solution in 5-10 mL, repeat as necessary to treat life-threatening arrhythmias
• Remove Magnesium from Serum:
  1. Dialysis: Treatment of choice
  2. Forced Diuresis:
     • Intravenous normal saline and furosemide
     • Monitor for hypocalcemia, which can exacerbate symptoms

Phosphate

Functions of Phosphate (PO4)

• Component of ATP
• Constituent of nucleic acids
• Integral part of phospholipids
• Enzymatic co-factors
• Involvement in cyclic GMP (cGMP) and cyclic AMP (cAMP)
• Part of 2,3-diphosphoglycerate (2,3-DPG)
• Essential for enzymes in the glycolytic pathway
• Acts as a buffer in the maintenance of plasma pH
• Important for immune system integrity
• Involved in the coagulation cascade

Hypophosphatemia

Definition

• Hypophosphatemia: Serum phosphate < 0.8 mmol/L
  • Mild: 0.65-0.8 mmol/L
  • Moderate: 0.32-0.65 mmol/L
  • Severe: Actions on intestine, kidneys, and bone

Pathophysiology

• Parathyroid hormone (PTH) increases phosphate and calcium release from bone but increases excretion in the kidney by inhibiting reabsorption in the proximal tubule.
• Vitamin D from the kidneys increases absorption of calcium and phosphate in the jejunum.

Causes

• Decreased Intake:
  • Malnutrition
  • Phosphate binders
  • Vitamin D deficiency
  • Malabsorption
  • Total parenteral nutrition (TPN)
• Redistribution:
  • Refeeding syndrome
  • Insulin administration in diabetic ketoacidosis (DKA)
• Increased Output:
  • Urinary: Diuretics, osmotic diuresis, hyperparathyroidism, proximal tubular dysfunction (Fanconi’s syndrome)
  • Non-urinary:
    • Upper GI
    • Mid GI
    • Lower GI (diarrhea)
    • Other: Sweat, burns, sepsis, bleeding

Clinical Features

• Cardiovascular:
  • Reversible dilated cardiomyopathy
  • Increased inotrope requirement
• Respiratory:
  • Respiratory failure
  • Ventilator dependence
  • Left shift of the oxygen-hemoglobin dissociation curve
• Neurological:
  • Altered mental state
  • Weakness
  • Gait disturbance
  • Paresthesias
• Hematological:
  • Hemolysis
  • Disorders of white blood cell function
• Endocrine:
  • Bone demineralization
• Musculoskeletal:
  • Rhabdomyolysis

Management

• Ensure adequate feeding (caution in refeeding syndrome)
• Oral Phosphate: For levels 0.65-0.89 mmol/L
• Intravenous Phosphate:
  • KH2PO4: 10 mmol of phosphate and 10 mmol of potassium in 10 mL
  • NaKH2PO4: 13.4 mmol of phosphate, 21.4 mmol of sodium, 2.6 mmol of potassium in 20 mL
  • Administer 1 ampoule over 1 hour
• Caution with phosphate administration in renal failure
• Monitor for hyperphosphatemia, hypocalcemia, hypotension, tetany, and ECG changes

Hyperphosphatemia

Definition

• Hyperphosphatemia: Elevated serum phosphate levels

Causes

• Renal Failure
• Increased Renal Resorption:
  • Hypoparathyroidism
  • Thyrotoxicosis
• Cellular Injury with Release:
  • Tumor lysis syndrome
  • Rhabdomyolysis
  • Hemolysis
  • Ischemic gut
• Medication-Related:
  • Phosphate-containing laxatives
  • Excessive phosphate administration
  • Bisphosphonate therapy

Clinical Features

• Symptoms often related to associated hypocalcemia:
  • Precipitation of calcium (nephrolithiasis)
  • Interference with parathyroid hormone-mediated bone resorption
  • Decreased vitamin D levels
  • Muscle cramping
  • Tetany
  • Hyperreflexia
  • Seizures
  • Cardiovascular manifestations (prolonged QT interval)

Management

• Treat underlying condition
• Limit phosphate intake
• Enhance urinary phosphate excretion (saline, acetazolamide)
• Dialysis
• Oral phosphate binders (calcium and aluminum salts)

Links

• Endocrine and Metabolic
• Acid base

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References:

1. The Calgary Guide to Understanding Disease. (2024). Retrieved June 5, 2024, from https://calgaryguide.ucalgary.ca/
2. Eaddy, N. and Watene, C. (2023). Perioperative management of fluids and electrolytes in children. BJA Education, 23(7), 273-278. https://doi.org/10.1016/j.bjae.2023.03.006
3. FRCA Mind Maps. (2024). Retrieved June 5, 2024, from https://www.frcamindmaps.org/
4. Anesthesia Considerations. (2024). Retrieved June 5, 2024, from https://www.anesthesiaconsiderations.com/
5. ICU One Pager. (2024). Retrieved June 5, 2024, from https://onepagericu.com/
6. Sahir S Rassam, David J Counsell, Perioperative electrolyte and fluid balance, Continuing Education in Anaesthesia Critical Care & Pain, Volume 5, Issue 5, October 2005, Pages 157–160, link

Summaries:
Endocrine physiology

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© 2022 Francois Uys. All Rights Reserved.