Y04. Pharmacopeia: Intravenous Fluid Pharmacology

PAST QUESTIONS – I02: Intravenous Fluids (Click to Open)

SYLLABUS (Fourth Edition, 2023)

LEVEL 1	LEVEL 2	LEVEL 3
Electrolytes and Buffers
Magnesium	Calcium chloride
Potassium	Calcium gluconate
Sodium bicarbonate	Phosphate
Crystalloids
0.9% Saline
Glucose containing solutions
Hartmann’s/Plasmalyte
Hypertonic saline solutions
Colloids
Albumin

N.B. The Syllabus tables used in out Pharmacopeia seem incomplete, but that is intentional because we have only included groups/classes/drugs which are mentioned directly in the syllabus or have been asked before in the exams.

TRAINEE EXPECTATIONS

Trainees are expected to understand a drug’s pharmacology in the context of normal physiology, extremes of age (i.e., neonates, paediatrics, and the elderly), obesity, pregnancy (including foetal implications) and critical illness. An understanding of potential toxicity and relevant antidotes is also expected. Agents may be listed in more than one section when they are used for different indications.
This is not an exhaustive list of all drugs relevant to or important in ICU practice. Each drug or classes of drugs have been assigned a details of understanding level outlined below. This is a guide to the minimum level of knowledge expected for that drug.
For classes of drugs where examples are not specified, it is suggested a prototypical drug from the class be studied, as well as the relevant variations within the class exploring the major differences that exist between the agents in that class.

LEVELS OF UNDERSTANDING

Level 1	Level 2	Level 3
For these drugs, a detailed knowledge and comprehension of:	For these drugs a detailed knowledge of:	For these drugs a detailed knowledge of:
Class, Indications, and dose
Mechanism of Action
Pharmacodynamics and Adverse effects
Pharmacokinetics	Important pharmacokinetic differences or considerations when using in ICU
Pharmaceutics

CICMWrecks Tables (Click to Open)

MASTER TABLES	Intravenous Fluids
	Electrolytes and Buffers
INDIVIDUAL TABLES	Sodium bicarbonate
	Magnesium Sulphate
	CSL \| NS
	NS \| 5% Dextrose
	NS \| 4% Albumin
	Mannitol \| Hypertonic NaCl
	Albumin
	4% Albumin

MASTER TABLES

INTRAVENOUS FLUIDS

Pharmacopeia - IV Fluids

	NORMAL SALINE	HYPERTONIC SALINE (3%)	MANNITOL	HARTMANN’s (CSL)	PLASMALYTE	GLUCOSE – 5%	ALBUMIN 4%	ALBUMIN 20%
GROUP	Crystalloid	Crystalloid	Osmotic Diuretic	Crystalloid	Crystalloid	Crystalloid	Colloid	Colloid
CICM Level of Understanding	Level 1	Level 1	Level 3	Level 1	Level 1	Level 1	Level 1	Level 1

INTRODUCTION	intravenous fluid with 9g NaCl in litre of sterile water. Isotonic crystalloid solution	Hypertonic Crystalloid PROS & CONS – See BELOW	an alcohol derived from Dahila tubers (6 carbon sugar) decrease ICP: 0.25g/kg over 15min to 1g/kg PROS & CONS – See BELOW	Compound sodium lactate		intravenous fluid with 50g glucose in litre of sterile water. Hypotonic solution	Natural Colloid	Natural Colloid
USES	1. Initial replacement fluid, in volume depleted or dehydrated patients. Volume depletion may be due to loss of blood, plasma or fluid and electrolytes. 2. Maintenance of hydration during prolonged patient contact time. 3. To keep vein open, as IV route for drugs.	1. Treatment of severe, symptomatic hyponatraemia 2. Management of raised ICP 3. In nebulized form as an expectorant	1. reduce CSF volume -> reduce ICP 2. preserve renal function during perioperative period in jaundice patients under going major vascular surgery. 3. acute management of glaucoma 4. bowel prep 5. initiate diuresis in transplanted kidney 6. treatment for rhabdomyolysis	1. in the treatment of dehydration 2. for the acute expansion of intravascular volume and 3. to provide maintenance fluid and electrolyte requirements in the perioperative period.		1. Maintenance fluid and caloric supply in cases of hypoglycaemia or starvation 2. Fluid replacement along with Insulin in DKA/HHS states 3. Fluid replacement in hypernatremic/ hyperosmolar states	1. Volume replacement 2. Priming of extracorporeal circuits 3. Treatment of hypoalbuminaemic states 4. Replacement fluid during plasma exchange 5. Spontaneous bacterial peritonitis	1. Hypoproteinaemia 2. Shock 3. Burns 4. ARDS 5. Plasma exchange


PHARMACEUTICS (PC)	500 or 1000mls of 0.9% Sodium Chloride solution in a collapsible plastic flask or bag.	3%, 5% and 23.4% Should be administered through CVC due to thrombophlebitis	sterile solution 10-20% in water	As a clear, colourless sterile solution in 500/1000 ml bags		500 or 1000mls of 5% glucose in a collapsible plastic flask or bag	- Heat treated human albumin 500ml bottles containing 10g albumin. - Straw-coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 4% is iso-oncotic	- Heat treated human albumin 200ml bottles containing 200g/L. Straw coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 20% is hyperoncotic with approximately the equivalence of approximately 4x its volume in plasma


PHARMACODYNAMICS (PD)	1. Plasma volume expander 2. Also expands interstitial fluid volume 3. Plasma volume effect is only temporary as most of the saline moves out of the blood vessels quite quickly	MOA: Increased serum sodium concentration. Leads to increase in serum tonicity, leading to diffusion of intracellular fluid into the intravascular space, decreasing cerebral oedema. CNS: Decreased cerebral oedema, decreased ICP, may cause central pontine myelinolysis CVS: Fluid shift into intravascular compartment increases plasma volume and may improve preload ? increase cardiac output ? increase BP	MOA: • increases the osmolarity of the glomerular filtrate -> increasing urinary volume • decreases CSF volume & pressure by (1) decreasing rate of CSF production (2) withdrawing brain extracellular water across the BBB into plasma	CVS The haemodynamic effects of Hartmann’s solution are proportional to the prevailing circulating volume and are short-lived. GU Renal perfusion is temporarily restored towards normal in hypovolaemic patients transfused with the crystalloid. Metabolic/other 1 l of one-sixth molar sodium lactate is potentially equivalent to 290 ml of 5% sodium bicarbonate in its acid-neutralizing effect and to 600 ml of 5% glucose in its antiketogenic effect		Glucose replacement Immediately taken up into ISF and Intracellular spaces	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes and drugs. CVS: Dependent on circulating volume status.	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes, Mg2+ and Ca2+, and acidic drugs. CVS: Dependent on circulating volume status. Raised plasma oncotic pressure may lead to 3x the administered volume being dragged into the plasma within 15min.
PD: Side Effects / Toxicity	1. Fluid overload 2. hyperchloremic metabolic acidosis 3. increased risk of renal failure compared to balanced solutions 4. Injury to endothelial glycocalyx	1. Central pontine myelinolysis 2. Hypernatraemia and hyperosmolarity 3. NAGMA 4. Thrombophlebitis 5. Seizures		The predominant hazard is that of overtransfusion, leading to hypernatraemia, pulmonary oedema, and metabolic alkalosis.		Fluid overload (less than dextrose) Cerebral edema Hyperglycaemia Electrolyte imbalances (hypokalemia,Mg,P) Extravasation/ Vein irritation / tissue necrosis Severe dehydration if given in diabetics without insulin	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI


PHARMACOKINETICS (PK)
PK: Absorption	IV. BA 100%	IV.		IV. BA 100%		IV. BA 100%

PK: Distribution	~15mins: ISF 750mls Plasma volume 250mls. Not distributed to ICF			initially distributed into the plasma but later equilibrates with the extracellular fluid.		ICF 670mls ECF 330mls (with ISF 250mls and plasma 80mls).	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular

PK: Metabolism	Unmetabolized	Unmetabolized	Unmetabolized	- The lactate component is oxidized in the liver to bicarbonate and glycogen over a period of about 2 hours. - This is dependent on cellular oxidative activity, and the mechanism may be depressed by hypoxia and liver dysfunction.		Dextrose is taken into cells and potentially metabolized by multiple pathways, depending on: - Nutritional state - Catabolic or anabolic state - Insulin resistance/DM	Breakdown is predominantly by intracellular lysosome proteases under feedback control	Breakdown is predominantly by intracellular lysosome proteases under feedback control

PK: Excretion	Excreted by kidney Slower than balanced solutions	renally excreted		Excretion Via the urine.		Water is excreted via kidney	Albumin normally has a T1/2 of 19 days	Albumin normally has a T1/2 of 19 days


SPECIAL POINTS	pH 5.0 Osm 308 Tonicity 286 Na 154 Cl 154	Osm 900 Na 450 Cl 450 ADVANTAGES: Cheap • Stable in storage • Easy to transport (small volume) • Very rapid effect (peak @ 10 min, lasts 1 hour) • Seems to have some sort of intrinsic antiinflammatory effect (may decrease MODS) • May also have some rheological benefits At least as potent as mannitol when it comes to reducing intracranial pressure • Less potential for hypovolemia than with mannitol- the diuretic effect is less potent • rapid restoration of intravascular volume, BP and decreases ICP • May have a better effect on cerebral blood flow for a given reduction in ICP. • Safe endpoint (serum sodium around 145- 155) is easily monitored with serial ABGs. • doesn’t need osmolality testing • higher reflection coefficient at the blood brain barrier than mannitol • can be used as a continuous infusion DISADVANTAGES: Need for central venous access • No standards for which concentration to use, or how to give it • Hypokalaemia • Hyperchloraemic acidosis • Hypernatremia • Should not be used if the patient is chronically hyponatremic • Phlebitis • Tissue necrosis if extravasates • central pontine myelinosis if Na+ corrected too quickly in hyponatraemia • Increase in circulating volume with risk of fluid overload. • Coagulopathy (APTT and INR) • Altered platelet aggregation. • May affect normal brain more that injured brain which theoretically may worsen herniation • Rebound intracranial hypertension	Osm (20%) 1100 ADVANTAGES: Still fairly cheap • Rapid effect (onset – minutes, duration – 3 hrs) • Seems to have some sort of rheological benefit (increases red cell deformability) • Acts as a transient volume expander • May have a better effect on cerebral blood flow for a given reduction in ICP. DISADVANTAGES: Unstable in storage: at low temperatures and at altitude, it precipitates. • Medium for bacteria and fungus. • Causes a brief state of volume overload • Causes torrential diuresis and hypovolemia • Causes hyponatremia while in the serum, and hypernatremia after the inevitable diuresis • washes out medullary interstitial gradient - > decreased ability to concentrate urine • Endpoint is serum osmolality(320), which is cumbersome to measure • May cause ICP to "rebound" after prolonged use • should be discontinued if Na+ > 160 or osmolarity > 320mosmol/kg	pH 6.5 (6-7.3) Osm 278 Na 131 Cl 111 K 5 Ca 2 Lactate 29	pH 5.5 Osm 294 Na 140 Cl 98 K 5 Mg 1.5 Acetate 27 Gluconate 23	pH 3.5-6.5 Osm 278 Dextrose penetrates the cells so easily, it cannot contribute to tonicity	Na 140 Cl 128 Albumin 40gm/L (20gm in 500ml)	pH 6.7-7.3 Osm 260 Na 100 Albumin 200gm/L (20gm in 100ml)

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ELECTROLYTES AND BUFFERS

Pending

Pharmacopeia - Electrolytes & Buffers

	POTASSIUM	CALCIUM CHLORIDE	MAGNESIUM SULPHATE	SODIUM BICARBONATE	PHOSPHATE	CALCIUM GLUCONATE
GROUP	Electrolytes and Buffers	Electrolytes and Buffers	Electrolytes and Buffers	Electrolytes and Buffers	Electrolytes and Buffers	Electrolytes and Buffers
CICM Level of Understanding	Level 1	Level 2	Level 1	Level 1	Level 2	Level 2

INTRODUCTION
USES			Pre-eclampsia/eclampsia Hypomagnesemia Premature Labour AMI Torsade de pointes and ventricular dysrhythmias Asthma Cerebral oedema	1. for the correction of profound metabolic acidosis, especially that complicating cardiac arrest 2. for the alkalinization of urine and 3. as an antacid


PHARMACEUTICS (PC)
PC: Chemical			Inorganic Sulphate	inorganic salt
PC: Presentation			Presented as 50% magnesium IV solution (40 mmol in 100mL)	300mg tablets. Clear, colourless sterile solution: 1.26/4.2/9.4% w/v NaHCO3 in aqueous solution 8.4% solution contains 1mmol/ml of sodium and bicarbonate ions, osmolarity of 2000mOsm/L


PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action			Multiple proposed mechanisms 1. Co-factor in enzyme reactions (as a metallo-coenzyme) eg Na+/K+ ATPase activity 2. Energy storage, utilisation, transfer (via role in formation/utilisation of ATP) eg BSL homeostasis 3. Protein and nucleic acid synthesis (stabilises DNA and RNA structure) 4. ↓ membrane excitability (eg. muscles/nerves) 5. ↓ NT release at cholinergic and adrenergic synapses 6. Antagonises Ca2+ activity	Freely dissociates to HCO3- ions (main extracellular buffer) 1gm NaHCO3 will neutralize 12mEq of H+ ions
PD: Route & Doses			Route: PO, IV, IM	Antacid: 600-1800mg as required Alkalinization: 3g PO Q2hrly till urine pH 7 IV: Dose (mmol) = [base deficit (mEg/l) x body weight (kg)] / 3 Half dose administered and reassess acid-base status
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects			CVS: ▪ Peripheraly causes vasodilation and hypotension in high doses ▪ Slows rate of SA node impulse formation and prolongs SA conduction time. ▪ Prolonged PR interval and AV node effective refractory period. RESP: ▪ Bronchodilation • ↓ing cytosolic Ca2+ concentrations. • ↓’d Mg levels → ↑ airway hyper-responsiveness ▪ Attenuates hypoxic pulmonary vasoconstriction CNS: ▪ ↑s effect of CNS depressants and NMBs ▪ CNS depressand and exhibits anticonvulsant properties. ▪ Inhibition of catecholamine released from adrenergic nerve terminal and the adrenal medulla OTHER ▪ Pain on IM injection ▪ Osmotic laxative ▪ Renal vasodilator and diuretic effects. ▪ ↓ed uterine tone and contractility • Competes with Ca2+ at: 1. Membrane L-type VG Ca2+ channels → ↓ [Ca2+] entry 2. Low-affinity Ca2+ binding sites on SR membrane → ↓ [Ca2+] induced [Ca2+] release • ↓ IC [Ca2+] ▪ ↑d placental perfusion ▪ ↑d clotting time of whole blood. ▪ ↓ed thrombin induced platelet aggregation.	CVS: Overcorrection → Metabolic Alkalosis → Myocardial dysfunction and hypoxia due to left shift of O2 dissociation curve RS: Alkalosis reduces pulmonary ventilation CNS: excitability →nervousness, convulsions, muscle weakness, tetany AS: Oral – release of CO2 → belching Metabolic: ↑Na, ↑K, ↓Ca
PD: Side Effects / Toxicity			Toxicity: • Somnolence, areflexia, AV and intraventricular conduction disorder • Progressive muscular weakness • Cardiac arrest • Reversal of toxicity with Calcium administration	Hypernatremia, Hyperosmolar syndromes Irritant to tissues when extravasated → skin necrosis and sloughing


PHARMACOKINETICS (PK)				Data incomplete
PK: Absorption			25-65% oral absorption

PK: Distribution
Protein binding (PK: Distribution)			30% PB
Volume of distribution (PK: Distribution)			Vd 8L/kg

PK: Metabolism			Dissociates into Mg (active component) and Sulphate	React with H+ to yield CO2 and water

PK: Excretion			> 50% excreted unchanged in urine	Renal excretion of bicarbonate and exhalation of CO2
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)


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INDIVIDUAL TABLES

SODIUM BICARBONATE

Pharmacopeia - Electrolytes & Buffers

	SODIUM BICARBONATE
GROUP	Electrolytes and Buffers
CICM Level of Understanding	Level 1

INTRODUCTION
USES	1. for the correction of profound metabolic acidosis, especially that complicating cardiac arrest 2. for the alkalinization of urine and 3. as an antacid


PHARMACEUTICS (PC)
PC: Chemical	inorganic salt
PC: Presentation	300mg tablets. Clear, colourless sterile solution: 1.26/4.2/9.4% w/v NaHCO3 in aqueous solution 8.4% solution contains 1mmol/ml of sodium and bicarbonate ions, osmolarity of 2000mOsm/L


PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Freely dissociates to HCO3- ions (main extracellular buffer) 1gm NaHCO3 will neutralize 12mEq of H+ ions
PD: Route & Doses	Antacid: 600-1800mg as required Alkalinization: 3g PO Q2hrly till urine pH 7 IV: Dose (mmol) = [base deficit (mEg/l) x body weight (kg)] / 3 Half dose administered and reassess acid-base status
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects	CVS: Overcorrection → Metabolic Alkalosis → Myocardial dysfunction and hypoxia due to left shift of O2 dissociation curve RS: Alkalosis reduces pulmonary ventilation CNS: excitability →nervousness, convulsions, muscle weakness, tetany AS: Oral – release of CO2 → belching Metabolic: ↑Na, ↑K, ↓Ca
PD: Side Effects / Toxicity	Hypernatremia, Hyperosmolar syndromes Irritant to tissues when extravasated → skin necrosis and sloughing


PHARMACOKINETICS (PK)	Data incomplete
PK: Absorption

PK: Distribution
Protein binding (PK: Distribution)
Volume of distribution (PK: Distribution)

PK: Metabolism	React with H+ to yield CO2 and water

PK: Excretion	Renal excretion of bicarbonate and exhalation of CO2
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)


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MAGNESIUM SULPHATE

Pharmacopeia - Electrolytes & Buffers

	MAGNESIUM SULPHATE
GROUP	Electrolytes and Buffers
CICM Level of Understanding	Level 1

INTRODUCTION
USES	Pre-eclampsia/eclampsia Hypomagnesemia Premature Labour AMI Torsade de pointes and ventricular dysrhythmias Asthma Cerebral oedema


PHARMACEUTICS (PC)
PC: Chemical	Inorganic Sulphate
PC: Presentation	Presented as 50% magnesium IV solution (40 mmol in 100mL)


PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Multiple proposed mechanisms 1. Co-factor in enzyme reactions (as a metallo-coenzyme) eg Na+/K+ ATPase activity 2. Energy storage, utilisation, transfer (via role in formation/utilisation of ATP) eg BSL homeostasis 3. Protein and nucleic acid synthesis (stabilises DNA and RNA structure) 4. ↓ membrane excitability (eg. muscles/nerves) 5. ↓ NT release at cholinergic and adrenergic synapses 6. Antagonises Ca2+ activity
PD: Route & Doses	Route: PO, IV, IM
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects	CVS: ▪ Peripheraly causes vasodilation and hypotension in high doses ▪ Slows rate of SA node impulse formation and prolongs SA conduction time. ▪ Prolonged PR interval and AV node effective refractory period. RESP: ▪ Bronchodilation • ↓ing cytosolic Ca2+ concentrations. • ↓’d Mg levels → ↑ airway hyper-responsiveness ▪ Attenuates hypoxic pulmonary vasoconstriction CNS: ▪ ↑s effect of CNS depressants and NMBs ▪ CNS depressand and exhibits anticonvulsant properties. ▪ Inhibition of catecholamine released from adrenergic nerve terminal and the adrenal medulla OTHER ▪ Pain on IM injection ▪ Osmotic laxative ▪ Renal vasodilator and diuretic effects. ▪ ↓ed uterine tone and contractility • Competes with Ca2+ at: 1. Membrane L-type VG Ca2+ channels → ↓ [Ca2+] entry 2. Low-affinity Ca2+ binding sites on SR membrane → ↓ [Ca2+] induced [Ca2+] release • ↓ IC [Ca2+] ▪ ↑d placental perfusion ▪ ↑d clotting time of whole blood. ▪ ↓ed thrombin induced platelet aggregation.
PD: Side Effects / Toxicity	Toxicity: • Somnolence, areflexia, AV and intraventricular conduction disorder • Progressive muscular weakness • Cardiac arrest • Reversal of toxicity with Calcium administration


PHARMACOKINETICS (PK)
PK: Absorption	25-65% oral absorption

PK: Distribution
Protein binding (PK: Distribution)	30% PB
Volume of distribution (PK: Distribution)	Vd 8L/kg

PK: Metabolism	Dissociates into Mg (active component) and Sulphate

PK: Excretion	> 50% excreted unchanged in urine
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)


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HARTMANN’S | NORMAL SALINE

Pharmacopeia - IV Fluids

	HARTMANN’s (CSL)	NORMAL SALINE
GROUP	Crystalloid	Crystalloid
CICM Level of Understanding	Level 1	Level 1

INTRODUCTION	Compound sodium lactate	intravenous fluid with 9g NaCl in litre of sterile water. Isotonic crystalloid solution
USES	1. in the treatment of dehydration 2. for the acute expansion of intravascular volume and 3. to provide maintenance fluid and electrolyte requirements in the perioperative period.	1. Initial replacement fluid, in volume depleted or dehydrated patients. Volume depletion may be due to loss of blood, plasma or fluid and electrolytes. 2. Maintenance of hydration during prolonged patient contact time. 3. To keep vein open, as IV route for drugs.


PHARMACEUTICS (PC)	As a clear, colourless sterile solution in 500/1000 ml bags	500 or 1000mls of 0.9% Sodium Chloride solution in a collapsible plastic flask or bag.


PHARMACODYNAMICS (PD)	CVS The haemodynamic effects of Hartmann’s solution are proportional to the prevailing circulating volume and are short-lived. GU Renal perfusion is temporarily restored towards normal in hypovolaemic patients transfused with the crystalloid. Metabolic/other 1 l of one-sixth molar sodium lactate is potentially equivalent to 290 ml of 5% sodium bicarbonate in its acid-neutralizing effect and to 600 ml of 5% glucose in its antiketogenic effect	1. Plasma volume expander 2. Also expands interstitial fluid volume 3. Plasma volume effect is only temporary as most of the saline moves out of the blood vessels quite quickly
PD: Side Effects / Toxicity	The predominant hazard is that of overtransfusion, leading to hypernatraemia, pulmonary oedema, and metabolic alkalosis.	1. Fluid overload 2. hyperchloremic metabolic acidosis 3. increased risk of renal failure compared to balanced solutions 4. Injury to endothelial glycocalyx


PHARMACOKINETICS (PK)
PK: Absorption	IV. BA 100%	IV. BA 100%

PK: Distribution	initially distributed into the plasma but later equilibrates with the extracellular fluid.	~15mins: ISF 750mls Plasma volume 250mls. Not distributed to ICF

PK: Metabolism	- The lactate component is oxidized in the liver to bicarbonate and glycogen over a period of about 2 hours. - This is dependent on cellular oxidative activity, and the mechanism may be depressed by hypoxia and liver dysfunction.	Unmetabolized

PK: Excretion	Excretion Via the urine.	Excreted by kidney Slower than balanced solutions


SPECIAL POINTS	pH 6.5 (6-7.3) Osm 278 Na 131 Cl 111 K 5 Ca 2 Lactate 29	pH 5.0 Osm 308 Tonicity 286 Na 154 Cl 154

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NORMAL SALINE | 5% DEXTROSE

Pharmacopeia - IV Fluids

	NORMAL SALINE	GLUCOSE – 5%
GROUP	Crystalloid	Crystalloid
CICM Level of Understanding	Level 1	Level 1

INTRODUCTION	intravenous fluid with 9g NaCl in litre of sterile water. Isotonic crystalloid solution	intravenous fluid with 50g glucose in litre of sterile water. Hypotonic solution
USES	1. Initial replacement fluid, in volume depleted or dehydrated patients. Volume depletion may be due to loss of blood, plasma or fluid and electrolytes. 2. Maintenance of hydration during prolonged patient contact time. 3. To keep vein open, as IV route for drugs.	1. Maintenance fluid and caloric supply in cases of hypoglycaemia or starvation 2. Fluid replacement along with Insulin in DKA/HHS states 3. Fluid replacement in hypernatremic/ hyperosmolar states


PHARMACEUTICS (PC)	500 or 1000mls of 0.9% Sodium Chloride solution in a collapsible plastic flask or bag.	500 or 1000mls of 5% glucose in a collapsible plastic flask or bag


PHARMACODYNAMICS (PD)	1. Plasma volume expander 2. Also expands interstitial fluid volume 3. Plasma volume effect is only temporary as most of the saline moves out of the blood vessels quite quickly	Glucose replacement Immediately taken up into ISF and Intracellular spaces
PD: Side Effects / Toxicity	1. Fluid overload 2. hyperchloremic metabolic acidosis 3. increased risk of renal failure compared to balanced solutions 4. Injury to endothelial glycocalyx	Fluid overload (less than dextrose) Cerebral edema Hyperglycaemia Electrolyte imbalances (hypokalemia,Mg,P) Extravasation/ Vein irritation / tissue necrosis Severe dehydration if given in diabetics without insulin


PHARMACOKINETICS (PK)
PK: Absorption	IV. BA 100%	IV. BA 100%

PK: Distribution	~15mins: ISF 750mls Plasma volume 250mls. Not distributed to ICF	ICF 670mls ECF 330mls (with ISF 250mls and plasma 80mls).

PK: Metabolism	Unmetabolized	Dextrose is taken into cells and potentially metabolized by multiple pathways, depending on: - Nutritional state - Catabolic or anabolic state - Insulin resistance/DM

PK: Excretion	Excreted by kidney Slower than balanced solutions	Water is excreted via kidney


SPECIAL POINTS	pH 5.0 Osm 308 Tonicity 286 Na 154 Cl 154	pH 3.5-6.5 Osm 278 Dextrose penetrates the cells so easily, it cannot contribute to tonicity

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NORMAL SALINE | 4% ALBUMIN

Pharmacopeia - IV Fluids

	NORMAL SALINE	ALBUMIN 4%
GROUP	Crystalloid	Colloid
CICM Level of Understanding	Level 1	Level 1

INTRODUCTION	intravenous fluid with 9g NaCl in litre of sterile water. Isotonic crystalloid solution	Natural Colloid
USES	1. Initial replacement fluid, in volume depleted or dehydrated patients. Volume depletion may be due to loss of blood, plasma or fluid and electrolytes. 2. Maintenance of hydration during prolonged patient contact time. 3. To keep vein open, as IV route for drugs.	1. Volume replacement 2. Priming of extracorporeal circuits 3. Treatment of hypoalbuminaemic states 4. Replacement fluid during plasma exchange 5. Spontaneous bacterial peritonitis


PHARMACEUTICS (PC)	500 or 1000mls of 0.9% Sodium Chloride solution in a collapsible plastic flask or bag.	- Heat treated human albumin 500ml bottles containing 10g albumin. - Straw-coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 4% is iso-oncotic


PHARMACODYNAMICS (PD)	1. Plasma volume expander 2. Also expands interstitial fluid volume 3. Plasma volume effect is only temporary as most of the saline moves out of the blood vessels quite quickly	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes and drugs. CVS: Dependent on circulating volume status.
PD: Side Effects / Toxicity	1. Fluid overload 2. hyperchloremic metabolic acidosis 3. increased risk of renal failure compared to balanced solutions 4. Injury to endothelial glycocalyx	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI


PHARMACOKINETICS (PK)
PK: Absorption	IV. BA 100%

PK: Distribution	~15mins: ISF 750mls Plasma volume 250mls. Not distributed to ICF	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular

PK: Metabolism	Unmetabolized	Breakdown is predominantly by intracellular lysosome proteases under feedback control

PK: Excretion	Excreted by kidney Slower than balanced solutions	Albumin normally has a T1/2 of 19 days


SPECIAL POINTS	pH 5.0 Osm 308 Tonicity 286 Na 154 Cl 154	Na 140 Cl 128 Albumin 40gm/L (20gm in 500ml)

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MANNITOL | HYPERTONIC SALINE

Pharmacopeia - IV Fluids

	MANNITOL	HYPERTONIC SALINE (3%)
GROUP	Osmotic Diuretic	Crystalloid
CICM Level of Understanding	Level 3	Level 1

INTRODUCTION	an alcohol derived from Dahila tubers (6 carbon sugar) decrease ICP: 0.25g/kg over 15min to 1g/kg PROS & CONS – See BELOW	Hypertonic Crystalloid PROS & CONS – See BELOW
USES	1. reduce CSF volume -> reduce ICP 2. preserve renal function during perioperative period in jaundice patients under going major vascular surgery. 3. acute management of glaucoma 4. bowel prep 5. initiate diuresis in transplanted kidney 6. treatment for rhabdomyolysis	1. Treatment of severe, symptomatic hyponatraemia 2. Management of raised ICP 3. In nebulized form as an expectorant


PHARMACEUTICS (PC)	sterile solution 10-20% in water	3%, 5% and 23.4% Should be administered through CVC due to thrombophlebitis


PHARMACODYNAMICS (PD)	MOA: • increases the osmolarity of the glomerular filtrate -> increasing urinary volume • decreases CSF volume & pressure by (1) decreasing rate of CSF production (2) withdrawing brain extracellular water across the BBB into plasma	MOA: Increased serum sodium concentration. Leads to increase in serum tonicity, leading to diffusion of intracellular fluid into the intravascular space, decreasing cerebral oedema. CNS: Decreased cerebral oedema, decreased ICP, may cause central pontine myelinolysis CVS: Fluid shift into intravascular compartment increases plasma volume and may improve preload ? increase cardiac output ? increase BP
PD: Side Effects / Toxicity		1. Central pontine myelinolysis 2. Hypernatraemia and hyperosmolarity 3. NAGMA 4. Thrombophlebitis 5. Seizures


PHARMACOKINETICS (PK)
PK: Absorption		IV.

PK: Distribution

PK: Metabolism	Unmetabolized	Unmetabolized

PK: Excretion		renally excreted


SPECIAL POINTS	Osm (20%) 1100 ADVANTAGES: Still fairly cheap • Rapid effect (onset – minutes, duration – 3 hrs) • Seems to have some sort of rheological benefit (increases red cell deformability) • Acts as a transient volume expander • May have a better effect on cerebral blood flow for a given reduction in ICP. DISADVANTAGES: Unstable in storage: at low temperatures and at altitude, it precipitates. • Medium for bacteria and fungus. • Causes a brief state of volume overload • Causes torrential diuresis and hypovolemia • Causes hyponatremia while in the serum, and hypernatremia after the inevitable diuresis • washes out medullary interstitial gradient - > decreased ability to concentrate urine • Endpoint is serum osmolality(320), which is cumbersome to measure • May cause ICP to "rebound" after prolonged use • should be discontinued if Na+ > 160 or osmolarity > 320mosmol/kg	Osm 900 Na 450 Cl 450 ADVANTAGES: Cheap • Stable in storage • Easy to transport (small volume) • Very rapid effect (peak @ 10 min, lasts 1 hour) • Seems to have some sort of intrinsic antiinflammatory effect (may decrease MODS) • May also have some rheological benefits At least as potent as mannitol when it comes to reducing intracranial pressure • Less potential for hypovolemia than with mannitol- the diuretic effect is less potent • rapid restoration of intravascular volume, BP and decreases ICP • May have a better effect on cerebral blood flow for a given reduction in ICP. • Safe endpoint (serum sodium around 145- 155) is easily monitored with serial ABGs. • doesn’t need osmolality testing • higher reflection coefficient at the blood brain barrier than mannitol • can be used as a continuous infusion DISADVANTAGES: Need for central venous access • No standards for which concentration to use, or how to give it • Hypokalaemia • Hyperchloraemic acidosis • Hypernatremia • Should not be used if the patient is chronically hyponatremic • Phlebitis • Tissue necrosis if extravasates • central pontine myelinosis if Na+ corrected too quickly in hyponatraemia • Increase in circulating volume with risk of fluid overload. • Coagulopathy (APTT and INR) • Altered platelet aggregation. • May affect normal brain more that injured brain which theoretically may worsen herniation • Rebound intracranial hypertension

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ALBUMIN

Pharmacopeia - IV Fluids

	ALBUMIN 4%	ALBUMIN 20%
GROUP	Colloid	Colloid
CICM Level of Understanding	Level 1	Level 1

INTRODUCTION	Natural Colloid	Natural Colloid
USES	1. Volume replacement 2. Priming of extracorporeal circuits 3. Treatment of hypoalbuminaemic states 4. Replacement fluid during plasma exchange 5. Spontaneous bacterial peritonitis	1. Hypoproteinaemia 2. Shock 3. Burns 4. ARDS 5. Plasma exchange


PHARMACEUTICS (PC)	- Heat treated human albumin 500ml bottles containing 10g albumin. - Straw-coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 4% is iso-oncotic	- Heat treated human albumin 200ml bottles containing 200g/L. Straw coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 20% is hyperoncotic with approximately the equivalence of approximately 4x its volume in plasma


PHARMACODYNAMICS (PD)	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes and drugs. CVS: Dependent on circulating volume status.	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes, Mg2+ and Ca2+, and acidic drugs. CVS: Dependent on circulating volume status. Raised plasma oncotic pressure may lead to 3x the administered volume being dragged into the plasma within 15min.
PD: Side Effects / Toxicity	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI


PHARMACOKINETICS (PK)
PK: Absorption

PK: Distribution	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular

PK: Metabolism	Breakdown is predominantly by intracellular lysosome proteases under feedback control	Breakdown is predominantly by intracellular lysosome proteases under feedback control

PK: Excretion	Albumin normally has a T1/2 of 19 days	Albumin normally has a T1/2 of 19 days


SPECIAL POINTS	Na 140 Cl 128 Albumin 40gm/L (20gm in 500ml)	pH 6.7-7.3 Osm 260 Na 100 Albumin 200gm/L (20gm in 100ml)

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4% ALBUMIN

Pharmacopeia - IV Fluids

	ALBUMIN 4%
GROUP	Colloid
CICM Level of Understanding	Level 1

INTRODUCTION	Natural Colloid
USES	1. Volume replacement 2. Priming of extracorporeal circuits 3. Treatment of hypoalbuminaemic states 4. Replacement fluid during plasma exchange 5. Spontaneous bacterial peritonitis


PHARMACEUTICS (PC)	- Heat treated human albumin 500ml bottles containing 10g albumin. - Straw-coloured clear solution. - Shelf life of 4 years - Should be stored <30’C - Heat treated at 60’C for 10 hours (pasteurized) and incubated at low pH - Contains sodium chloride and water for injection - 4% is iso-oncotic


PHARMACODYNAMICS (PD)	MOA: Albumin accounts for 70% of plasma oncotic pressure. Carrier of hormones, enzymes and drugs. CVS: Dependent on circulating volume status.
PD: Side Effects / Toxicity	1. Risk of Creutzfeldt Jakob Disease and Parvovirus B19 (Resistant to heat treatment) 2. Pulmonary oedema 3. Has been associated with myocardial depression 4. Contraindicated in TBI


PHARMACOKINETICS (PK)
PK: Absorption

PK: Distribution	Under normal circumstances 40% of albumin is intravascular and 60% is extravascular

PK: Metabolism	Breakdown is predominantly by intracellular lysosome proteases under feedback control

PK: Excretion	Albumin normally has a T1/2 of 19 days


SPECIAL POINTS	Na 140 Cl 128 Albumin 40gm/L (20gm in 500ml)

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Y04. Pharmacopeia: Intravenous Fluid Pharmacology

CICMWrecks Tables (Click to Open)

MASTER TABLES

INTRAVENOUS FLUIDS

Pharmacopeia - IV Fluids

ELECTROLYTES AND BUFFERS

Pharmacopeia - Electrolytes & Buffers

INDIVIDUAL TABLES

SODIUM BICARBONATE

Pharmacopeia - Electrolytes & Buffers

MAGNESIUM SULPHATE

Pharmacopeia - Electrolytes & Buffers

HARTMANN’S | NORMAL SALINE

Pharmacopeia - IV Fluids

NORMAL SALINE | 5% DEXTROSE

Pharmacopeia - IV Fluids

NORMAL SALINE | 4% ALBUMIN

Pharmacopeia - IV Fluids

MANNITOL | HYPERTONIC SALINE

Pharmacopeia - IV Fluids

ALBUMIN

Pharmacopeia - IV Fluids

4% ALBUMIN

Pharmacopeia - IV Fluids

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