Crystalloid Versus Colloid Solutions:

Optimizing Outcomes

Karthik Raghunathan, MD MPH Assistant Professor

Anesthesiology and Critical Care Medicine Duke University. Durham, NC

Optimizing Outcomes ?

Right

– Type of Fluid

– Amount of Fluid

– Time of Infusion

• WHAT FLUID

• HOW MUCH and WHEN

WHY

DISCLOSURES

• RELEVANT TO “FLUIDS”– 2014 APSF / ASA Endowed Research Award– 2014 Baxter IIT

WHAT TYPE OF FLUID

ON THE INJECTION OF SALINE SALTS INTO THE VEINS – DR. THOMAS LATTA OF LEITH

“restoring the natural current in veins and arteries … may be accomplished by injecting a weak saline solution into the veins of the patient”

“The most wonderful and satisfactory effect is the immediate consequence of the injection.”

“ Whenever the pulse fails … fluid ought to be thrown in … from five to ten pounds in an adult … quantity necessary will probably depend upon the quantity of serum lost.”

“The solution that was used consisted of two drachms of muriate, and two scruples of carbonate of soda to sixty ounces of water. It was at a temperature of 108 to 110 degrees”

Dr. Lewins - London Medical Gazette

1832

CASE REPORT IN 1833 - CHOLERAFirst patient was an “aged female”…“… had apparently reached the last moments of her earthly existence, and now nothing could injure her…”“the basilic vein was used…”“resolved to throw the fluid immediately into the circulation… proceeded with much caution”

IT WORKS !

“… soon the sharpened features, and sunken eye, and fallen jaw,

pale and cold, bearing the manifest impress of death’s signet,

began to glow with returning animation”

“the pulse, which had long ceased, returned to the wrist…”

“in the short space of half an hour, when six pints had been

injected … she expressed in firm voice that she was free from all

uneasiness, actually became jocular, and fancied all she needed

was a little sleep; her extremities were warm, and every feature

bore the aspect of comfort and health…”

“ This being my first case, I fancied my patient secure, and from my great need of a little repose, left her in charge of the hospital surgeon …”

“but I had not been long gone, ere the vomiting and purging recurring, soon reduced her to her former state of debility. I was not apprised of the event …”

“she sunk in five and a half hours after I left her”

FOR A WHILE …

“A suitable clinical investigation is required…

• the mass of the profession is unable to decide;

• and thus, instead of any uniform mode of

treatment, every town and village has its

different system or systems,

• while the daily lists of mortality proclaim the

general inefficiency of the whole.“

SOUND FAMILIAR ?

EDITORIAL1833

• Serendipitous substitution of

water in the Lab with tap

water supplied by the New

River Water Co.

• RINGER’S SOLUTION =

optimal electrolyte

concentration required to

maintain contractions in frog

heart muscles !!

Sidney Ringer1880

“ISO”-TONICITY

A = Isotonic B = Hypotonic C = Hypertonic

Hartog Hamburger 1883

Alexis Hartmann 1930

Hartmann's Solution (IN THE UK)~

Ringer’s Lactate (IN THE USA)

TO RECAP …

• IV FLUID THERAPY STARTED IN THE 1830s

• THE FIRST FLUIDS WERE CRYSTALLOIDS – MYSTERIOUS SALT SOLUTION - 1832– RINGER’S LACTATE - 1880s– ISOTONIC SALINE - 1880s

20TH CENTURY WARAGAINST EACH OTHER

NOT CHOLERA!ALBUMIN

MORE WARS MORE “Blood Substitutes”

HYDROXYETHYL STARCH SOLUTIONS

INTERESTING ALTERNATIVES

Fluids IN THE ICU around the world

Finfer (2010) Crit Care 14; R185

CRYSTALLOID VERSUS COLLOIDWHAT IS THE DIFFERENCE

• THE “STARLING” MODEL

– BALANCE OF FORCES

DETERMINES

DISTRIBUTION OF FLUIDS

ACROSS VASCULAR

COMPARTMENTS

FORCES DETERMINE FLUID DISTRIBUTION

Direction of flow through capillaries

Pc: Capillary hydrostatic pressure

mean ~ 17 mmHg

Pi: Interstitialhydrostatic pressure

~ 6 mmHg

Pc > 17 Pc < 17

NetOutflow

NetInflow

COPc (28)

COPi (5)

Arterial end Venous end

Hypotonic Fluid:Distributes to TBWProportions Unchanged

Isotonic Fluid:Distributes to ECCand later to TBW

TBW = Total Body Water (“the full pie”) 60% of IBW

Blood:Distributes toIV space

Colloid: remainsintravascular until metabolized;; but with capillary leak equilibrates to ECC

Hypertonic Fluids:Recruits intracellularand interstitial fluidto intravascular space

BEFORE INFUSION

WHERE FLUIDS GO STARLING’S THEORY

ECC = Extra Cellular Compartment1/3rd of TBW = 20% of IBW Blue = ECF 15%IBW;; Red = IV 5%IBW

ICC = Intra Cellular Compartment2/3rd of TBW = 40% of IBWYellow = ICF

GREAT THEORY: DOES IT WORK?

Saline versus Albumin Fluid Evaluation Study - 2004

• Population• Intervention

– 4% Albumin (n=1414)

• Control – Isotonic Saline

(n=1443)

• Outcome– Survival at 28-days

• Conclusion– Similar Outcomes

ANZICS group

Finfer S. et al NEJM 2004

Hydroxyethyl Starch or Saline CHEST - 2012

• Population• Intervention

– HES (n=3315)

• Control – Isotonic Saline

(n=3336)

• Outcome– Survival at 90-days

• Conclusion– Similar Mortality– MORE RENAL INJURY

with HES

Myburgh et al (2012) NEJM

Survival

PROBLEMS WITH STARCH

HES vs Ringers Acetate

Was CHEST underpowered FOR A MORTALITY OUTCOME?

0 10 20 30 40 500

2

4

6

8

10

CHEST

6S

Observed (prespecified) subgroup mortality (%)

HES

- co

mpa

rato

r mor

talit

y di

ffere

nce

(%)

Hazard maybe related to sickness

SAFETY WARNINGS ON STARCH

BUT WHY USE COLLOIDS AT ALL …

NOT JUST WHAT FLUID YOU GIVE

WHO ARE YOU GIVING IT TO COLLOIDS HAVE A MUCH LOWER VOLUME EFFECT WHEN GIVEN TO HYPERVOLEMIC PATIENTS

BOTH TYPES OF FLUIDS LEAVE THE VASCULAR SPACE WHEN GIVEN TO HYPERVOLEMIC PATIENTS

Woodcock TE, Woodcock TM. Br J Anaes 2012;; 108:384–394.

THERE IS NO ABSOPRTION

REVISED THEORY

THE REVISED STARLING MODEL

ENDOTHELIAL GLYCOCALYX IS KEY

Hypervolemia drives up hydrostatic pressure and damages the glycocalyx

Myburgh 2013. N Engl J Med 2013;;369:1243-­51

KEY FEATURES OF THE EGL

• Barrier is between blood and the capillary wall• Barrier resists fluid and solute filtration to varying degrees

depending on the tissue (marrow = free filtration; brain = no filtration)

• Oncotic gradient exists across the Endothelial Glycocalyx Layer rather than across the vessel wall

• Plasma proteins, including albumin, leak into the ISF via a relatively small number of large pores

• SO BOTH CRYSTALLOIDS AND COLLOIDS WILL LEAK IN VARIOUS DISEASE STATES = NO DIFFERENCE IN EFFICACY IN SICKER PATIENTS

Woodcock TE, Woodcock TM. Br J Anaes 2012;; 108:384–394.

SUMMARYCRYSTALLOIDS v COLLOIDS

• EFFICACY DIFFERENCES ARE NOT SIGNIFICANT – Colloids have 1.5x more efficacy (not 3x)

• SAFETY DIFFERENCES ARE SIGNIFICANT – STARCH IS LESS SAFE

• COST DIFFERENCES ARE SIGNIFICANT – COLLOIDS ARE 16-50x more expensive

• HENCE, COLLOIDS HAVE VERY LIMITED INDICATIONS– NO SURVIVAL BENEFIT AMONG SICKER PATIENTS

SO WHAT IS THE RIGHT QUESTION

CRYSTALLOIDS VERSUS COLLOIDS

CRYSTALLOID CHLORIDE-LIBERAL

VERSUS

CRYSTALLOID CHLORIDE-RESTRICTIVE

TYPES OF CRYSTALLOIDS

DIFFERENCES BASED ON

• CHLORIDE CONTENT

– PLASMA ~ 95-105 mEq /L

• STRONG ION

DIFFERENCE (SID)

– Sodium (140)

– Chloride (100)

– SID = 40

SALT INTOLERANCE FIRST DESCRIBED IN EARLY 20TH CENTURY

Coller FA et al. The replacement of Sodium Chloride in Surgical Patients.

Annals of Surgery 1938 Oct;; 108(4): 769-­82.

PROBLEMS WITH CHLORIDE-LIBERAL FLUIDS

36 bags of chips = 1L ISS

WHAT MAKES SALINE BAD

HYPERCHLOREMIA

SO ISOTONIC SALINE YES OR NO ?

• SPLIT = NO DIFFERENCE IN KIDNEY INJURY– PATIENTS GOT SMALL AMOUNTS (<2L)

• There is an association between resuscitation with isotonic saline and undesirable effects compared to balanced crystalloids (e.g. Ringer’s, Plasma-Lyte) – Hyperchloremia PLUS decrease in the plasma strong

ion difference = Metabolic Acidosis – Reduced cardiac contractility, decreased renal

perfusion, reduced gastric blood flow, and impaired gastric motility

• SALINE USEFUL in ‘Neuro’ and ‘hypochloremic states’

WHEN TO INFUSE FLUIDS

Assessment and MonitoringWhen is Fluid Required?

• WHEN THERE IS INADEQUATE CIRCULATING VOLUME• Traditional Nursing evaluation of Fluid Requirements have focused on

assessment of HR, BP, Urine Output • Changes in HR are often skewed or impaired in the acutely or

chronically ill (by beta blockers or co-morbid cardiovascular pathologies)

• Changes in Urine Output are also neither sensitive or specific markers of hypovolemia in several disease states (such as around surgery)

• Activation of pain pathways, changes in body temperature may distort interpretations of volume status

• Finally, volume deficits may not become apparent until losses exceed 10% body weight

http://ht.edwards.com/resourcegallery/products/mininvasive/pdfs/stroke_volume_variation.pdf

WHAT WORKS

• In the ICU or the Operating Room …

(Roy, Minor et al. 2007)

EXCEPTIONS• SPONTANEOUS BREATHING

• OPEN CHEST• SIGNIFICANT RHYTHM ISSUES

• RV FAILURE• LOW Vt

WHY

Passive Leg Raise

• MY PATIENTS ARE NOT IN THE OR, ICU, OR EVEN THE HOSPITAL! NOW WHAT?

• Start at 45o semi-recumbent position, then raise the lower limbs to 45o

• Approximately 200-300 mL of blood returned to the central venous compartment

• Transient and reversible “fluid challenge”

(Malbrain and Reuter 2010)

HOW MUCH FLUID

Robert Southey1837

NOT TOO

LITTLE

Miller, Raghunathan, Gan

Best Pract Res ClinAnaesthesiol. 2014 Sep;;28(3):261-­73.

NOT TOO MUCH

Organ function

effects of volume

overload

Outcome benefits of fluid restriction

BOTTOM LINE

FLUIDS ARE DRUGS!

WHAT

– BALANCED CRYSTALLOIDS

• COLLOIDS / ISOTONIC SALINE WHEN INDICATED

WHEN AND HOW MUCH

– GIVE MORE EARLY

• ~30 ML/KG WITHIN 3 HOURS FOR SEVERE SEPSIS

– GIVE LESS LATER

– GIVE NOTHING IF ORAL INTAKE IS GOOD

WHERE CAN I READ MORE

Summary

BALANCE IN ALL THINGS …

THANK YOU FOR YOUR ATTENTION

QUESTIONS???

KR118@DUKE.EDU