Principles of intravenous fluid therapy Jonathan Paddle Consultant in Intensive Care Medicine Royal Cornwall Hospitals NHS Trust 3 rd September 2007

Principles of intravenous fluid therapy

Jonathan Paddle

Consultant in Intensive Care MedicineRoyal Cornwall Hospitals NHS Trust

3rd September 2007

"On the floor lay a girl of slender make and juvenile height, but with the face of a superannuated hag... The colour of

her countenance was that of lead - a silver blue, ghastly tint; her eyes were sunk deep into sockets, as though they had been driven an inch behind their natural position; her mouth was squared; her features flattened; her eyelids black; her

fingers shrunk, bent, and inky in their hue…

In short, Sir, that face and form I can never forget, were I to live beyond the period of man's natural age."

•Investigated cholera outbreak in Sunderland:

•Noted blood “..has lost a large part of its water content.. and.. a great proportion of its neutral saline ingredients..”, leading to venalisation (“blue, thick and cold”); established that the stools contained the missing elements in proportion

•Therapeutic conclusions:“1. To restore the blood to its natural specific gravity;2. To restore its deficient saline matters…

… by the injection of aqueous fluid into the veins.”

WILLIAM BROOKE O’SHAUGHNESSYEdinburgh graduate, age 22 from Limerick

“She had apparently reached the last moment of her earthly existence and now nothing could injure her... Having inserted a tube into the basilic vein, cautiously, anxiously, I watched the effects; ounce after ounce was injected but no visible change was produced.

Still persevering, I thought she began to breathe less laboriously, soon the sharpened features, the 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; at first small and quick, by degrees it became more distinct, fuller, slower and firmer, and in the short space of half an hour, when six pints had been injected, she expressed in a 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”

Thomas A Latta, Leith Physician. Lancet June 18th 1832

“.. But I had not been long gone, ere the vomiting and purging recurring, soon reduced her to her former state of disability … and she sunk in five and a

half hours after I had left her…

…I have no doubt, the case would have issued in complete reaction, had the remedy, which had already produced such effect, been repeated.”

Two to three drachms of muriate of soda (NaCl), two scruples of the bicarbonate of soda in six pints of water and

injected it at temperature 112 Fah

( approx 58mmol/l Na, 49 mmol/l Cl, 9 mmol/l bicarbonate)

Ten of the first fifteen patients died

Dr Latta’s Saline solution

The present day…

Current controversies in fluid therapy

• How much fluid to give

• Which fluid to use

Assessment of volume status

Look at the patient:– Pulse– Blood pressure– Capillary refill– Mucous membranes– Peripheral circulation– Thirst


Try a more invasive approach:

• Urine output

• Arterial line

• Central venous line

• PA catheter

• Oesophageal doppler


How about blood tests?

• U&Es

• Haematocrit

• Plasma/urine osmolality

• Arterial blood gases

• Lactate


OK, so the patient needs fluid…

How much should we give?

Trauma

• 598 adults with penetrating torso injuries

• Randomised to standard care or no fluids until time of operation

Bickell WH et al. Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Torso Injuries. NEJM 1994; 331: 1105-9

50%

55%

60%

65%

70%

75%

Standard Restrictive

Mortality

P=0.04

Trauma

• Cochrane Database of Systematic reviews

• Six randomised controlled studies

• No evidence in support or against early aggressive fluid resuscitation

• 52 animal trials hypotensive resuscitation reduced risk of death

Peri-operative

• 138 patients undergoing major elective abdominal surgery

• Randomised to one of three groups (one control and two goal directed therapy groups

Wilson J et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ 1999; 318: 1099-103

Peri-operative

• Goal-directed therapy was aimed at optimising oxygen delivery to tissues with:– Fluids– Inotropes

• Guided by invasive PA catheter monitoring


Extra 1500 ml fluids pre-op

Peri-operative


However…• RCT 172 patients undergoing elective colorectal

resection• Restrictive fluid regime (to maintain neutral body

weight) vs. standard post-op fluids

Brandstrup B et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003; 238(5): 641-8.

Complications: 33% versus 51% (P = 0.013)

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich,

M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group

Volume 345: 1368-1377 November 8, 2001

Sepsis and the critically ill

Rivers E et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. NEJM 2001; 345: 1368-77

Sepsis and the critically ill

•263 patients presenting with severe sepsis

•Single-centre: large American Emergency department

•Randomised to standard therapy or goal-directed therapy

Protocol group

Treatment given0-6 hours 7-72 hours 0-72 hours

Fluids (ml)

EGDT 4991 8625 13443

Standard 3499 10602 13358

P value <0.001 0.01 0.73

RBC transfusion (%)

EGDT 64.1 11.1 68.4

Standard 18.5 32.8 44.5

P value <0.001 <0.001 <0.001

Vasopressor use (%)

EGDT 27.4 29.1 36.8

Standard 30.3 42.9 51.3

P value 0.62 0.03 0.02

Dobutamine use (%)

EGDT 13.7 14.5 15.4

Standard 0.8 8.4 9.2

P value <0.001 0.14 0.15

Mechanical ventilation (%)

EGDT 53.0 2.6 55.6

Standard 53.8 16.8 70.6

P value 0.90 <0.01 0.02

PA Catheter use (%)

EGDT 0 18.0 18.0

Standard 3.4 28.6 31.9

P value 0.12 0.04 0.01

The take-home message!

• Resuscitate with fluids early and aggressively– They won’t get overloaded– They won’t get pulmonary oedema– They will be less likely to need ICU

• Be guided by markers of tissue perfusion– Urine output– Lactate– Consider central venous oxygen saturations

FACTT Study

• Comparison of two fluid management strategies in acute lung injury

• Randomised controlled trial• 1001 patients with ARDS or ALI• Conservative v liberal fluid therapy• Also compared PAC or CVC• Mortality at 60 days, vent free days, organ failure

free days

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Wiedemann HP, Wheeler AP,

Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-2575

FACTT

• Fluid restriction 43 hrs post admission

• 24 hours post ALI/ARDS

• Renal failure pts excluded

• Volume replete patients



FACTT

• No significant difference in mortality• Restrictive fluid group had:

– Better oxygenation indexes– More ventilator free days– Less renal failure in conservative group

• Recommendations: Conservative fluid approach without PAC

• But…………..



FACTT

• Increase in cardiovascular failure days in patients in conservative group

• Caution in fluid depleted patients.

• Relative young age of patients

• ? Realistic study population



Now for which fluid…Now for which fluid…

What is the choice?

Crystalloids Colloids

Saline Albumin

Dextrose Gelatins

Hartmann’s Starches

Fluid distribution

Capillary wallCell membrane

Roberts I, Alderson P, Bunn F, P Chinnock, K Ker and Schierhout G.

Colloids versus crystalloids for fluid resuscitation in critically ill patients

(Cochrane Review).

The Cochrane Library, Issue 4, August 24th, 2004

Practical differences

Albumin vs. crystalloid

HES vs. crystalloid

Gelatin vs. crystalloid

Dextran vs. crystalloid

“There is no evidence from randomised controlled trials that resuscitation with colloids reduces the risk of death compared to crystalloids in patients with trauma, burns and following surgery.

As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patient types can be justified outside the context of randomised controlled trials”

A Comparison of Albumin and Saline for Fluid Resuscitation in

the Intensive Care Unit

The SAFE Study Investigators

2004; 350: 2247-2256

Study design

• 16 centres in Australia and New Zealand

• Randomised, double-blind, trial of 4% albumin compared to 0.9% Saline for fluid resuscitation in the ICU

• Study fluid given until death, discharge or 28 days

Study design

• 6997 Patients enrolled

• 90% power to detect 3% difference in mortality from baseline of 15% mortality

• A priori sub-groups identified:– Trauma– Severe Sepsis– ARDS

Total administered study fluid

Albumin Saline Ratio

2247 ml 3096 ml 1 : 1.4

Fluids administered and effect

Outcome

ALBUMIN SALINERelative risk

(95% CI)Absolute diff

(95% CI)P value

28 day mortality

726/3473 (20.9%)

729/3460 (21.1%)

0.99

(0.91 to 1.09)0.87

ICU LOS (days)

6.5 ± 6.6 6.2 ± 6.20.24

(-0.06 to 0.54)0.44

Hospital LOS (days)

15.3 ± 9.6 15.6 ± 9.6-0.24

(-0.70 to 0.21)0.30

Duration of mech. Vent.

4.5 ± 6.1 4.3 ± 5.70.19

(-0.08 to 0.47)0.74

Duration of RRT

0.48 ± 2.28 0.39 ± 2.00.09

(-0.0 to 0.19)0.41

Outcome

Subgroup Outcome: 28 day mortality

ALBUMIN SALINERelative risk

(95% CI)P value

Trauma81/596

(13.6%)

59/590

(10.0%)

1.36

(0.99 to 1.86)0.06

Severe Sepsis185/603

(30.7%)

217/615

(35.3%)

0.87

(0.74 to 1.02)0.09

ARDS24/61

(39.3%)

28/66

(42.4%)

0.93

(0.61 to 1.41)0.72

What about starches?

• Starches are polymers of glucose

• α1,6 linkages produce branched chains called amylopectins

• Hydroxyethyl radicals can be substituted on glucose units, hence

HYDROXYETHYL STARCH

Why might they be useful?

• Large molecules, so retained in the plasma

• Stable molecules, so have a sustained effect

• Some evidence of specific anti-inflammatory properties that may be therapeutic

Endothelial properties

• Prospective RCT, single centre• 66 patients >65 years old• Major abdominal surgery

– Ringer’s lactate (n=22)– Normal saline (n=22)– HES 130/0.4 (n=22)

• From induction of anaesthesia until 1st post-op day to keep CVP 8-12mmHg

Boldt J. Int Care Med 2004; 30: 416-22

Endothelial properties

Boldt J. Int Care Med 2004; 30: 416-22

Why might they be bad?

• Potential risk of anaphylaxis

• Some starch solutions cause coagulation disorders

• Risk of renal impairment

• Known incidence of pruritis

Incidence of anaphylaxis

• French multicentre study

• 49 hospitals• 19593 patients• Overall 1 in 456 had

an anaphylactoid reaction

0.00

0.10

0.20

0.30

0.40

0.50

Gelatin Dextran Albumin Starch

%a

ge

of

an

ap

hyl

act

oid

re

act

ion

s

Laxenaire MC. Ann Fr Anesth Reanim 1994; 13: 301-10

Coagulation disorders

Boldt J et al. Br J Anaesth 2002; 89: 722-8

0

500

1000

1500

2000

Post op 5 hr 1st day 2 day (tot)

RL HES 140/0.4 Hextend

**

**

•Small RCT, 21 patients per group

•Major abdominal surgery for malignancy

•Compared blood transfusion requirements according to fluid given

Renal Impairment

• 129 patients in three centres

• Severe sepsis / septic shock

• 6%HES 200/0.6 vs. 3% Gelatin

• Prospective RCT

Schortgen F, Lacherade J-C, Bruneel F et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis:

a multicentre randomised study. Lancet 2001; 357: 911-6

Renal Impairment

Schortgen F et al. Lancet 2001; 357: 911-6

OR 2.57 (1.13 – 5.83) P=0.026

Renal Impairment

• 40 patients, single centre

• HES 130/0.4 vs. Gelatin

• Prospective RCT

Boldt J, Brenner T, Lehmann A et al. Influence of two different volume replacement regimens on renal function in elderly patients undergoing cardiac surgery: comparison of a new

starch preparation with gelatin. Int Care Med 2003; 29: 763-9

Renal Impairment

Boldt J et al. Int Care Med 2003; 29: 763-9

No significant differences

Pruritis

• 85 consecutive cardiac patients• Structured interview• 58 received EloHAES• 27 received no HES

Morgan PW and Berridge JC. Giving long-persistent starch as volume replacement can cause pruritis after cardiac surgery.

Br J Anaesth 2000; 85: 696-9.

Pruritis

• Pruritis experienced in:– 13 (22%) of EloHAES patients– 0 (0%) of non-HES patients (P=0.007)

• Median onset (range) 4 (1-12) weeks• Greatest duration >9 months

Morgan PW and Berridge JC. Giving long-persistent starch as volume replacement can cause pruritis after cardiac surgery.

Br J Anaesth 2000; 85: 696-9.

Time to put it all together!

How much fluid

• Trauma– Restrictive fluid strategy until bleeding

controlled

• Peri-operative– Fluids early (?pre-op), then cut back

• Sepsis– Early aggressive fluids to restore perfusion– Restrict fluids late to avoid oedema

Which fluid

• It probably doesn’t matter!

• Avoid dextrose (water) as large volumes will be required, worsening tissue oedema

• If using crystalloid, the patient will require 1.4 times the volume compared to colloid

• Crystalloid may be better in trauma

• Colloid (or possibly starches) may be better in critically ill / sepsis

Documents

Principles of intravenous fluid therapy Jonathan Paddle Consultant in Intensive Care Medicine Royal Cornwall Hospitals NHS Trust 3 rd September 2007