Intravenous fluid therapy- A pharmacist’s challenge

Intravenous fluid therapy- A pharmacist’s

challenge EMMA BOXALL

SALFORD ROYAL NHS FOUNDATION TRUST

FLUID PRESCRIPTIONS

MUST BE GIVEN SAME

STATUS AS DRUG

PRESCRIPTION

1 in 5 patients suffer morbidity due to

inappropriate fluid therapy

NICE Fluids Dec 2013

OBJECTIVES OF SESSION

• Understanding of pathophysiology

• Types of fluid replacement

• Assessment of the fluid balance

• Clinical scenarios with guides to fluid

replacement

The right amount

of the right fluid

at the right time

Total body water

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THE NORMAL COMPOSITION OF MAJOR BODY FLUID COMPARTMENTS

Plasma (mmol/L) Interstitial Fluid (mmol/L)

Intracellular Fluid (mmol/L)

Na+ 142 144 10

K+ 4 4 160

Ca 2+ 2.5 2.5 1.5

Mg 2+ 1.0 0.5 13

Cl- 102 114 2

HCO3- 26 30 8

PO4 2- 1.0 1.0 57

SO4 2- 0.5 0.5 1.0

Organic acid 3 4 3

Protein 16 0 55

• Haemodynamic forces

• changes in blood volume affect

cardiac output and circulation

• autonomic control

• Starlings hypothesis

• if hydrostatic pressure >osmotic

pressure, fluid leaves capillary

and vice versa

GLYOCALYX LAYER

Myburgh and Mythen 2013

REVISED PRIMARY FORCES

Lira and Pinsky 2014

FLUID BALANCE

WATER BALANCE

• Intake controlled by thirst

• Excretion controlled by ADH (vasopressin)

• Osmolarity

• Plasma osmolarity >280 mOsmol/kg

• Sensitises central osmoreceptors → stimulates thirst response

• ADH secreted →water reabsorption

• Circulating volume

• blood volume (atrial stretch receptors) and BP (baroreceptors)

• ADH secretion → water reabsorption

The right amount

of the right fluid

at the right time

ASSESSMENT OF FLUID BALANCE

History

Clinical Examination

Laboratory assessment

• Good patient history

• Check co-morbidities

• Medication

• Previous fluid intake

• Fluid loss (previous, current and ongoing)

History

DAILY REQUIREMENTS (GIFTASUP)

• Water 25-35 ml/kg (30)

• Sodium approx 1 mmol/kg

• Potassium approx 1 mmol/kg

• Calories minimum 400 calories

(i.E. 100 g dextrose)

(CALORIES HELP TO DEAL WITH ELECTROLYTES NORMALLY)

DAILY SODIUM REQUIREMENTS

• 0.9% is 9g/L

• WHO intake recommendations- 5g/day of salt

0.47g NaCl/34g packet

18g 2L NaCl/day

39 packets of crisps!

ASSESSING THE PATIENT

From NICE elearning on fluids

• Weight

• BP

• Capillary refill time

• Urine output

• Postural hypotension

• Presence of peripheral oedema or postural hypotension

• More invasive techniques such as CVP

• SIGNS OF FLUID DEPLETION • Thirst

• Primary stimulus

• Missing in some patients

• Skin turgor

• Pulse

• Sunken eyes

• Furrowed tongue

• Weight change

• Oliguria• (U/o < 0.5ml/kg/hr)

Clinical Examination

ASSESSING THE PATIENT• Has the patient been starved (e.g. Pre op)?

• Do they have an iv infusion in progress?

• Are there any reasons to expect excess losses (e.G. Due to type of surgery, burns etc)?

• Diuretics?

• Pyrexia?

• Vomiting / ng tube

• Diarrhoea / bowel prep

• ‘Third space’ losses

• Urea

• Creatinine

• Electrolytes

• Serum osmolality (mosmol/L)

= 2(k++na+) + glucose + urea

• Normal = 290 mosmol/L

• Haematocrit, haemoglobin

Laboratory Assessment

DOES THE PATIENT NEED IV

FLUID?

What phase of their illness are

they in?

BRITISH CONSENSUS GUIDELINES ON INTRAVENOUS FLUID THERAPY

FOR ADULT SURGICAL PATIENTS GIFTASUP

Jeremy Powell-tuck (chair), Peter Gosling,

Dileep N lobo, Simon P Allison, Gordon L Carlson, Marcus Gore, Andrew J

Lewington,

Rupert M Pearse, Monty G Mythen

5 RS

• RESUSCITATION –

• MAINTENANCE –WATER AND ELECTROLYTES

• REPLACEMENT AND REDISTRIBUTION

• REASSESSMENT

4 PHASES OF IV FLUID THERAPY

Hoste et al 2014

Are they hypovolaemic and in need of urgent fluid resuscitation?

• Key indicators

• Systolic blood pressure of less than 100 mmHg

• Heart rate is more than 90 beats per minute

• Capillary refill time is more than 2 seconds or peripheries are cold to the

touch

• Resp rate more than 20 breaths per min

• NEWS score is 5 or more

• Passive leg raising suggest fluid responsiveness

• Fluid balance charts

• Weight

ASSESSMENT OF HYPOVOLAEMIA

Acute circulatory failure

Evidence of fluid loss

Early phase of sepsis

Fluid administration

Fluid challenge

(mini)

Passive leg raising

test Cardiac

monitoring

Yes NO

RAISED LEG TEST

29

Which Patient?

In the event of hypotension and/or lactate > 4 mmol/L (36 mg/dL) deliver an initial minimum of 20 mL/kg of crystalloid (or colloid equivalent).

Surviving Sepsis Campaign: International guidelines for

management of severe sepsis and septic shock: 2008*R. Phillip Dellinger, MD; Mitchell M. Levy, MD; Jean M. Carlet, MD; Julian Bion, MD;

Margaret M. Parker, MD; Roman Jaeschke, MD;et a

Crit Care Med 2008

FLUID BOLUS

• GLASSFORD ET AL. CRITICAL CARE 2014 18:696

Pros and cons of crystalloid leading to under or over resuscitation in clinical

practice

Too Little Too Much

Tissue hypoxygenation Tissue oedema and hypoxygenation

Risk of AKI Compartment syndromes and renal dysfunction

Lactate and unmeasured anion acidosis Hyperchloremic metabolic acidosis and risk of hypernatremia

Gastrointestinal disturbances Anastomotic leakage, diarrhoea and other GI disturbances

Pulmonary odema, hepatic congestion and injury

Prolonged mechanical ventilation

ROUTINE MAINTENANCE

TYPE OF FLUID REPLACEMENT

Intravenous Fluids

Crystalloids Colloids

Gelatins

Blood products

Packed red cells

Platelets, FFP

Albumin

Glucose

Various

strength

Sodium chloride

0.9%/Balanced

solution

Blood and blood products

Whole blood used to replace the loss of wholeblood and to restore Hb

Packed red blood cells improve oxygen carrying capacity of blood while preventing fluid overload

Fresh frozen plasma not used as a first choice volume expander in shock - usually reserved for multiple coagulation defects, rapid reversal of warfarin, selected immunodeficiencies

COLLOIDS

• substances with large molecular weights which contribute to oncotic pressure at the microvascular endothelium

• confined to the plasma

• produce a greater expansion of plasma (by attracting H2O from the ICF)

• efficacy depends onshape charge of the molecule

size porosity of capillary endothelium

• Traditionally used for hypovolaemia, requirement assessed by hr/bp/CVP response 15 mins after a 200ml bolus

• unsuitable for treatment of dehydration

COLLOIDS – GELATINS

• Derived from animal gelatin (bovine)

• Wide variation in molecule size

• Gelofusin – succinylated gelatin (4.5%)

• Cheap. Provides good initial volume expansion

• Stimulates histamine release

• Has plasma t1/2 of 2-4 hours.

• Intravascular persistence is low

• ?Risk of bleeding due to dilution of clotting factors

• Sodium content of gelofusine-154 mmol/L

ESTERIFIED STARCHES (HYDROXYETHYLSTARCH)

• 4 PRODUCTS – DIFF MOLECULAR WT

• VOLUVEN, ELOHAES, HAES-STERIL, HEMHES

• PLASMA T1/2 OF 24 HOURS SO REMAIN IN THE BODY FOR

PROLONGED PERIODS.

• CAN CAUSE HYPERSENSITIVITY REACTIONS INC ITCHING

• CHEST 2012

THE CRYSTALLOID VERSUS HYDROXYETHYL STARCH TRIAL

(CHEST, 2012)• Blinded administration of up to 50 ml/kg body weight/day HES versus

sodium chloride in adult patients requiring fluid resuscitation in ICU

• The primary endpoint of all-cause mortality at 90 days was 17% in the

sodium chloride 0.9% group and 18% in the HES group.

• Secondary endpoints revealed an association between HES use and

acute kidney injury and a 21% relative risk increase for renal

replacement therapy

•Reinforced by CRISTAL 2013

HUMAN ALBUMIN SOLUTION (HAS)

• Prepared from whole blood

• Contains soluble proteins and electrolytes but no clotting factors

• Can be given without regard to recipients blood group

• Suspended in 0.9% sodium chloride

4.5%Isotonic

Volume replacementAscites?Burns

20%Hypertonic

Volume expanderHypo-oncotic intravascular

volumeDepletion with oedema

• compared the effects of 4% albumin versus

sodium chloride 0.9% in 6,997 critically ill patients

• no difference in the primary outcome (all-cause

mortality at 28 days)

• subgroup analysis revealed a possible association

between the use of albumin and increased

mortality in patients with traumatic brain injury

TYPE OF FLUID REPLACEMENT

Intravenous Fluids

Crystalloids Colloids

Gelatins

Blood products

Packed red cells

Platelets, FFP

Albumin

Glucose

Various

strength

Sodium chloride

0.9%/Balanced

solution

FLUID CONTENT OF THE BODY

Staples et al 2008

IV SOLUTIONSSOLUTION NA+ CL- K+ CA+2 HCO3- GLU

GLUCOSE 0 0 0 0 0 50

NACL 154 154 0 0 0 0

HARTMANNS 131 111 5 2 29 0

PLASMALYTE 141 98 4-5 5 26 0

DEX/SAL WITH 40MMOL KCL 31 31 40 0 0 40

TARGET FOR 70KG 70 70 70 50-100G

Plasma 142 102 4 2.5 26

CRYSTALLOIDS

• Iso-osmotic with plasma.

• Distribution determined by sodium concentration

• Contain low molecular weight salts or sugar dissolved in water

• Several times more crystalloid than colloid is required to achieve the same degree of vascular filling

• Crystalloid solutions move rapidly into the interstitial compartment

• Crystalloid resuscitation leads to interstitial oedema

GLUCOSE 5%

• Electrolyte free, disperses through ICF and ECF as water. • Very small % remains in blood after distribution

• Source of energy/nutrition• 1L provides 200kcal on metabolism

• No risk of anaphylaxis

• Can cause water intoxication, hyponatraemia, hyperglycaemia

• Use increased concentration (20/50%) for nutrition. Note 50% very irritant, central line only

• Used for:• Immediate hydration

• Supply of basal H2O requirements over and above electrolyte requirements

• Drug adminstration

SODIUM CHLORIDE 0.9%

• Disperses through out ECF not ICF

• Used to replace blood loss requires 3 x vol of blood lost

• Can cause hyperchloraemic acidosis

• Fluid of choice in hypochloraemia eg due to vomiting

• Risk of hypernatraemia if pt has na retention

• Daily requirement of 70-80mmol is normal

• Consider excess losses through sweat/GI tract

• 20% remains intravascular at 1 hour

• Common in drug preparations

• 154mmol/L Na and Cl

BALANCED SOLUTIONS

• 4 large observational studies and a single centre quality improvement initiative have demonstrated associations and superior clinical outcomes and specifically lower incidence of AKI and mortality when compared to isotonic sodium chloride

• Shaw et al: major complications, mortality and resource utilization after open abdominal surgery

• Less electrolyte disturbance

• Fewer acidosis investigations

• Fewer blood transfusions

• Less renal failure requiring dialysis

• Fewer interventions

• Less postoperative infection

• Behaves as sodium chloride 0.9% in distribution

• Electrolyte content mimics ECF

• Is isotonic (pH 6.7)

• Hartmanns/Compound Sodium Lactate/Ringers

• 131mmol Na+, 5mmol K+, 2mmol Ca2+, 111mmol Cl- per litre

• Plasmalyte- chloride 98 mmol

• Used for replacing fluid losses from stoma/diarrhoea, hypovolaemia due to blood loss, fluid maintenance

• Lactate is metabolised and acts as a buffer to acidosis

• Incompatible with some drugs eg amiodarone

Choice for resus and replacement

GLUCOSE 4% /SODIUM CHLORIDE 0.18%

• Isotonic solution that provides 160kcal/L

• 20% sodium chloride and 80% free water

• Useful where fluid depletion from all compartments eg

diabetes insipidus

• Licensed for sc administration

• Useful for maintenance but should not be used for

resuscitation or replacement

• Risk of hyponatraemia, especially in the elderly

Choice for maintenance

SODIUM BICARBONATE

• Available as 1.26%, 1.4%,1.8%, 2.7% 4.2% and 8.4%

• Isotonic (1.26%) used to correct acidosis assoc. With renal failure or to induce forced alkaline diuresis.

• Hypertonic (8.4%) used to raise pH>7.0 in severe acidosis.

• 8.4% is 1mmol/ml Na+ and HCO3-

• Metabolic acidosis to restore pH

HOW MUCH VOLUME?

Weight (kg) Fluid ml/day Fluid ml/hr

30-39 1000 40

40-59 1500 63

60-79 2000 83

>80 2500 104

The right amount

of the right fluid

at the right time

REMEMBER DRUG INFUSIONS

Phosphate polyfusor contains 80mmol of sodium

Phosphate Sandoz 20 mmol per tablet

Soluble paracetamol upto 130- 150mmol /day

Piperacilin/tazobactam 9.12 mmol per 4.5g vial

REASSESSMENT

• Additional cardiac monitoring

• Do they still need it?

• Is the oral route available?

1. 56 year of female undergoing elective major abdominal

surgery who has a major bleep in theatres

2. A post-operative patient with septicaemia and septic

shock

3. 18 year old male who has several open wounds following

a road traffic accident.

4. 45 year old with alcoholic liver disease, ascites and

hypoalbuminaemia.

5. 75 year old gentleman admitted from the medical ward

suffering from dehydration secondary to over diuresis

with frusemide.

CASE STUDIES

Case Studies

56 YEAR OLD FEMALE UNDERGOING

ELECTIVE MAJOR ABDOMINAL SURGERY

WHO HAS A MAJOR BLEED IN THEATRES

Weight 40 kg.

Case Studies

A post-operative patient with

septicaemia and septic shock

Patients weight is 105 kg

How would you assess effects?

POST MAJOR SURGERY• Increased output due to drains from surgical site

• Increase GI output• Ileostomy• Diarrhoea (due to abx/feed)• Ponv

• Increased insensible losses• Hyperventilation• Pyrexia / sweating

• Hypotension – due to hypovolaemia or epidural

• Balanced solution

• Adjustment dependent on sodium

• Excessive need for intravascular volume replacement may imply internal bleeding

Case Studies

18 year old male who has several

open wounds following a road

traffic accident.

BURNS PATIENTS

• Require lots more fluid depend on the type

and extend of the burns

• Various formulas

• Lots of different types of burns

• Inhalation injuries

Case Studies

45 year old with alcoholic liver

disease, ascites and

hypoalbuminaemia.

Case Studies

75 year old gentleman admitted to

the medical ward suffering from

dehydration secondary to over

diuresis with frusemide.

The right amount

of the right fluid

at the right time

PRINCIPLES OF FLUID REPLACEMENT• Fluids should be administered with same cautions

that is with any IV drug• Identify the fluid that is most like to be lost and

replace it in equivalent volume• 5 basic principles should be considered

• Fluid lost should be replaced• Future abnormal losses should be allowed for.• Normal daily requirements should be

maintained• Daily weighing aids in fluid balance

management• Consider serium sodium osmolarity and acid base

status when selecting fluid

WHAT DO WE OFTEN DO?

We give lots of fluid, lots of sodium chloride

Kidneys can’t excrete sodium load

Chloride causes renal vasoconstriction and exacerbates fluid retention and oedema

Leaky capillaries in sick patients exacerbate RAAS/ADH activity and oedema worsens

We don’t give much potassium

Potassium depletion reduces ability to excrete sodium

We don’t give many calories

Calories help the cells to maintain fluid homeostasis

Intravenous fluid therapy- A pharmacist’s challenge

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