EMCrit.org | Emergency Critical Care

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

Perioperative

2. Use crystal only for insensible and urine output. Insensible=0.5 ml/kg/hr or 1 ml/kg/hr in open abdominal

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.

Streat on Post-op Fluids

ECF (or ECW) is a body compositional term -- being that component of the total body water which is measured by an indicator or component which is found in that space. Conveniently this is sodium (Moores early work with radiosodium -- Na24) or chloride (difficult -- but we came up with a novel method when neutron scanning an oedematous ICU patient on New Years day in 1985 I think it was -- see PDF) or Bromide (the usual modern method).

Interstitial fluid is usually thought of as a fluid that you get from sampling a "blister" or similar -- an anatomic part of the body, not what Moore called "chemical anatomy" when referring to body composition. Similarly, "plasma volume" is the distribution volume of an appropriate indicator -- usually the ten minute distribution volume of a blous of radiolabelled albumin (often Iodine-125). However, plasma (and "interstitial fluid") also contain proteins etc as Prasanna's paper points out.

The "plasma volume" and the "interstitial volume" have "'near enough" the ionic composition of the ECF/ECW -- but their protein "concentrations" vary from each other and also in disease.

In fact, the distribution volume of various substances placed into the bloodstream is different -- water, sodium, proteins and other macromolecules. Water (solute free-water, pure and unadulterated water) distributes across the TBW (the tritium or deuterium or ethanol or antipyrine space -- all close enough to each other for most peoples needs). Sodium distributes across the body compositional entitity the "ECW" (but some of the sodium is located anatomically within cells -- at approximately 10 mmol/l in health, more in certain disease states). Macromolecules (colloids) have varying distribution volumes, depending on their molecular size, the nature of the endothelium, the absolute and relative sizes of the "plasma" and "interstitial fluid" volumes and the proportional physical phase state (sol/gel) of the "interstitium". All of these elements are disturbed in critical illness.

For example -- TBW is increased by 5-20 litres in trauma/sepsis -- see papers -- no matter what you use for circulatory restoration -- but it can be made bigger if you give too much ... Also -- the well-resuscitated patient with vasodilated sepsis has an expanded blood volume, usually around 140% of normal, which is comprised of a much larger plasma volume than normal (and co-existent haemodilution) and the same or only slightly larger red cell mass. The distribution volume of macromolecules is larger in sepsis -- because of the interaction of several factors -- an increase in "leak" (quantifiable by a rapid disappearance of isotope-labelled protein from the plasma), an increase in distribution volume outside the blood ("the interstitium") which is in part size-related (oedema) and in part an increase in the "permeability of the gel phase of the interstitium to macromolecules". This sol/gel integrity issue is different in sepsis from trauma -- sepsis probably involves all of the effects of "capillary leaks" and "disrupted gel phase" and "bigger interstitium".

So ... all resuscitation fluids (those with sodium concentration similar to plasma) distrubute themselves across a distribution space which is larger than the plasma volume into which they are infused. This is not "leak" (like the little Dutch boy with his finger in the dike trying to plug up the hole) but universal physical reality -- an inevitable consequence of chemistry and physics. SAFE showed that (for all-comers at least, not reported separately for sepsis patients) the ratio of "clinically equipotent" colloid and crystalloid was around 1:1.3 -- i.e. you needed 30% more salt water (not 2-3 times as much). Admittedly, the other data showed that "colloid" patients probably had slightly higher blood volumes (higher venous pressures, lower inotrope doses) but that it did not matter (survival).

Its best not to think too hard about "colloid osmotic pressures" "starling forces" "distribution volumes" "capillary leaks" "sol/gel integrity" and the like when prescribing fluids clinically. Think instead of "restoring circulating blood volume", "increasing blood volume (not "venous pressures') in vasodilated states", "give red cells sparingly", "use a SAFE fluid, safely" and "ensure that you don't use resuscitation fluids as maintenance fluids". When resuscitation fluids are not needed any more, give salt-free water (the patients have a store of 700-3000 mmol of sodium on board already you fool) and titrate it to desired serum osmolality. Wait for passive de-salting, or if renal function and circulation can take it -- diurese the patient at this stage. How easy is that?

Answer -- 1ml/kg/hr 5% glucose in water -- assuming adequate volume restoration and stable inotrope dose. Most patients (90% or more) get such a regimen, and thrive on it. Switch to enteral feeding ASAP (start within 24 hours in patients expected to stay longer than 3 days) and reduce 5% dextrose down to 10ml/hr for medication vehicles if needed. Adjust 1ml/kg/hr down sharply (to 10 ml/hr) if controlled mild hyperosmolality required for brain oedema or intracranial hypertension. This will usually lead to serum osmolality of around 295 after 24 hours or so. Use bolus volume only if required for cardiovascular performance enhancement (I use 0.9% saline because it is SAFE and very cheap -- like me). Assessment is clinical, clinical and clinical. Examine the patient, check the peripheral perfusion, HR, MAP, inotrope dose, urine output, oximetry, respiratory compliance ...

Yes, as a guide to the amount of free water -- i.e. free water is titrated to serum osmolality (er, serum sodium if you want it that way). If serum sodium is falling -- cut back the free water -- don't add salt. No, not as a guide to the amount of sodium to give the patient -- that is determined by the circulation and renal function, the extent of oedema or otherwise....

Before you ask or comment -- no, hyponatraemia is not an "inevitable consequence" of this method of fluid therapy. If it occurs it is a sign of excess administered free water -- an iatrogenic complication. Remember, I am at the same time trying to manage the patient with the lowest total body sodium (i.e. lowest degree of ECW expansion) possible at any point in time. This means allowing "passive de-salting" in the post-acute phase (and active frusemide-induced diuresis as well). It means thinking about body composition changes in each phase of the illness -- and not just electrolyte concentrations. Yes, I do resuscitate patients from shock with lots of volume, especially septic shock patients. But when shock is reversed -- time to stop that salt and cut back that water and let homeostasis do its thing ...

Leo, I was very much an Inotrope guy when I trained (My Boss was a ;lover of Inotropes but then we had very few - virtually Dopamine and Adrenaline).
I am now less into Inotorpes and more into volume but aggressively restrict fluids after 12 hours post open heart (after the theoretical low ouput window). With this policy, i am able to fast track patients out of the ICU and hiome earlier. having said that my standard weaning polcy is 3 mics dopamine (Godforbid I will be killed by Stephen Streat and the ANZICS crowd) + 3 mics dobutamine and Adlib Nitroprusside. Milrinone is selecitvley used in patients with RV dysfunction, RVOT resection and pulmonary hypertension to prempt the pathophysiologuical dip in CO at 8 hours after surgery.I fill and dilate them as required in the first few hours till they are warm and toasty. After that there is vigorous volume restriction and diuresis and switching off of all inotropes (basiocally once they are warm and toasty). With this protocol I send patients home (Home can mean 500 kms away) generally after 72 hours after repairs etc.Plain Inotrope strategy with volume restriction does not allow this 9tried it and failed)
Prasanna

	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

Isolyte S	140	98	5		3		Acetate 27/ Gluconate 23
	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