intravenous fluid therapy- a pharmacist’s challenge
TRANSCRIPT
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
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
FURTHER READING
Any questions?
REFERENCES• NICE guidelines and elearning available at http://elearning.Nice.Org.Uk/
• British consensus guidelines on intravenous fluid therapy for adult surgical
patients GIFTASUP available at
http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf
• Fife Fluid Guidelines 2013 available at
https://www.eemec.med.ed.ac.uk/pages/fluid-therapy
• Intravenous Fluid Therapy- what pharmacist need to monitor. Staples et al.
Hospital Pharmacist 2008;15:277-282
• A comparison of albumin and saline for fluid resuscitation in the intensive
care unit. The SAFE study investigators. N engl J med 2004; 350:2247-2256
• Hydroxyethyl starch or saline for fluid resuscitation in intensive
care. Myburgh et AL N engl J med 2012, 367:1901-1911
REFERENCES
• Four phases of intravenous fluid therapy: a Conceptual model. Hoste et al. BJA,
2014; 1-8.
• Fluid therapy in critical illness. Edwards and Mythen. Extreme Physiology and
Medicines 2014; 3:16
• Context- sensitive fluid therapy in critical illness. Tatara. Journal of Intensive Care,
2016; 4:20
• Fluid Management for Critically Ill Patients: A Review of current state of fluid
therapy in the Intensive Care Unit. Frazee and Kashani. Kidney dis 2016; 2:64-71
• Resuscitation Fluids. Myburgh and Mythen. NEJM, 2013; 13:1243-1251
• Choices in fluid type and volume during resuscitation:impact on patient outcomes.
Lira and Pinksy. Annals of Intensive Care, 2014; 4:38.