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SHOCK & RESUSCITATION

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the ICU typically proceeds from a more controlled baseline.

As in any emergent situation, the priorities of airway, breath-

ing, and circulation must be addressed sequentially.

Although many ICU patients will already have an established

airway, attention to this area of concern is always the first pri-

ority. Techniques to control the airway and reestablish ade-

quate breathing are discussed in Chapter 11.

Intravenous access through at least two large-bore

(16-gauge) catheters is mandatory. The relatively small

ports on pulmonary artery and triple-lumen catheters are

inadequate for rapid fluid resuscitation and should be used

only until larger catheters can be placed. Central venous

catheters inserted in the internal jugular or subclavian vein

generally should not be inserted in hypovolemic patients

for emergent resuscitation because of the risk of a pneumoth-

orax associated with attempts to place a cather into a col-

lapsed overlying vein.A quick search should be made for

sources of blood and fluid loss. Potential sources include gas-

trointestinal bleeding, accelerated fluid loss through fistulas,

disconnection of intravenous access lines with retrograde

bleeding, and disruption of vascular suture lines. When exter-

nal bleeding is present, direct pressure over the site should be

applied until definitive surgical control can be secured. Blind

probing of a bleeding wound with clamps almost invariably

fails to control the bleeding and may cause further injury.

B. Fluid Resuscitation—Rapid fluid resuscitation is the cor-

nerstone of therapy for hypovolemic shock. Fluid should be

infused at a rate sufficient to rapidly correct the deficit. In

younger patients, infusion is typically at the maximum rate

sustainable by the delivery equipment and the access vein. In

older patients or those with prior cardiac disease, infusion

should be slowed once a response is detected to prevent com-

plications associated with hypervolemia.

Parenteral solutions for the intravenous resuscitation of

hypovolemic shock generally are classified as crystalloids or

colloids depending on the highest molecular weight of the

species they contain.

1. Crystalloids—Crystalloid solutions have no species with

a molecular weight greater than 6000. Although a large num-

ber of crystalloids are available, only those isotonic with

human plasma that have sodium as their principal osmoti-

cally active particle should be used for resuscitation.

Commonly available solutions are listed in Table 11–3.

Because they have low viscosity, crystalloids can be adminis-

tered rapidly through peripheral veins.

Because isotonic fluids have the same osmolality as

body fluids, there are no net osmotic forces tending to

move water into or out of the intracellular compartment.

Therefore, the electrolytes and water partition themselves

in a manner similar to the body’s extracellular water con-

tent: 75% extravascular and 25% intravascular. When iso-

tonic crystalloids are used for resuscitation, administration

of approximately three to four times the vascular deficit is

required to account for the distribution between the intra-

and extravascular spaces. This partitioning typically occurs

within 30 minutes after the fluid is given. Within 2 hours,

less than 20% of the infused fluid remains within the

intravascular space.

Cardiogenic

Shock

Cardiac

Compressive

Shock

Hypovolemic or Traumatic Shock

Mild Moderate Severe

Low-Output

Septic Shock

High-Output

Septic Shock

Neurogenic

Shock

Skin perfusion Pale Pale Pale Pale Pale Pale Pink Pink

Urine output Low Low Normal Low Low Low Low Low

Pulse rate High High Normal Normal High High High Low

Mental status Anxious Anxious Normal Thirsty Anxious Anxious Anxious Anxious

Neck veins Distended Distended Flat Flat Flat Flat Flat Flat

Oxygen consumption Low Low Low Low Low Low Low Low

Cardiac index Low Low Low Low Low Low High Low

Cardiac filling pressures High High Low Low Low Low Low Low

Systemic vascular

resistance

High High High High High High Low Low

From Holcroft J, Robinson MK: Shock: Identification and management of shock states. In: Care of the Surgical Patient. Scientific

American, 1992.

Table 11–2. Clinical findings associated with shock.

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228

Crystalloid solutions are safe and effective for resuscita-

tion of patients in hypovolemic shock. The major complica-

tions associated with their use are undertreatment and

overtreatment. Clinical parameters such as restoration of

urine output, decreased heart rate, and increased blood pres-

sure should be used to determine when a sufficient quantity

of fluid has been given. Restoration of mental status, skin

turgor, and capillary refill are also useful parameters. Central

venous or pulmonary artery pressure monitoring is useful in

patients with preexisting cardiopulmonary disease.

Excessive administration of crystalloids is associated with

generalized edema. Unless quantities sufficient to increase the

pulmonary hydrostatic pressure to very high levels are given

(typically >25–30 mm Hg), pulmonary edema does not occur.

Subcutaneous edema may be a significant problem because it

limits patient mobility, increases the potential for decubitus

ulcers, and potentially restricts respiratory excursions.

It has been shown recently that the type of crystalloid used

may exert an important effect on the cellular injury caused by

hemorrhagic shock. Investigation of this “resuscitation injury”

has shown that the

-isomer found in traditional lactated

Ringer’s solution (a racemic mixture along with the

-isomer)

may have adverse immunoinflammatory properties.

Additional work has shown that both pulmonary and hepatic

apoptosis may be reduced if lactate in the solution is

replaced with either sodium pyruvate, ethylpyruvate, or β-

hydroxybutyrate. It is believed that the modified Ringer’s

solutions exert their protective effect through posttranslational

modification of important regulatory proteins and by selective

acetylation of histones. Presently, however, the choice of the

specific crystalloid for resuscitation remains largely a matter

of individual preference. Normal saline has the advantages of

being universally available and being the only crystalloid that

can be mixed with blood. Because its chloride concentration is

significantly higher than that of plasma, patients resuscitated

with normal saline often develop a fixed hyperchloremic

metabolic acidosis that requires renal chloride excretion for

correction. Lactated Ringer’s solution has the advantage of a

more physiologic electrolyte composition. The added lactate is

converted to bicarbonate in the liver. Such conversion occurs

readily in all but the sickest of patients.

Hypertonic saline solutions are crystalloids that contain

sodium in supraphysiologic concentrations. They expand the

extracellular space by exerting an osmotic effect that dis-

places water from the intracellular compartment. They also

may exert a mild positive inotropic effect as well as produc-

ing systemic and pulmonary vasodilation. In comparison

with isotonic crystalloids, hypertonic saline decreases wound

and peripheral edema. Recent studies have indicated, how-

ever, that hypertonic saline resuscitation may increase the

incidence of bleeding. Animal models indicate that this may

be due to decreased ADP-mediated platelet aggregation.

Hypertonic saline solutions have received recent attention,

particularly with regard to resuscitation of battlefield casualties,

Solutions fluid

Glucose

(g/L)

–

HCO

–

HPO

–

(meq/L

)

Extracellular fluid 1000 140 102 27 4.2 5 3 3 0.3

5% dextrose and water 50

10% dextrose and water 100

0.9% sodium chloride

(normal saline)

154 154

0.45% sodium chloride

(0.5 normal saline)

77 77

0.21% sodium chloride

(0.25 normal saline)

34 34

3% sodium chloride

(hypertonic saline)

513 513

Lactated Ringer’s solution 130 109 28

∗

4 2.7

0.9% ammonium chloride 168 168

From Miller TA, Duke JH: Fluid and electrolyte management. In: Manual of Preoperative and Postoperative Care. Dudrick SJ et al (editors).

Saunders, 1983.

∗

Present in solution as lactate but is metabolized to bicarbonate.

Table 11–3. Composition of balanced salt solutions.

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SHOCK & RESUSCITATION

229

because small volumes may produce large effects.

Additionally, hypertonic saline may suppress neutrophil func-

tion through the modulation of chemoattractant receptor sig-

naling pathways. Recent clinical work has found no increase

in the incidence of hypernatremic seizures, increased bleeding

or blood transfusion requirement, coagulopathies, renal fail-

ure, cardiac arrhythmias, or central pontine myelinosis.

Hypertonic saline also has been shown to be advantageous

when mixed with artificial colloids such as dextran.

2. Colloids—As a group, colloids are solutions that rely on

high-molecular-weight species for their osmotic effect.

Because the barrier between the intra- and extravascular

spaces is only partially permeable to the passage of these

molecules, colloids tend to remain in the intravascular space

for longer periods than do crystalloids. Smaller quantities of

colloids are required to restore circulating blood volume.

Because of their oncotic pressure, colloids tend to draw fluid

from the extravascular to the intravascular space. They are

significantly more expensive to use than crystalloids, even

though smaller absolute volumes are required. The use of

albumin solutions in the initial resuscitation stages of hypo-

volemic shock has not been shown to be more effective than

the use of crystalloid. Rather, a meta-analysis of 26 prospec-

tive, randomized trials found an increased absolute risk for

death of 4% when colloids were used for resuscitation.

a. Albumin—Albumin (normal serum albumin) is the

most commonly used colloid. It has a molecular weight of

66,000–69,000 and is available as a 5% or 25% solution.

Normal serum albumin is approximately 96% albumin,

whereas plasma protein fraction is 83% albumin. Each gram

of albumin can hold 18 mL of fluid in the intravascular

space. The serum half-life of exogenous albumin is less than

8 hours although less than 10% leaves the vascular space

within 2 hours after administration. When 25% albumin is

administered, it results in increased intravascular volume

approaching five times the administered quantity.

Like crystalloid infusion, the endpoints for the adminis-

tration of colloid to patients in hypovolemic shock are

largely subjective. Because albumin has been implicated as a

cause of decreased pulmonary function, strict attention to

resuscitation endpoints is required. Other reported compli-

cations include depressed myocardial function, decreased

serum calcium concentration, and coagulation abnormali-

ties. The latter two may be due simply to volume effects.

b. Hetastarch—Hetastarch (hydroxyethyl starch) is a syn-

thetic product available as a 6% solution dissolved in normal

saline. It has an average molecular weight of 69,000. Forty-six

percent of an administered dose is excreted by the kidneys

within 2 days, and 64% is eliminated within 8 days. Detectable

starch concentrations may be found 42 days after infusion.

Hetastarch is an effective volume expander, with effects that

typically last between 3 and 24 hours. Intravascular volume

increases by more than the volume infused. Most patients

respond to between 500 and 1000 mL. Renal, hepatic, and

pulmonary complications may occur when dosing exceeds

20 mL/kg per day.

Hetastarch may cause a decreased platelet count and pro-

longation of the partial thromboplastin time owing to its

anti–factor VIII effect. Anaphylaxis is rare. A combination

product containing 6% hetastarch in a balanced salt solution

is now available. Because it may cause inhibition of factor

VIII, its use for large-volume resuscitation requires further

review. When used, it is typically administered at doses of

500–1000 mL.

A similar five-carbon preparation (pentastarch) is cur-

rently available only for leukapheresis but is also a useful vol-

ume expander. It may have fewer effects on the coagulation

cascade than does hetastarch.

c. Dextrans—Two forms of dextran are generally available:

dextran 70 (90% of molecules have MW 25,000–125,000) and

dextran 40 (90% of molecules have MW 10,000–80,000). Both

may be used as volume expanders. The extent and duration of

expansion are related to the type of dextran used, the quantity

infused, the rate of administration, and the rate of clearance

from the plasma. The lower-molecular-weight molecules are

filtered by the kidney and produce diuresis; the heavier ones

are metabolized to CO

and water. The higher-molecular-

weight dextrans remain in the intravascular space longer than

do the lighter compounds. Dextran 70 is preferred for volume

expansion because it has a half-life of several days. A 10% solu-

tion of dextran 40 has a greater colloid oncotic pressure than

the 70% solution but is cleared from the plasma rapidly.

Several complications are associated with dextran admin-

istration, including renal failure, anaphylaxis, and bleeding.

Dextran 40 is filtered by the kidney and may result in an

osmotic diuresis that actually decreases plasma volume. It

should be avoided in patients with known renal dysfunction.

Dextran 70 infrequently has been associated with renal fail-

ure. Anaphylactic reactions occur in patients with high

anti–dextran antibody titers. The incidence of reactions is

between 0.03% and 5%.

Both dextrans inhibit platelet adhesion and aggregation

probably via factor VIIIR:ag activity. The clinical effect is simi-

lar to von Willebrand’s disease. The effect is greater with dex-

tran 70 than with dextran 40. Both preparations may interfere

with serum glucose determinations and blood cross-matching.

d. Other colloids—Modified fluid gelatin (MFG) and

urea-bridged gelatins are prepared as 3.5% and 4% solutions

in normal saline, respectively. Both are effective plasma vol-

ume expanders. Their low molecular weight leads to rapid

renal excretion. Anaphylactoid reactions (0.15%) are the

most common complication. Rapid infusion of the urea-

bridged formulation causes histamine release from mast cells

and basophils. The incidence of allergic reactions is less for

MFG. Gelatins may cause depression of serum fibronectin.

They are not associated with renal failure and do not inter-

fere with blood banking techniques. These preparations are

used widely in Europe and in the military for mass casualties.

They are currently unavailable in the United States.

Oxygen-carrying solutions such as stroma-free hemoglo-

bin and perfluorocarbons are the subjects of active research.

At present, however, they are available only for limited use

and in clinical trials.

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230

3. Blood—The hemoglobin concentration at which blood

should be transfused is still hotly debated. The so-called trans-

fusion trigger depends on a number of factors, including age,

comorbid factors, presence of ongoing bleeding, etc. In healthy

human volunteers, isovolemic hemodilution is tolerated at

concentrations as low as 5 g/dL, whereas the National

Institutes of Health recommend a concentration of greater

than 7 g/dL. Traditionally, the transfusion trigger was set at

10 g/dL, but epidemiologic studies have shown that early

transfusion is a strong independent risk factor for multiple-

organ failure. While the exact mechanism is not known, neu-

trophil priming may play a role. This occurs when passenger

leukocytes accompanying stored red blood cells generate proin-

flammatory agents. Such agents increase at between 14 and 42

days of blood storage. Additional factors such as decreased red

cell deformability and cytokine production also have been cited.

Current Controversies and Unresolved Issues

A. Crystalloids versus Colloids—The crystalloid versus col-

loid debate has emerged anew, fueled by the findings that the

traditional lactated Ringer’s solution may be proinflamma-

tory and that hypertonic saline may suppress disadvanta-

geous immune responses. Presently, there is no clear

indication that the current use of lactated Ringer’s or normal

saline as the resuscitation fluid of choice should be changed.

Additional studies on the use of single-isomer solutions and

hypertonic saline will be required. A meta-analysis of colloid

use found an increase in the absolute number of deaths when

compared with crystalloid, thus discouraging the use of

high-molecular-weight solutions.

B. Ischemia-Reperfusion—Ischemia-reperfusion is an area

of critical investigation. Clarification of the mechanism of

oxygen radical tissue destruction with tissue reperfusion may

help to prevent some of the complications of ischemia. A

number of compounds, including diltiazem, amiloride, and

pentoxifylline, have been explored in an effort to improve car-

diac, peripheral vascular, and renal function after reperfusion.

C. Endpoints—The endpoints of resuscitation are parame-

ters such as blood pressure, heart rate, and urine output.

Tissue-specific monitors such as tissue oxygen tension

(TP

) and intramucosal pH (pH

) have received recent

attention as objective indices. Because of the time required

for pHi sample collection, it is unlikely to become a clinically

useful tool for resuscitation. It may, however, be valuable for

monitoring patients after they have stabilized. Tissue oxygen

measurements use several modalities, including electrodes

and fluorescence-quenching optodes. The latter has proved

to be a reliable indicator of oxygen tension in the subcutaneous

and visceral tissues during shock and resuscitation. Its clini-

cal usefulness remains to be demonstrated.

D. Bacterial Translocation—The anomalous appearance of

sepsis in patients who develop hypovolemic shock has raised

the question of intestinal bacterial translocation. This theory

proposes that ischemia of the intestinal mucosa allows

luminal bacteria to pass through or between cells and into

the portal venous system. The mechanism has been clearly

demonstrated in animals, but definitive evidence in humans

is lacking. Elucidation of this mechanism may provide infor-

mation on the prevention of sepsis in this setting.

Alam HB, Rhee P: New developments in fluid resuscitation. Surg

Clin North Am 2007;87:55–72. [PMID: 17127123]

Dutton RP: Current concepts in hemorrhagic shock. Anesthesiol

Clin 2007;25:23–34. [PMID: 17400153]

Gutierrez G, Reines HD, Wulg-Gutierrez ME: Clinical review.

Hemorrhagic Shock 2004;8:373–81.

Holcroft JW, Robinson MK: Shock: Identification and manage-

ment of shock states. In: Care of the Surgical Patient. Scientific

American, 1992.

Moore FA, McKinley BA, Moore E: The next generation in shock

resuscitation. Lancet 2004;363:1988–96. [PMID: 15194260]

Moore FA et al: III Guidelines for shock resuscitation. J Trauma

2006;61:82–9. [PMID: 16832253]

Martinez-Mier G, Toledo-Pereyra LH, Ward PA: Adhesion mole-

cules and hemorrhagic shock. J Trauma 2001;51:408–15.

[PMID: 11493811]

Vercueil A, Grocott MPW, Mythen MG: Physiology, pharmacology,

and rationale for colloid administration for the maintenance of

effective hemodynamic stability in critically ill patients.

Transfusion Med Rev 2005;19:93–109.

Wang P et al: Diltiazem restores cardiac output and improves renal

function after hemorrhagic shock and crystalloid resuscitation.

Am J Physiol 1992;262:435–40. [PMID: 14894670]

DISTRIBUTIVE SHOCK

Distributive shock is so named because of the redistribution

of blood flow to the viscera. The three types of distributive

shock commonly treated in ICUs are septic, anaphylactic,

and neurogenic shock.



Septic Shock

ESSENTIALS OF DIAGNOSIS



Increased cardiac output in the face of decreased blood

pressure.



Decreased peripheral oxygen consumption.



Decreased systemic vascular resistance.



Decreased ventricular ejection fraction.



Associated multiple organ system failure.

General Considerations

The incidence of septic shock has been increasing in the United

States over the past several years. Approximately

100,000–300,000 people develop bacteremia each year, and

one-half of these patients progress to septic shock. The overall

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SHOCK & RESUSCITATION

231

mortality rate from septic shock is between 40% and 60%.

Higher death rates occur in the aged and in those with compro-

mised immune status as a result of trauma, diabetes, malignancy,

burns, cirrhosis, or treatment with antitumor chemotherapeutic

agents. Aerobic gram-negative bacillary infections are the most

common cause. The predominant organisms are Escherichia coli

and Klebsiella. Gram-positive organisms such as staphylococci

and fungi also may cause septic shock.

A. Pathogenesis—It is unlikely that bacteria per se are

responsible for septic shock. Rather, interactions between their

products and normal host defenses probably elicit the usual

reactions. Gram-negative organisms have complex walls com-

posed of lipopolysaccharides and proteins. Endotoxin is a

lipopolysaccharide component of the outer membrane. It is

composed of oligosaccharide side chains, a core polysaccha-

ride, and lipid A. The chemical and physical structure of the lat-

ter is highly conserved between different bacterial species and is

highly antigenic. In both animal and human studies it has been

shown that infusion of lipid A causes many of the same effects

observed in clinical sepsis. Endotoxin has effects on multiple

regulatory systems, including complement, kinins, coagulation,

plasma phospholipases, cytokines, β-endorphins, leukotrienes,

platelet-activating factor (PAF), and prostaglandins.

Cytokines are a group of proteins produced by white blood

cells in response to a number of stimulating factors. Although

multiple cytokines have been identified, those known to

be involved in the human septic response are TNF and

interleukin-1 (IL-1), IL-2, and IL-6. These agents are likely to

have both beneficial and deleterious effects. Increased levels of

TNF, IL-1, and IL-6 have been correlated with a poor outcome.

TNF produces hypotension and decreased ventricular func-

tion in animal studies. The cytokines are known to induce the

release of counterregulatory hormones such as glucagon, epi-

nephrine, and cortisol, which are necessary to support the

response to sepsis. Cytokines responsible for modulation of

the immune response include IL-4, IL-6, IL-10, IL-11, IL-13,

and IL-1Ra (receptor antagonist). Compounds responsible for

amplification of the immune response include IL-8, IL-12, IL-

18, PAF, serotonin, and the eicosanoids.

Circulating endotoxin induces the production of a num-

ber of white blood cell products that arise from the release

of arachidonic acid from leukocyte cell membranes medi-

ated by phospholipase A

. The mobilized arachidonic acid

then can follow one of two pathways: conversion to

leukotrienes via the lipoxygenase pathway or creation of

prostaglandins and thromboxanes via the cyclooxygenase

pathway (Figure 11–1). The lipoxygenase and cyclooxygenase



Figure 11–1. Pathways of arachidonic acid. (Adapted from Holcroft J, Robinson MK: Shock: Identification and management

of shock states. In: Care of the Surgical Patient. Scientific American, 1992.)



CHAPTER 11

232

compounds have distinct actions (Table 11–4). Phospholipase

also releases membrane-bound alkyl phospholipids that

may be converted into PAF, the most potent lipid mediator

known. The actions of PAF include activation of phagocytes

as well as of platelets, production of oxygen-free radicals,

increase of vascular permeability, and decrease of cardiac

output and blood pressure. Cells known to produce PAF

include neutrophils, basophils, endothelial cells, and

platelets.

Several plasma proteases are activated in septic shock.

These include the kinin system, the clotting cascade, and the

complement system. Endotoxin and gram-positive bacteria

both activate the complement cascade via the extrinsic path-

way. The effects of complement activation include (1)

increased vascular permeability, (2) release of toxic oxygen

metabolites by activated phagocytes, and (3) increased

opsonization and phagocytosis by neutrophils and

macrophages. It is likely that the increased vascular perme-

ability so produced plays an important role in the hemody-

namic picture characteristic of septic shock. A correlation

has been demonstrated between increased concentration of

activated complement and mortality rates. Concomitant

activation of Hageman factor (XIIa) may be responsible for

the disseminated intravascular coagulopathy associated with

sepsis. Factor XIIa also may lead to the conversion of

prekallikrein to kallikrein and ultimately to the release of

bradykinin, which causes severe hypotension.

Recent interest has focused on the roles of toxic oxygen

metabolites and nitric oxide. Activated phagocytes produce

oxygen radicals that kill ingested bacteria. When these prod-

ucts leak from the cell, they may cause severe tissue damage.

Endothelium-derived relaxing factor (EDRF) is another

toxic-free radical species. Chemically, it is nitric oxide (NO).

While small quantities of NO may improve blood flow in the

microcirculation, higher concentrations produce vasodila-

tion and hypotension. NO may arise from several cell lines,

including neutrophils, the vascular endothelium, and

Kupffer cells. NO synthetase is induced by both endotoxin

and TNF. It produces NO from

-arginine.

B. Hemodynamic Effects—The distinguishing hemody-

namic features of septic shock are elevated cardiac output,

decreased systemic vascular resistance, and decreased blood

pressure. Tachycardia is partially responsible for maintain-

ing the blood pressure. Earlier investigators described

hyperdynamic and hypodynamic phases of septic shock.

More recent investigations have shown, however, that car-

diac output remains elevated until decreased output devel-

ops as a preterminal event. It is likely that the earlier

observations were made in patients who were inadequately

fluid-resuscitated.

Right and left ventricular ejection fractions are decreased

in septic shock, as is left ventricular stroke work. In contrast

to hypovolemic shock, increasing preload by administering

volume only minimally increases left ventricular stroke

work. This may be due to altered compliance characteristics

of the ventricles. Pulmonary artery hypertension, which fre-

quently develops early, also may be partially responsible for

right ventricular dysfunction. Cardiac adrenergic downreg-

ulation also occurs. The number of receptors and their

affinities are reduced. Patients who recover from septic

shock increase their left ventricular stroke work index,

whereas those who succumb do not. Radionuclide scans

have shown that left ventricular dilation occurs within

1–2 days of the onset of shock. This increased end-diastolic

volume permits a greater stroke volume in the face of

decreased ejection fraction. Left ventricular dilation

improves as patients recover. Despite the ventricular abnor-

malities, the coronary circulation exhibits above-normal

flow, normal myocardial oxygen consumption, and net

myocardial lactate extraction.

The myocardial depressant factor (MDF) of sepsis has

been characterized as a low-molecular-weight protein

(<1000). Patients with cardiac disease and sepsis without

shock fail to exhibit such activity. MDF may originate from

the intestinal tract in patients with hypovolemic shock. The

cytokines and endotoxin have been suspected as the origin of

MDF. However, TNF has a molecular weight of 17,000.

Lipopolysaccharide, IL-1, and IL-2 in high concentrations

Mediator Actions

Prostacyclin (PGI

) Vasodilation

Decreased platelet aggregation

PGE

Vasodilation

Immunomodulation

Platelet aggregation

PGF

Vasodilation

PGD

Vasodilation

Thromboxane A

Vasoconstriction

Increased platelet aggregation

LTB

Chemotaxis

Leukocyte–endothelial cell adhesion

LTC

Immunomodulation

Vasoconstriction

Bronchoconstriction

Increased vascular permeability

LTD

Vasoconstriction

Bronchoconstriction

Increased vascular permeability

LTE

Vasoconstriction

Bronchoconstriction

Increased vascular permeability

Table 11–4. Actions of arachidonic acid mediators.



SHOCK & RESUSCITATION

233

fail to duplicate the effect of MDF. The decrease in circulat-

ing plasma volume owing to increased capillary permeability

is a major influence in the hemodynamic pathophysiology of

sepsis. In addition to actual transudation of fluid from the

intravascular into the interstitial space, peripheral pooling,

hepatosplanchnic venous pooling, and gastrointestinal and

wound losses—along with idiopathic polyuria—also reduce

cardiac preload.

Changes in the pattern of blood flow distribution are

characteristic of septic shock. It was once thought that shunt-

ing of blood through cutaneous arteriovenous pathways was

responsible for decreased peripheral oxygen extraction, but

the anatomic presence of such shunts has not been demon-

strated. Rather, it is likely that a mismatching of blood flow

and metabolic demand occurs. Thus some organs receive

supranormal oxygen delivery, whereas others are rendered

ischemic. This is of particular importance in the splanchnic

circulation, where hepatic venous desaturation has been

reported in septic patients. Oxygen extraction is also

affected, resulting in flow-dependent oxygen consumption. A

normal or elevated mixed venous oxygen saturation and

decreased arterial-venous oxygen content difference is pres-

ent. Lactic acidosis may indicate the presence of pathologic

oxygen delivery-dependent consumption. It is unlikely that

oxygen utilization is limited by mitochondrial dysfunction.

C. Metabolic Abnormalities—The extent of the metabolic

response to sepsis depends not only on the duration and

severity of the illness but also on the premorbid nutritional

and immunologic status. Even though systemic oxygen con-

sumption is decreased, the metabolic rate in sepsis is

markedly elevated. Mixed fuels serve as the energy source,

with an increase in the respiratory quotient (RQ) to between

0.78 and 0.82. Hepatic glucose production is markedly

increased, with lactate and alanine serving as the major glu-

coneogenic precursors. Hyperglycemia is common, as is

insulin resistance. The elaboration of catechols in

response to the cytokines induces lipolysis, although

ketosis is reduced as a result of decreased hepatic production.

Hypertriglyceridemia may occur as a result of increased

hepatic synthesis and decreased lipoprotein lipase activity.

Protein turnover is greatly increased as a result of the break-

down of skeletal muscle, connective tissue, and visceral pro-

teins as acid sources. Branched-chain amino acids serve as

the preferred fuel source for skeletal muscle. Production of

acute-phase reactants is increased, whereas production of

albumin and transferrin is decreased.

D. Multiple-Organ Failure—Septic shock affects virtually

all organ systems (Table 11–5). Although the exact mecha-

nism responsible is not clear, this may result from microvas-

cular injury and local inflammatory responses. Ischemia

results from tissue hypoperfusion as blood flow is redistrib-

uted away from tissues with high metabolic demands.

The usual progression of organ system failures is pul-

monary, hepatic, and renal. The mortality rate is propor-

tionate to the number of organ systems that fail and reaches

80–100% when three or more systems are involved.

Respiratory failure occurs in 30–80% of patients with sep-

tic shock and usually is in the form of ARDS. Hypoxemia

refractory to increasing levels of support is characteristic.

An elevated intrapulmonary shunt (

Qs/

Qt) makes the

hypoxia resistant to increased concentrations of inspired

oxygen. Pulmonary hypertension, increased extravascular

lung water, and decreased pulmonary compliance accom-

pany the syndrome. Respiratory muscle fatigue and

depressed diaphragmatic contractility further complicate

the situation.

Liver failure is manifested as hyperbilirubinemia and ele-

vation of the aminotransferase and alkaline phosphatase

concentrations. Decreased hepatic amino acid clearance and

an elevation of serum amino acid concentrations are preter-

minal events. Histologic examination reveals intrahepatic

cholestasis with minimal necrosis.

Renal failure may occur as a consequence of hypotension,

from nephrotoxic drug administration (eg, aminoglycosides

and amphotericin B), or from intrarenal corticomedullary

shunting.

Clinical Features

A. Symptoms and Signs—Septic shock is classically defined

as a mean blood pressure of less than 60 mm Hg (systolic

pressure <90 mm Hg)—or a decrease in systolic blood pres-

sure of more than 40 mm Hg from baseline—in a patient

with clinical evidence of infection. Accompanying findings

include fever or hypothermia, tachycardia, and tachypnea.

Patients are frequently obtunded. The skin may be warm if

hypovolemia is not present.

If a pulmonary artery catheter is placed for monitor-

ing, an elevated cardiac output in the face of decreased

systemic vascular resistance will be found. When

decreased cardiac output is noted, hypovolemia should be

suspected. Increased pulmonary artery pressures are com-

mon as a result of vascular reactivity and increased pul-

monary vascular resistance. A pulmonary artery catheter

capable of ejection fraction measurement will indicate a

decrease in right ventricular ejection fraction and stroke

volume. The left ventricular stroke work index is similarly

depressed. Pulmonary capillary wedge pressure (PCWP) is

usually low or normal. Volume infusion to increase the

PCWP generally produces only minimal increases in car-

diac output.

B. Laboratory Findings—Leukocytosis with an increased

percentage of juvenile band forms is the usual finding.

Neutropenia occurs in a small percentage of patients and

portends a poor outcome. Disseminated intravascular coag-

ulation (DIC) with increased prothrombin time, elevated

fibrin split products, and decreased fibrinogen concentration

are also common. Thrombocytopenia occurs in 50% of

patients and may be due to endothelial adherence of platelets

to reactive vascular endothelium. Overt bleeding is noted in

less than 5% of patients.



CHAPTER 11

234

Indicators of Dysfunction

Degree of Dysfunction

Mild Moderate Severe

Respiratory tract Pa

, F

, Pa

, PEEP number of

days on ventilator; peaks airway pres-

sure; use of high-frequency

ventilation or extra-corporeal

membrane oxygenation

>250 Pa

150–250 Pa

<150

Kidneys Creatinine level, creatinine clearance,

BUN, need for dialysis to regulate

serum potassium and bicarbonate

Creatinine <1.5 mg/dL Creatinine 1.5–3.0 mg/dL Creatinine >3.0 mg/dL; need

for dialysis

Liver Bilirubin, albumin, cholesterol, ALT,

AST, γ-glutamyltransferase, alkaline

phosphatase, ammonia

Bilirubin <3 mg/dL Bilirubin 3–8 mg/dL;

elevation of transami-

nases or alkaline phos-

phatase to twice normal

values

Bilirubin >8.0 mg/dL;

elevation of serum ammonia

Gastrointestinal tract Stress-related mucosal ulceration and

bleeding, mucosal acidosis, failure of

pH regulation, volume of nasogastric

drainage, ileus, diarrhea, intolerance

of enteral feeding, acalculous

cholecystitis, pancreatitis

Nasogastric drainage

<300 mL/24 h, diarrhea

in response to enteral

feeding

Nasogastric drainage

300–1000 mL/24 h,

visible blood in drainage

fluid

Nasogastric drainage >1000

mL/24 h, upper GI bleeding

necessitating transfusion,

acalculous cholecystitis,

pancreatitis

Heart Supraventricular arrhythmias, elevated

pulmonary artery wedge pressure and

mean arterial pressure, reduced ven-

tricular stroke-work index, requirement

for inotropes or vasopressors to main-

tain adequate mean arterial pressure

Development of super-

ventricular tachycardias

with heart rate <140

beats/min and no fall in

mean arterial pressure

PAWP 16–30 mm Hg;

requirement for dopamine

or dobutamine at dosage

of <10 μg/kg/min to

maintain satisfactory car-

diac output and PAWP

Requirement for vasopres-

sors (eg, dopamine, epi-

nephrine, norepinephrine,

phenylephrine, vasopressin)

to maintain mean arterial

pressure >80 mm Hg

Central nervous

system

Glasgow Coma Scale score, especially

on components reflecting level of

consciousness

Glasgow score 13–14 Glasgow score 10–12 Glasgow score ≤9

Hematologic system Thrombocytopenia, elevated PT and

PTT, elevated fibrin degradation

products

Platelet count

>60,000/mL

Platelet count

20,000–60,000/mL;

mild elevation of PT or

PTT in absence of

anticoagulation

Platelet count

<20,000/mL

Metabolic and

endocrine systems

Insulin requirements, levels of T

and

reverse T

Insulin requirement ≤1

unit/h

Insulin requirement

2–4 units/h

Insulin requirement

≥5 units/h

Immunologic system Impaired DTH responsiveness, reduced

in vitro lymphocyte proliferation,

infection with ICU pathogens

(eg,

S. epidermidis

candida

pseudomonas

enterococcus

)

Reduced delayed type

hypersensitivity reactivity

Cutaneous anergy Cutaneous anergy, recurrent

infection with ICU pathogens

Wound healing Wound infection, impaired formation

of granulation tissue, would

dehiscence

Wound infection Impaired formation of

granulation tissue

Decubitus ulcers wound

dehiscence

From Holcroft J, Robinson MK: Shock: Identification and management of shock states. In: Care of the Surgical Patient. Scientific American,

1992.

Table 11–5. Recognition and assessment of organ system dysfunction.



SHOCK & RESUSCITATION

235

Hyperglycemia is common and probably reflects the

action of counterregulatory hormones such as epinephrine,

cortisol, and glucagon. Elevation of the serum glucose con-

centration in a patient receiving intravenous hyperalimenta-

tion may be the first indicator of impending sepsis.

Hypoglycemia is frequently a preterminal event. Increased

lactate concentration is common and reflects cellular hypop-

erfusion. Liver chemistries reveal an increase in bilirubin,

aminotransferase, and alkaline phosphatase concentrations.

Mixed substrate fuel consumption increases the respira-

tory quotient to near 0.8. Hypermetabolic protein turnover is

reflected by a negative nitrogen balance. Total serum amino

acid levels are increased with the exception of branched-

chain amino acids (eg, leucine, isoleucine, and valine), which

are decreased.

Arterial blood gas determinations typically indicate mod-

erate hypoxemia and metabolic acidosis. Unless severe respira-

tory muscle weakness is present, Pa

is usually normal or

only minimally elevated. The extent of arterial hypoxemia is

related to the severity of the accompanying respiratory distress

syndrome. The decrease in bicarbonate concentration may

be greater than the increase in lactic acid level, which may be

increased owing to both cellular metabolic failure and failure

of the liver to clear excess production. Blood lactate levels have

been shown to have greater prognostic value than oxygen-

derived variables. Venous blood gases reveal an increased

hemoglobin saturation. Although peripheral oxygen delivery

is elevated, peripheral oxygen consumption and oxygen

extraction are depressed. The arterial-venous oxygen content

gradient is narrowed and may be less than 3 mL/dL.As volume

is administered and oxygen delivery is increased, a correspon-

ding increase in

also may be noted. This supply depend-

ency of oxygen consumption is characteristic of sepsis.

C. Microbiology—Positive blood cultures are present in

about 45% of patients with the septic syndrome and septic

shock. The frequency of organisms present varies in different

studies, although gram-negative aerobic species usually pre-

dominate. A study found that 26% of patients with aerobic

gram-negative bacteremia developed shock, whereas only

12% of those with gram-positive bacteremia went on to

shock. There are no consistent differences in the laboratory

findings of those with and without positive blood cultures.

Furthermore, the mortality rates in the two groups are about

the same (30% without versus 36% with). Other infecting

organisms include Candida albicans and Bacteroides fragilis.

Fungal infections are particularly common in patients with

disorders associated with systemic immunocompromise

such as diabetes. The prolonged use of antimicrobials and a

history of polymicrobial bacterial infections also predispose

to fungal sepsis.

Differential Diagnosis

The difference between true septic shock and the septic syn-

drome is a matter of degree. The major differential factor is

that hypotension is not part of the septic syndrome. Other

forms of distributive shock include anaphylaxis and neurogenic

shock. A history of recent drug administration in the former

and trauma in the latter should aid in diagnosis.

Hemodynamic and cardiac shock rarely cause differential

problems.

Treatment

A. Early Goal-Directed Therapy—Because of the numerous

strategies available for the treatment of septic shock (BP <90

mm Hg), increased emphasis has been placed on evidence-

based management. To this end, a protocol was developed as

part of an international effort to create guidelines for the

treatment of severe sepsis. The general protocol for such

treatment is outlined in Figure 11-2.

B. Fluid Resuscitation—Restoration of adequate circulating

blood volume is the first and most important therapy for

septic shock. Loss of intravascular volume may be through

capillary leaks, fistulas, diarrhea, or emesis. Patients may not

Tra nsfusion of

red cells until

hematocrit ≥30%

Colloid

Supplemental oxygen ±

endotracheal intubation

and mechanical ventilation

Central venous and

arterial catheterization

Sedation, paralysis

(if intubated), or both

CVP

MAP

ScvO

Goals

achieved

Tra nsfer from

ICU

8–12 mm Hg

≥65 and

≤90 mm Hg

≥70%

Ye s

Crystalloid

Vasoactive agents

Inotropic agents

<65 mm Hg

>90 mm Hg

<8 mm Hg

<70%

≥70%

<70%



Figure 11-2. A general protocol for early goal-directed

therapy in the management of severe sepsis and septic

shock.



CHAPTER 11

236

have been receiving adequate oral intake or may have

received insufficient maintenance intravenous fluid.

Crystalloid is preferred by most physicians as the initial fluid

for resuscitation. Rather than simply increase the infusion

rate, patients should receive boluses of 500–1000 mL of fluid

at a time. Because the extent of peripheral vasodilation may

be massive, these patients may require large amounts of fluid.

A central venous pressure catheter may be inserted to guide

therapy. Bolus administration of volume should be titrated

to maintain central venous pressure between 8 and 12 mm Hg.

If a pulmonary artery flotation catheter is used, PCWP needs

to be elevated to higher than normal levels before an ade-

quate cardiac output and blood pressure are achieved.

Typically, a PCWP of between 10 and 15 mm Hg will be

required. This may call for the administration of several liters

of balanced salt solution. Ongoing capillary leakage calls for

continuing aggressive fluid replacement. Infusion should be

monitored by watching for signs of pulmonary edema and

congestive heart failure. Peripheral edema may be noted and

is a normal consequence of the capillary leak that accompa-

nies the systemic inflammatory response syndrome. The

choice of crystalloid or colloid resuscitation remains contro-

versial. Two meta-analyses that compared albumin and crys-

talloid found that mortality was higher among those who

received albumin. However, some studies have found a trend

toward reduced mortality when albumin was used. Because

there is no clear benefit of either solution at this time, most

clinicians prefer crystalloid solutions because of their

reduced choice and universal availability.

C. Respiratory Support—Many patients with septic shock

will have severe respiratory distress syndrome. They also may

be unable to meet the increased demands of the work of

breathing. Semielective endotracheal or orotracheal intuba-

tion is recommended prior to the development of respiratory

arrest. After intubation, mechanical ventilation always

should be instituted to decrease the work of breathing. Many

patients will require high inspired oxygen concentrations

and positive end-expiratory pressures (PEEP). Inverse I:E

ratio, pressure-controlled, and/or pressure-regulated

volume-control ventilation may be required if pulmonary

compliance is severely compromised. Airway pressure-

release ventilation (APRV) is also useful in those with ARDS

and poor oxygenation. The great advantage of APRV is that

patients can be weaned from it directly without having to

employ other modes. Treatment of respiratory failure is dis-

cussed in Chapter 3.

D. Pharmacologic Support—If intravascular volume resus-

citation fails to restore blood pressure toward normal, phar-

macologic support with pressor drugs is indicated. Target

mean arterial pressure is between 60 and 65 mm Hg,

although the optimal pressure is still debated. It is important

not only to measure arterial pressure but also to evaluate

overall perfusion based on Sv

, urine output, and resolution

of increased arterial lactate. Both peripheral and cardiac

adrenergic receptors appear to be downregulated in sepsis,

making the required dose of pressors higher than otherwise

might be expected. Dopamine and norepinephrine are the

most common pressors used for the treatment of septic

shock. Although dopamine was used often initially in the

past, there has been a trend toward the use of norepinephrine

as the first-choice pressor (see below). Although no large-

scale trials have been completed to determine which agents

are associated with better outcomes, there is some evidence

to suggest that patients who have not received dopamine

have a lower 30-day mortality than those who have.

1. Dopamine—Dopamine is the immediate precursor of

endogenous norepinephrine. Dopamine’s hemodynamic

effects are due to the release of norepinephrine from sympa-

thetic nerves and the direct stimulation of alpha, beta, and

dopaminergic receptors. Approximately 50% of dopamine’s

effect is due to the release of norepinephrine. When com-

pared with dobutamine, dopamine’s effect is less pro-

nounced after endogenous norepinephrine stores have been

depleted. At lower doses (2–5 μg/kg per minute), dopamine

increases cardiac contractility and cardiac output without

increasing heart rate, blood pressure, or systemic vascular

resistance. Renal blood flow and urine output increase in

response to doses of 0.5-2 μg/kg per minute as a result of

selective stimulation of dopaminergic receptors. When doses

reach 10 μg/kg per minute, dopamine has both a

chronotropic and an inotropic effect. At infusion rates in

excess of 10 μg/kg per minute, alpha-adrenergic stimulation

occurs, along with an increase in systemic vascular resistance.

The metabolic effects of dopamine administration include

decreased aldosterone secretion, inhibition of thyroid-

stimulating hormone and prolactin release, and inhibition of

insulin secretion. Because it increases cardiac output,

dopamine can increase pulmonary shunting by augmenting

flow to poorly ventilated lung regions.

After ensuring adequate fluid resuscitation, dopamine

infusion is usually started at a dose of 5 μg/kg per minute

and advanced until blood pressure increases. Used in low

doses with norepinephrine, dopamine’s selective effect on

the renal vasculature may continue to allow adequate urine

production while norepinephrine supports the blood pres-

sure by its vasoconstrictive effect.

2. Dobutamine—Dobutamine has predominantly β-

adrenergic inotropic effects. It has a relatively minor

chronotropic effect. Unlike dopamine, it does not cause the

release of endogenous norepinephrine. It produces less

increase in heart rate and peripheral vascular resistance than

an equally inotropic dose of isoproterenol. It is the pressor of

choice in patients with adequate blood pressure but depressed

cardiac output. Onset of action is within 1–2 minutes, although

the peak effect may not be reached until 10 minutes after

administration. The plasma half-life is 2 minutes. The drug is

methylated and excreted in the urine. Dobutamine tends to

lose its hemodynamic effect after prolonged administration

probably because of downregulation of receptors. However,

dobutamine is a better choice for long-term infusion than