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Hypernatremia

Definition

• Moderate hypernatremia: 146-159 mEq/L (fairly well tolerated)
• Severe hypernatremia: > 160 mEq/L (associated with significant morbidity/mortality)
• Hospital-acquired hypernatremia with Na+ > 150 mEq/L carries a severity-adjusted relative risk of death of 2.6

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Pathophysiology

• Thirst stimulus (most powerful defense)
• ADH (vasopressin) release - concentrates urine
• Brain generates idiogenic osmoles (organic osmolytes) within hours to pull water back in - this is why rapid correction causes cerebral edema

• Inhibits insulin release and increases insulin resistance → hyperglycemia
• Decreases hepatic gluconeogenesis and lactate clearance
• Impairs cardiac function

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Classification and Causes

1. Hypovolemic Hypernatremia (water loss > sodium loss)

• Diuretics (loop > thiazide)
• Osmotic diuresis (glucose, mannitol, enteral feeds)
• Post-obstructive diuresis

• GI losses: diarrhea, protracted vomiting, continuous GI suction
• Skin losses: burns, excessive sweating, heatstroke
• Increased insensible losses

2. Euvolemic Hypernatremia (pure water deficit, normal sodium stores)

• Diabetes Insipidus (DI) - most important cause
  • Central DI: insufficient vasopressin secretion (head trauma, neurosurgery, sarcoidosis, malignancy, autoimmune, idiopathic)
  • Nephrogenic DI: vasopressin resistance (lithium, hypercalcemia, hypokalemia, chronic renal insufficiency, sickle cell disease, polycystic kidney disease)
• Low free water intake (elderly, delirium, intubation, dementia)
• Intracellular water shift (intensive exercise, seizures from ECT)
• Hypothalamic dysfunction / reset osmostat

3. Hypervolemic Hypernatremia (gain of hypertonic fluid)

• Salt tablet or seawater ingestion
• Hypertonic saline infusions / hypertonic sodium bicarbonate
• Hypertonic saline enemas
• Poorly diluted enteral feeds
• Primary hyperaldosteronism (Conn's syndrome) - concurrent hypertension + hypokalemia
• Cushing's syndrome
• Hemodialysis with incorrect dialysate

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At-Risk Populations

• Elderly (impaired thirst sensation, "reset osmostat")
• Infants
• Patients with altered mental status / delirium
• Intubated / paralyzed patients
• Patients with dementia

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Clinical Features

Symptoms (severity correlates with rate of onset, not just absolute level)

• Mild: Thirst, restlessness, irritability, muscle weakness
• Moderate: Lethargy, insomnia, confusion
• Severe: Depressed sensorium, stupor, coma, seizures, focal neurological deficits
• Rapid-onset hypernatremia is more dangerous than chronic (less time for idiogenic osmole compensation)

Signs

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Diagnostic Workup

• Serum electrolytes, BUN, creatinine, glucose
• Serum osmolality
• Urine sodium + urine osmolality

• Urine osmolality > 600 mOsm/kg → kidneys concentrating maximally → impaired water intake is the cause → look for precipitating factor
• Urine osmolality < 600 mOsm/kg → impaired water intake + impaired renal water conservation → administer ADH (desmopressin):
  • Urine osmolality increases > 50% → Central DI
  • Minimal response → Nephrogenic DI (consider lithium, hypercalcemia)

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Free Water Deficit Calculation

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Management

Three Goals (in order):

1. Correct hemodynamic instability first - isotonic normal saline (0.9% NaCl) until hemodynamically stable. Do not chase the sodium until volume is restored - homeostatic Na+ retention mechanisms will prevent progress.
2. Treat the underlying cause - fever, vomiting, DI, etc.
3. Replace free water deficit slowly

Rate of Correction

• Acute hypernatremia (developed over hours, e.g., salt loading): rapid correction at ≥ 1 mEq/L/hr is relatively safe
• Chronic hypernatremia (developed over days-weeks, the usual case): correct at no more than 0.5 mEq/L/hr or 10-12 mEq/day - brain has generated idiogenic osmoles; rapid correction causes cerebral edema

Failure to consider ongoing sensible and insensible losses is the most common cause of undercorrection.

Fluid Choice

Diabetes Insipidus - Specific Treatment

• Central DI: Desmopressin (DDAVP) 1-2 µg IV/SC in the acute setting - effective for both polyuria and hypernatremia
• Nephrogenic DI: Remove causative drug (lithium), treat hypercalcemia/hypokalemia; low-sodium diet + thiazide diuretics (paradoxically reduce urine output)

Monitoring

• Recheck serum Na+ every 4-6 hours during active correction
• Patients whose hypernatremia is corrected within 72 hours have lower mortality than those corrected beyond 72 hours
• Fewer than 50% of hospital-acquired hypernatremia patients receive free water replacement within 24 hours of identification - this is a recognized gap in care

Disposition

• Most require hospitalization (dehydration + underlying comorbidities)
• Mild cases with intact thirst and no underlying cause may be managed with increased oral water at home

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Key Points Summary

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Haemorrhage, Haemostasis, Blood Products & Transfusion - A Surgical Overview

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PART 1: MECHANISM OF HAEMOSTASIS

Step 1 - Arteriolar Vasoconstriction

Step 2 - Primary Haemostasis (Platelet Plug Formation)

1. Vascular injury exposes subendothelial collagen and von Willebrand Factor (vWF)
2. Platelets adhere via GpIb receptors binding to vWF
3. Adhesion triggers platelet activation - shape change from discs to spiky plates, release of granule contents (ADP, thromboxane A2)
4. ADP and TXA2 recruit additional platelets
5. Fibrinogen bridges platelets via GpIIb-IIIa receptors → platelet aggregation
6. Result: the primary haemostatic plug (fast but fragile)

Step 3 - Secondary Haemostasis (Coagulation Cascade)

Step 4 - Clot Stabilisation and Counter-Regulation

• Factor XIII (activated by thrombin) covalently crosslinks fibrin strands
• Platelet contraction compacts and strengthens the clot
• Excessive clotting is limited by:
  • Washout and hepatic clearance of activated factors
  • Requirement for phospholipid surfaces (only on activated platelets)
  • Endothelial anticoagulants: thrombomodulin, protein C, TFPI
  • Fibrinolysis via tissue plasminogen activator (tPA) → plasmin → fibrin degradation

Key summary: Primary haemostasis = platelet plug (GpIb-vWF adhesion + GpIIb-IIIa aggregation). Secondary haemostasis = fibrin mesh (TF-VII → cascade → thrombin → fibrin). Factor XIII stabilises.

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PART 2: HAEMORRHAGE - TYPES AND CLASSIFICATION

A. Classification by Vessel Type

B. Classification by Timing (Surgical)

C. Classification by Cause

• Traumatic - direct injury
• Operative/Iatrogenic - surgical bleeding
• Spontaneous - coagulopathy, aneurysm rupture, erosion by tumour or infection

D. Classification by Location

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PART 3: ATLS HAEMORRHAGIC SHOCK CLASSIFICATION

Important: BP does not theoretically fall until Class III (>30% blood loss = ~2 L, equivalent to a "six-pack of soda"). BP alone is not a reliable early indicator. The Shock Index (SI) = HR/SBP is a better marker; SI > 0.9 is highly suggestive of critical bleeding.

Relative bradycardia (HR < 100 with SBP < 90) paradoxically carries lower mortality - this vagally-mediated response reduces cardiac output and slows exsanguination. Patients with HR 60-90 bpm have the best survival.

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PART 4: MANAGEMENT OF HAEMORRHAGE

Principles: The "Double-Armed" Approach

Step-by-Step Management

• Two large-bore IV lines; send blood for type and crossmatch
• If IV access fails - intraosseous or large-bore central venous access

• Direct pressure / tourniquet for extremity bleeding
• Haemostatic dressings for junctional wounds
• Damage control surgery / angioembolisation for internal bleeding

• Target SBP 70-90 mmHg (or palpable radial pulse) until definitive haemorrhage control
• Controlled resuscitation with 250 mL boluses - reduces mortality vs. aggressive 2 L boluses
• Exception: Traumatic brain injury - maintain adequate cerebral perfusion pressure (higher targets)

• Class I-II: 1 L warmed isotonic crystalloid and observe response
  • Sustained response = bleeding stopped
  • Transient/no response = ongoing haemorrhage, switch to blood products
• Class III-IV: direct to blood products and massive transfusion protocol

• Type-specific, non-crossmatched blood can be used in emergencies
• Type O-negative for pregnant females and females of childbearing age
• Type O-positive acceptable in males/post-menopausal females when O-neg unavailable

Damage Control Resuscitation Box (ATLS Principles)

1. Direct pressure / tourniquet / haemostatic packing
2. Early transfer to OR or angiography suite
3. Minimise crystalloid (max 1 L before blood)
4. Balanced blood products 1:1:1
5. TXA within 3 hours
6. Permissive hypotension (SBP 70-90) until haemorrhage control
7. Treat hypothermia, acidosis, and coagulopathy - the "lethal triad"

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PART 5: BLOOD PRODUCTS AND THEIR INDICATIONS

1. Whole Blood

• Rarely available in civilian practice
• Significant advantage: coagulation factor-rich, metabolically active if fresh
• Military studies show improved mortality and decreased component use
• Some level I trauma centres reintroducing in trauma resuscitation

2. Packed Red Blood Cells (PRBCs)

• ~330 mL/unit; haematocrit 50-70%
• Stored in SAG-M (saline-adenine-glucose-mannitol) at 2-6°C; shelf life 5 weeks
• Indications:
  • Acute blood loss to replace circulating volume
  • Perioperative anaemia to ensure oxygen delivery
  • Symptomatic chronic anaemia

Historical target of Hb > 10 g/dL is now shown to increase morbidity and mortality vs. lower targets.

3. Fresh Frozen Plasma (FFP)

• Removed from fresh blood; stored at -40 to -50°C; shelf life 2 years
• Contains all coagulation factors
• Indications:
  • Coagulopathic haemorrhage (first-line)
  • Massive transfusion (as part of 1:1:1 ratio)
  • Reversal of warfarin in urgent bleeding
  • DIC with active bleeding
• Note: Rh-D negative women receiving Rh-D positive FFP should receive Rh-D immunoglobulin (small risk of sensitisation from red cell fragments)

4. Cryoprecipitate

• Cold-precipitated supernatant of FFP; stored at -30°C; shelf life 2 years
• Rich in: Fibrinogen, Factor VIII, Factor XIII, vWF
• Indications:
  • Hypofibrinogenaemia (most common surgical indication)
  • Factor VIII deficiency (haemophilia A, when FVIII concentrate unavailable)
  • vWD Type 1-2
  • DIC with low fibrinogen
• Often guided by thromboelastometry (TEG/ROTEM)

5. Platelets

• Pooled concentrate (~250 × 10⁹/L); stored at 20-24°C with agitation; shelf life only 5 days
• Indications:
  • Thrombocytopenia with active bleeding or pre-surgery
  • Platelet dysfunction (e.g., clopidogrel, aspirin) with active surgical bleeding
• Patients on clopidogrel may need near-continuous platelet infusion during major surgery
• DDAVP (desmopressin) can also improve platelet function in some settings

6. Prothrombin Complex Concentrates (PCCs)

• Highly purified pooled plasma concentrates
• Contain Factors II, IX, X (3-factor PCC) or also Factor VII (4-factor PCC)
• Indications:
  • Urgent reversal of vitamin K antagonists (warfarin)
  • Massive haemorrhage when FFP unavailable or time-critical
  • Haemophilia B (Factor IX deficiency)

7. Tranexamic Acid (TXA)

• Anti-fibrinolytic agent (lysine analogue - inhibits plasminogen activation)
• Surgical indication: Most bleeding trauma patients are hyperfibrinolytic; TXA should be given empirically as early as possible, within 3 hours of injury
• CRASH-2 trial: significant reduction in death from haemorrhage
• Also used in elective surgery to reduce perioperative blood loss

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PART 6: MASSIVE TRANSFUSION

Massive Transfusion Protocol (MTP) Ratio

• 1:1:1 - PRBCs : FFP : Platelets (one apheresis unit or "six-pack")
• Supported by the PROPPR randomised trial (Holcomb et al.)
• 1:1:1 vs 1:1:2 showed no mortality difference at 24h/30d but better haemostatic laboratory profile with 1:1:1
• Higher plasma/platelet ratios in early resuscitation associated with decreased mortality (PROMMTT study)

Complications of Massive Transfusion

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PART 7: TRANSFUSION REACTIONS AND COMPLICATIONS

Immediate Reactions

Delayed Reactions

Infectious Complications

In the UK, all donations are leukodepleted (reduces immunogenicity and vCJD risk). All units tested for HIV-1/2, Hep B, Hep C, syphilis. ABO and Rh-D typed with screen for irregular antibodies.

1. Stop the transfusion
2. Notify the blood bank
3. Retype and crossmatch a new sample - so transfusion can resume safely as quickly as possible

Do not abandon all future transfusion after a reaction - reactions are usually unit-specific and patient-specific. Appropriately matched future units can be transfused safely.

Premedication

• Routine premedication (paracetamol/diphenhydramine) is NOT recommended for all patients
• Reserved for patients with prior febrile or allergic transfusion reactions

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PART 8: BLOOD GROUPS AND COMPATIBILITY

ABO System

• O-negative: universal donor (no A, B, or Rh-D antigens)
• AB: universal recipient
• Rhesus D system: major cause of haemolytic transfusion reactions and haemolytic disease of the newborn

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Summary Framework

HAEMORRHAGE
├── By vessel: Arterial / Venous / Capillary
├── By timing: Primary / Reactionary / Secondary
├── By severity (ATLS Class I-IV based on % blood volume lost)
│
HAEMOSTASIS
├── Step 1: Vasoconstriction (endothelin)
├── Step 2: Primary platelet plug (vWF-GpIb → GpIIb-IIIa-fibrinogen)
├── Step 3: Coagulation cascade (TF-VII → thrombin → fibrin)
└── Step 4: Clot stabilisation (FXIIIa crosslinks fibrin) + fibrinolysis
│
MANAGEMENT (haemorrhagic shock)
├── Control bleeding (pressure/tourniquet/surgery/IR)
├── Permissive hypotension (SBP 70-90 until control)
├── Damage control resuscitation: PRBCs:FFP:Platelets = 1:1:1
├── TXA within 3 hours
└── Treat lethal triad: hypothermia + acidosis + coagulopathy
│
BLOOD PRODUCTS
├── PRBCs: O2 carriage; trigger Hb < 6-8 g/dL
├── FFP: all factors; coagulopathy/massive transfusion
├── Cryoprecipitate: fibrinogen + FVIII + FXIII; hypofibrinogenaemia
├── Platelets: thrombocytopenia/platelet dysfunction; 5-day shelf life
└── PCC: Factor II/IX/X; urgent warfarin reversal
│
TRANSFUSION COMPLICATIONS
├── Haemolytic (ABO) → STOP, hydrate, Coombs
├── FNHTR → paracetamol, rule out haemolytic
├── TRALI → supportive, no diuretics
├── TACO → diuretics, slow rate
└── Infectious: extremely rare with modern screening

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