Fluid Resuscitation

The relation between the flow in a long narrow tube, the viscosity of the fluid, and the radius of the tube is expressed mathematically in the Poiseuille–Hagen formula:

where

Since flow is equal to pressure difference divided by resistance (R),

Since flow varies directly and resistance inversely with the fourth power of the radius, blood flow and resistance in vivo are markedly affected by small changes in the caliber of the vessels. Thus, for example, flow through a vessel is doubled by an increase of only 19% in its radius; and when the radius is doubled, resistance is reduced to 6% of its previous value. This is why organ blood flow is so effectively regulated by small changes in the caliber of the arterioles and why variations in arteriolar diameter have such a pronounced effect on systemic arterial pressure.

How it works:
Poiseulle's law states that the flow rate Q is also dependant upon fluid viscosity η, pipe length L and the pressure difference between the ends P by

but all these factors are kept constant for this demo so that the effect of radius is clear.

The apparatus consists of two 12 liter Plexiglass tanks, one to be emptied through a single 6mm bore capillary tube and the other through sixteen 3mm bore tubes. All tubes are 60cm in length. For direct comparison, all tubes need to be opened to the tanks simultaneously and this is achieved using a valve consisting of a long steel rod with 17 holes drilled through it, corresponding to the 17 tubes (figure 1b). The rod runs the length of the tanks and has a handle that rotates it to align the holes in the rod with those in the tank.

figure 1a. Poiseulles's apparatus, and 1b. detail of valve.

Elmhurst Equipment

Choice of colloid:

agents differ by half-life, mw, colloid oncotic pressure, side effects, and cost; albumin small molecule at 69,000 daltons (d); Hespan—much larger (450,000 d) than albumin; has anticoagulant effect (lowers factor VIII and von Willebrand’s factor); dosage limited to 20 mL/kg per day; however, since large- mw molecules persist in circulation, speaker recommends 20-mL/kg total dose; most studies conclude Hespan increases risk of bleeding in risk-prone surgical procedures; Hextend similar to Hespan, but in balanced salt solution rather than normal saline; several studies suggest lower risk for coagulopathy with Hextend; trial that randomized patients to receive Hextend or standard hetastarch solution found both equally efficacious in treating hypovolemia; patients received >1.5 L on average; almost two fifths of patients received >20 mL/kg; coagulopathy found only in hetastarch group; trend toward lower bleeding, red blood cell, and platelet transfusions among Hextend patients; new medium-weight starches—under study; not associated with coagulopathy, even in large doses; they may reduce permeability of blood vessels by plugging holes; animal studies suggest they also decrease inflammation, neutrophil activation, ischemia-reperfusion injury, and improve microcirculatory flow; hypertonic saline— greater than or equal to 3% saline solution given primarily in prehospital phase to draw water out of cells and interstitium; each mL given causes 3-mL increase in circulating blood volume; decreases extravascular fluid, cerebral edema, and intracranial pressure; may improve myocardial contractility, microcirculatory flow, and decrease inflammation; one meta-analysis showed it was not effective alone, but somewhat beneficial in combination with dextran

Colloids
Acacia and albumin: in World War I, combat casualties resuscitated with acacia gum colloid until plasma introduced; in 1940s, “no-salt theory” in vogue; during World War II, albumin separated from plasma and became popular resuscitative fluid; German military used colloid named Periston (povidone; osmotically active, high molecular-weight derivative of vinyl; found to accumulate in spleen and reticuloendothelial system [RES] of animals)
Hetastarch (eg, Hespan, Hextend): “just a saline solution with a little bit of cornstarch added to it”; United States military Tactical Combat Casualty Care (TCCC) specifies 1 L of Hespan for fluid resuscitation; speaker’s institution (large naval hospital) stocks only Hextend
Gelatins/Haemaccel (polygeline): only colloid available to speaker in Australia; unavailable in United States since 1978 because of high incidence of hypersensitivity reactions to gelatin
Blood substitute prospects (intravascular O2 carriers)
Perflurochemical (PFC) technology: Oxygent (perflubron) one example; pure PFCs not miscible with water; carry significantly more O2 than H2 O
Hemoglobin-based O2 carriers: Oxyglobin (hemoglobin glutamer-200) approved by Food and Drug Administration (FDA) in 1998 for veterinary use; not approved for use in humans

Use albumin in SBP (Sort P, Navasa M, Arroyo V, et al: Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341:403–409)

Colloids vs. Crystalloids

A comparison of albumin and saline for fluid resuscitation in the intensive care unit.
N Engl J Med 2004 May 27;350(22):2247-56 (ISSN: 1533-4406)

Finfer S; Bellomo R; Boyce N; French J; Myburgh J; Norton R
ANZICS CTG, Level 3, 10 Ievers St., Carlton, VIC 3053, Australia. ctg@anzics.com.au; Collective Name: SAFE Study Investigators.

BACKGROUND: It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. METHODS: We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization. RESULTS: Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (+/-SD) numbers of days spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6, respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/-2.0, respectively; P=0.41). CONCLUSIONS: In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. [Copyright 2004 Massachusetts

Colloids vs. Crystalloids
A comparison of albumin and saline for fluid resuscitation in the intensive care unit.

N Engl J Med 2004 May 27;350(22):2247-56 (ISSN: 1533-4406)

Finfer S; Bellomo R; Boyce N; French J; Myburgh J; Norton R
ANZICS CTG, Level 3, 10 Ievers St., Carlton, VIC 3053, Australia. ctg@anzics.com.au; Collective Name: SAFE Study Investigators.

BACKGROUND: It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. METHODS: We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization. RESULTS: Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (+/-SD) numbers of days spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6, respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/-2.0, respectively; P=0.41). CONCLUSIONS: In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. [Copyright 2004 Massachusetts

Fluid
Na
Cl
K
Ca
Mg
Buffer
pH
Osm
Plasma
141
103
4-5
5
2
Bicarb
7.4
289
.9% NaCl
154
154

5.7
308
7.5% NaCl
1283
1283

5.7
2567
Ringer's
130
109
4
3

Lactate
6.4
273
Normosol
140
98
5

3
Acetate
7.4
295
Plasma-Lyte
140
98
5

3
Gluconate
7.4
295

5% dextrose has 170 kCal per liter

Authors
Than N. Shah N. White J. Lee JA. Orchard CH.

Institution
Department of Physiology, University of Leeds, United Kingdom.

Albumin vs. Saline

Follow-up analysis looked at whether folks with low baseline albumin got more benefit from albumin--they didn't (BMJ 20006;333(7577):1044)

Further analysis shows albumin when given at same volume leads to more hyperchloremic acidosis; however, this difference is minor. amount of fluid is stronger predictor. (Crit Care Med 2006;34(12):2891)

Kidding, these colloids are great for avoiding blood
loss, but bad for people already with too much
chloride inside their veins...Voluven has 900 mg
chloride per 100 ml. So when I recommend it I am
sacrificing acid base balance a bit for the sake of
the bleeding tendencies...
I would not recommend Hextend and other high MW
colloids as a first choice only because she is old,
her platelets can be a little tricky (if she is
hypertensive and diabetic good chance someone gave her
a bit of aspirin less than three weeks ago, uh?), and
high molecular weight, slowly degradable starches have
a greater impact on coagulation, detectable by TEG, it
can cause the patient to bleed more especially those
with bad platelets or low fibrinogen levels. Otherwise,
Hextend is one of the colloids with lowest Cl-
concentration (124mEq/L), against HESpan and Pentaspan
both with a high Cl- content(154mEq/L).If her
acidosis is lactic, then HESpan or Pentaspan would be
OK, bec they do not have lactate in their formula, as
Hextend does (28 mEqs/L of L-lactate)

Big world of caution:

You will recall that in SAFE (New Engl J Med 2004, 350:2247-2256) the a priori trauma subgroup (17.3% of 7000 patients, making it the biggest ever trauma fluid study) showed evidence of harm when albumin was given to trauma patients. On subgroup analysis this harm appeared to be restricted to those with a traumatic brain injury. A 2 year followup of these TBI patients has been analysed and is about to be published and you should all look very closely at the results (I can't say more until it hits the press).

The other big message from SAFE is that the 3:1 colloid to crystalloid ratio that we are taught in books (which comes from healthy volunteer dogs in the 1950s) is utter rubbish when applied to sick humans. In every subgroup there was a consistent 1.4:1 ratio (volume of albumin conpared to volume of saline, to acheive a clinical resuscitation endpoint). This will creep into the books eventually.

For now I think it is fair to say that anyone who gives colloids to a trauma patient in ICU is being very unwise!

catheter length does not change flow rate in vitro (as opposed to purely mathematical) (Injury 2006;37(1):41)

Hypertonic Saline

Powers KA, Zurawska J, Szazi K, et al. Hypertonic resuscitation of

hemorrhagic shock prevents alveolar macrophage activation by preventing

systemic oxidative stress due to gut ischemia/reperfusion. Surgery

2005;137:66-74.

The problem of reperfusion injury after ischemia has remained central

in many fields, ranging from stroke and MI to resuscitation from shock to

transplantation, and considerable progress in unraveling the cellular and

molecular events occurring during reperfusion has been made in the past

2 decades. Briefly, ischemia leads to generation of reactive oxygen species,

which then activate various nuclear transcription factors in macrophages

and neutrophils, leading to production and release of inflammatory

mediators. During conditions of global ischemia (shock), the intestinal

mucosa is a, if not the, primary source of these inflammatory mediators.

Hypertonic saline appears to have more beneficial effects other than just

allowing smaller volumes of resuscitation fluid and, thus, decreasing

edema. It has direct vasodilating properties and prevents capillary

narrowing, reducing microcirculatory dysfunction and, thereby, reducing

oxidant stress and the consequent production of inflammatory mediators.

The present study is one in a series of studies in rats of hemorrhagic shock.

The authors demonstrated that the use of small-volume hypertonic saline

during resuscitation prevented both gut injury as reflected histologically, as

well as lung leukosequestration and priming of alveolar macrophages.

	mEq/L
	Na	Cl	K	Ca	Mg	Glucose	Buffer	SID	pH	mOsm/L
Plasma	142	103	4	5	2		Bicarb 22-32		7.4	289
Interstitial	140	117	4.5	5	2		Bicarb 28
Intracellular	10	103	150	1	40		Bicarb 7

.9% NaCl	154	154						0	5.7	308
.45% NaCl	77	77						0	5.7	154
3% NaCl	513	513						0		1026
7.5% NaCl	1283	1283						0	5.7	2567
23.4% NaCl	4004	4004						0		8008
NaBicarb	44						Bicarb 44	44

Ringer's	130	109	4	2.7			Lactate 28	28	6.4	273
Normosol-R	140	98	5		3		Acetate 50	50	7.4	295
P-Lyte A	140	98	5		3		Gluconate 23 Acetate 27	50	7.4	295

Hemosol	140	109.5	0	1.75	0.5		Bicarb 32	32

Albumin 5%	140 ±15		<2.5						7.4	330
Albumin 25%	140 ±15									1500
Hespan	154	154					6% Hetastarch		6.5	310
Dextran 40	154	154				250 g/L

Whole Blood (CPD)	156-168		3.9-21						6.8-7.2	HCT 35-40
PRBC (AS-1)	117		?-49						6.6	HCT=59
PRBC (CPD)			?-95						6.6	HCT=77
PRBC (CPDA-1)	111-169		5.1-78						6.7-7.5	HCT 65-80


	Na	Cl	K	Ca	Mg	Glucose	Buffer		pH	mOsm/L

Body Fluids	mEq/L
	Na	K	Cl	Bicarb	L/day
Saliva	30	20	35	15	1-1.5
Gastric, pH<4	60	10	90		2.5
Gastric, pH>4	100	10	100		2
Bile	145	5	110	40	2
Duodenum	140	5	80	50
Pancreas	140	5	75	90	0.7-1
Ileum	130	10	110	30	3.5
Cecum	80	20	50	20
Colon	60	30	40	20
New Ileostomy	130	20	113	20	0.5-2
Adapted Ileostomy	50	5	30	25	0.4
Colostomy	50	10	40	20	0.3