Effects of catecholamines on oxygen consumption and oxygen delivery in critically ill patients

DOI 10.1378/chest.100.6.1676 1991;100;1676-1684Chest

R Chioléro, J P Flatt, J P Revelly and E Jéquier patients.consumption and oxygen delivery in critically ill Effects of catecholamines on oxygen

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1676 Catecholamines and 02 Consumption in Critically III Patients (Chiolem et a!)

critical careEffects of Catecholamines on Oxygen Consumptionand Oxygen Delivery in Critically Ill Patients*Ren#{233}Chiole’ro M.D.; Jean-Pierre Flatt Ph.D.;t Jean-Pierre Revelly M.D.;

and EricJequier M.D.t

(Chest 1991; 100:1676-84)

no, = oxygen delivery; EE en�rgy expenditure; MVo,myocardial oxygen consumption; Vo, = oxygen consumption

C atecholamines are widely used in the management

ofpatients whose cardiovascular system is failing.

Indeed, they figure among the most commonly used

pharmacologic agents in critically ill patients. The

positive effects of catecholamines on cardiac function,

tissue perfusion and oxygenation are well known. ‘‘#{176}

Parallel to their effects on systemic hemodynamics,

these agents exert numerous metabolic and endocrine

effects. 11-12 The most important metabolic effects in-

dude elevation of hepatic glucose production, stimu-

lation oflipolysis, increases in plasma glucose, lactate,

potassium and free fatty acids levels, as well as

elevation of the resting metabolic rate . � � The latter is

related to a direct action of catecholamines on 02

consumption (c�o2) reflecting heat production in van-

ous tissues, which is independent of their hemody-

namic effects in normal conditions.”3 In clinical

practice, the distinction between these different ef-

fects of catecholamines on whole body V02 is often

neglected and it is commonly believed that any

increase in Vo2 is associated with improvement in

systemic hemodynamics and tissue oxygenation. This

statement is not always true.

The aim of this review is to comment on the effects

ofcatecholamines on oxygen consumption and energy

metabolism, including their implications for clinical

practice. This review has three sections devoted (1) to

an evaluation of the concept of energy utilization and

heat production, (2) to the effects of catecholamines

on 02 uptake in various tissues and its mechanisms,

and (3) to the effects of catecholamines on 02 con-

sumption in critically ill patients in whom 02 delivery

is often inadequate.

5From the Surgical Intensive Care Unit, Department of Anesthe-siology, University Hospital, Lausanne, Switzerland.

tlnstitute of Physiology, Faculty of Medicine, Lausanne.Supported by a grant from Hausmann-Vifor, Geneva, Switzerland.

Reprint requests: Dr. Chiolero, Senice de Anesthesiologie, CHU1�I�iiusanne, Switzerland 1011

ENERGY EXPENDITURE AND THERMOGENESIS

Oxygen consumption and energy expenditure are

closely correlated physiologic �4 In normal

subjects, Vo2 is usually assessed using indirect calorim-

etny, which relies on direct measurement of body gas

exchange . ‘5 In clinical conditions, �#{176}2 �S often calcu-

lated from cardiac output and anteriovenous differ-

ences in 02, by means of the Fick principle. The heat

released by the oxidative processes can then be

calculated using an energy equivalent for the con-

sumed 02, which is dependent on the respiratory

quotient, the ratio between CO2 production and V02.

In subjects in thermal equilibrium, resting energy

expenditure determined by indirect calorimetry is

equivalent to heat production measured by direct

calorimetry. ‘5

Energy Utilization

Energy is utilized in the body to perform electro-

chemical, mechanical and synthetic work. These proc-

esses maintain electrochemical gradients through cell

membranes, allow muscular activity, and the synthesis

ofmacromolecules such as proteins and glycogen. The

release of energy from substrates is coupled to ATP

synthesis, while most of the cellular energy requiring

processes are dependent on ATP hydrolysis. The

energy expended by the body is ultimately converted

into heat, which must be dissipated. Heat production

is therefore the end product of energy utilization in a

resting subject. During exercise, however, a fraction

of energy is transformed into external 16

Energy utilization by the body is illustrated in

Figure 1 . Gross energy refers to the energy content

of nutrients, ie, their heat of combustion. A small part

of energy is lost in feces and urine (usually about 5

percent, except in patients with gastrointestinal or

renal diseases), leaving the metabolizable energy.

The transformation of metabolizable energy into

chemical and mechanical energy is always associated

with heat production and dissipation.’6 When discuss-

ing energy metabolism, it is useful to understand how

the energy released by substrate oxidation is utilized



CHEST I 100 I 6 I DECEMBER, 1991 1677

GROSS ENERGY

F-’- URINARY AND FECAL LOSSES

METABOUZABLE ENERGY (ME)

I___.. HEAT PRODUCTION (35% OF ME)

O2��J

�-*. C02, UREA, etc

ADP 4 ! � HEAT PRODUCTION

CHEMICAL WORK

MECHANICAL WORK

t__+.INTERNAL WORK-�’ HEAT PRODUCTIONEXTERNAL WORK

Ficuan 1. Fate ofenergy in the body.

(Fig 1). Jequier and Flatt’6 have calculated the effi-

ciency ofvarious energy-transforming processes. They

found that while performing aerobic work, 65 percent

of the energy released by oxidation of substrates is

transformed into chemical energy in the form of high

energy bonds in AlP, and that 35 percent ofthe energy

is released as heat during the process of oxidative

phosphorylation. The overall efficiency of aerobic

exercise was found to be 27 percent, indicating that

40 percent ofthe energy liberated by AlT breakdown

was converted into mechanical work (65 percent X 40

percent = 27 percent). This example illustrates the

concept that metabolic processes are always associated

with the transformation of energy into heat; heat is

first released when KIT is synthesized, and then

further produced when KIT is hydrolyzed.

Energy Expenditure

Overall, energy expenditure can be attributed to

three major components in the normal adult subject:

basal EE, physical activity EE, and increments in the

energy expenditure above basal metabolic rate due to

various physiologic and unphysiologic causes (Fig 2).

The latter include the thermic effect offood, exposure

to cold, or the effects of psychological influences. In

growing children, the energy devoted to growth

slightly increases the metabolic rate. In critically ill

patients, one must also consider the effects of illness

and fever which commonly increase metabolic rate,

as well as the effects of drugs and supportive treat-

ments. Basal EE refers to the energy expended by

resting healthy subjects while in the postabsorptive

state under standardized conditions. Basal EE is

dependent upon the mass of active cells and is the

result of the biochemical processes devoted to the

maintenance ofvital functions. Liver, heart, brain and

ENERGY RECOVERED IN ATP(65% OF ME)

kidney metabolism account for 60 to 70 percent of

basal EE.’7 In clinical conditions, the patients are

never in truly basal conditions. One usually refers to

resting energy expenditure, which is a more appropri-

ate term. Resting EE is the rate of energy expended

by resting healthy or ill subjects in usual clinical

conditions, as in a nonthermoneutral environment,

and while receiving drugs or supportive treatments,

including nutritional support.

Autonomic and Endocrine Regulation of

Energy Expenditure

Energy expenditure is influenced by numerous

physiologic factors, among which the thyroid hormone

and the sympathetic nervous system play key roles.

Thyroid hormone is the primary endocrine regulator

ofbasal EE, which is not markedly influenced by the

activity of the sympathetic nervous system, as shown

by the weak effect of beta-blocking agents on 18 By

contrast, the sympathetic nervous system exerts a

regulatory action on the metabolic processes related

to nutrition (diet-induced thermogenesis), environ-

mental changes (nonshivering cold-induced thermo-

genesis) and to fflness.l3,l�m In addition to catechola-

mines and thyroid hormone, coi-tisol and glucagon

have been shown to exert additional effects on resting

energy expenditure .�

EFFECTS OF CATECHOLAMINES ON OXYGEN

CONSUMPTION IN NORMAL SUBJECTS

It is long known that catecholamines increase resting

02 consumption in animals and man. Since the begin-

ning ofthe century, various authors have clearly shown

that epinephrine directly influences 1�O2 and heat

production.Z However, contradictory results have oc-

casionally been found with norepinephrine, due to

problems of experiment and measurement. More

recent studies using continuous infusion of catechola-

mines and the increasingly available technique of

indirect calorimetry have confirmed the thermogenic

effect of epinephrine, norepinephrine and dopa-

mine.’9�’�”#{176} In addition, studies in which stepwise

increments in catecholamine infusion rate were per-

formed have shown a dose-related calorigemc ef-

fect.� The most important results are summarized

inTable 1.

The thermogenic effect reported in the literature

for catecholamines is variable: epinephrine produced

thermogenic effect ranging between 15 and 37 percent

ofresting EE in normal subjects, while norepinephnine

and dopamine induced thermogenic effect of 21-23

percent and 8-15 percent of resting EE, respec-

tively.’9’�� No data are yet available on the calori-

genic effect of dobutamine and dopexamine which at

present are commonly used on intensive care patients.

The maximal effect ofcatecholamines on ‘��O2 and EE

has been assessed for epinephrine by Sj#{246}str#{246}met al.�



1678 Catecholamines and 02 CU�Pt�0n in CrItically III Patients (Chiolem eta!)

Table 1-Effrcts ofCateclsolamines on Basal Vo’, on Rate-&essure Product (RPP) and on the Contribution ofMyocardial O� Consumption (MVo�) to Vo, Changes in HeOJ*hIJ Subject.

Authors Catecholamine

Dose

�g.kg’.min’

Resting Vo2or EE

Vo2(%)

�RPP

(%)MVo, Contribution

to � Vo, (%)

SteinbergetaiM NEPI 0.13-0.31 205 mlmin� +21 - -Svedmyr et alv NEPI 0.10 3.4 ml#{149}kg”min’ + 15 + 11 1.1

Shettyetai’#{176} NEPI 0.15 - +10.3 - -Svedmyr et alv EPI 0.10 3.7 ml#{149}kg”min’ +23 + 72 7.2

Wilmoreetal’� EPI 0.10 33.8kcal’m’4r’ +37 - -

Sj#{246}str#{246}met al� EPI 0.10 43 W.m’ +29 +35 3.5

BesseyetaP’ EPI 0.03 219ml”min’ +13 +50 5.0

R#{252}ttimann et al� DOPADOPA

5.010.0

216 mhnin’211m}’min’

+6+15

+22+55

2.25.5

NEPI= norepinephrine; EPI = epinephrine; DOPA = dopamine.

They infused increasing doses of epinephnine in

healthy women (0.01, 0.03 and 0.1 p�g.kg fat free

mass’#{149}min�) and established the dose-response

curve for the thermogenic effect. They found a maxi-

mal increase in �‘#{176}2 of 35 percent. Although no data

are yet available on the maximal thermogenic effect of

other catecholamines, epinephrine appears to be the

most thermogenic. This is also the case for the effects

on hepatic glucose production and on adipose tissue

lipolysis which are markedly stimulated by epineph-

rine.�d�� The plasma molar concentration of dopa-

mine required to induce a 15 percent elevation of

Vo2 is 150 times greater than for epinephnne and

norepinephrine.m This point illustrates the great dii’-

ference in the thermogenic power of dopamine and

epinephrine, which is probably related to the differ-

ence in their beta-adrenergic activity.

Mechanisms ofCatecholamine-induced Thermogenesis

The calorigenic action of catecholamine is related

to the stimulation ofthe beta adrenergic receptors.”3

No thermogenic effect is observed following dopami-

nergic- and alpha-adrenergic 19,m The ef-

fects of the sequential stimulation of the alpha-, beta-

and dopaminergic adrenergic receptors was recently

studied by R#{252}ttiman et al.� They infused in normal

subjects sequential doses of dopamine (2.5, 5.0 and

10 p.g’kg ‘min ‘), which is known to produce a dose-

dependent stimulation ofthe three main types of post-

synaptic adrenergic receptors. They observed hemo-

dynamic changes characterized by increases in heart

rate, stroke volume, cardiac output and oxygen deliv-

ery (Doe), but no thermogenic effects at the lowest

dose, where a dopaminergic effect was predominant.

At 5.0 and 10 p�g.kg ‘min ‘ , they noticed elevation

of both Vo2 (+ 6 and 15 percent respectively) and

Do2, illustrating the effect of beta-adrenergic stimu-

lation.

The thermogenesis related to catecholamines is a

complex phenomenon due to the numerous direct and

indirect effects that they exert on the tissues of the

whole organism. Various organs have been shown to

increase their 02 consumption following beta-adrener-

gic stimulation.31’� Furthermore, the elevation of body

temperature and the stimulation ofthe central nervous

system produced by catecholamine action may also

influence the resting Vo2 ofthe orgaifism.’3”9”�’

In normal resting subjects, �O2 is independent of

cardiac output and 02 delivery, contrary to patients in

a state of shock.� The contribution of myocardial ‘�O2

(M�o2) to catecholamine-induced thermogenesis is

small.

It can be estimated via the changes in the rate-

pressure product.� Myocardial ��O2 at rest is respon-

sible for about 10 percent of the whole body 02

17 Catecholamines increase the rate-pres-

sure product and thus M’�o2; the effect on the whole

body ‘#{176}2 is limited, ranging between 1 and 10 percent

(Table 1). The contribution of respiratory muscles �

to catecholamine thermogenesis is minimal, due to

the low resting V02 of these muscles� in normal

subjects.

In newborns, sympathetic stimulation increases 02

consumption of brown adipose tissue and whole bodyresting metabolic rate.3’ Very small amounts of brown

adipose tissue are still present in adult man, although

their physiologic importance is debated.3’

The cellular mechanisms of thermogenesis are also

incompletely elucidated. They may involve intra- and

extra-mitochondrial processes.� Intra-mitochondrial

thermogenesis could be related to decrease in the

oxidative phosphorylation efficiency via partial Un-

coupling of the respiratory chain. Such a mechanism

is known to occur in brown adipose tissue. Beta-

adrenergic stimulation induces lipolysis and the free

fatty acids so produced serve as fuel for thermogenesis

as well as an intracellular signal for the activation of a

“proton-conductance mechanism” which elevates the

permeability ofthe inner mitochondrial membrane to

the inward movement of protons and thus uncouples

the mitochondria.3’ Several extra-mitochondrial proc-

esses requiring ATP hydrolysis have been de-

scribed.31’�These include shivering, substrate cycling,

and Na-cycling at the plasma membrane, processes



0

I-

cJ

50

40

30

20

10

0

Activity

Stimulants TE

Cold TB

Food TE

Activity

Treatment TE

Cold TB

Food TB

Illness TE


leading to AlT utilization and enhanced heat produc-

tion. Substrate cycling has been shown to contribute

to the increase in resting metabolic rate and thermo-

genesis in severely burned patients, bu� #{244}#{241}lyto the

extent ofa small part ofthe EE changes.�

In assessing the use of the catecholamine-induced

increment in Vo2 by the organism in a normal subject,

it is apparent that a large part leads to heat production

and dissipation (true thermogenesis), and only a small

part to extrametabolic effects, such as the elevation of

myocardial 02 and respiratory muscles’ 02 consump-

tion. The effects of catecholamine on V02 and meta-

bolic rate in normal subjects can thus be considered

the prototype ofa thermogenic process.

THE CRITICALLY ILL PATIENT

Numerous clinical studies have shown that catechol-

amines also increase Vo2 in critically ill patients (Table

2). “�‘� However, this effect is more variable than in

normal subjects and occasionally decreases in �#{176}2

have been observed in individual cases with low

cardiac output syndromes unresponsive to catechola-

mine infusion.4’7

In the critically ill, catecholamines influence body

V02 via two main mechanisms (Fig 2): (1) as in normal

subjects, they stimulate the tissue 02 consumption

directly (a thermogenic action); (2) in patients with

low 02 delivery or inadequate 02 extraction, they

affect the Vo2 via their effect on tissue 02 delivery. In

addition, they may also influence body Vo2 by altering

the regional distribution of blood flow, although no

clinical data are presently available on this point.�

Measurement of Oxygen Consumption and

Metabolic Rate

Accurate measurements of 02 consumption and

60_I

Co2 production are difficult in clinical conditions,

particularly in patients on mechanical ventilation.’#{176}

The Fick method is commonly used in intensive care

patients. It requires a pulmonary artery catheter to

measure cardiac output by thermodilution and draw

out the mixed venous blood to determine its 02

content. The accuracy of this technique of measure-

ment is ± 10 percent at best; this is due to the

cumulative measurement errors related to cardiac

output, arterial 02 content, and venous 02 content.4’

This technique does not account for the lung paren-

chyma 02 consumption, a factor which may be signif-

icant in acute lung disease. Furthermore, the Fick

method should not be used to determine the relation-

ship between V02 and Do2 because these two parain-

eters are both derived from the cardiac output and 02

arterial content values. In such conditions, the varia-

bles are not independent and there is an overestima-

tion of the correlation between these variables due to

a mathematical coupling phenomenon.’�’

The gas exchange technique measures the ‘�O2 of

the whole organism, including the lungs. It implies

that the patient is in a steady state, with identical

tissue and pulmonary gas exchange. Even brief

changes in ventilation may rapidly modify the body

gas stores and therefore invalidate this assumption. In

patients on mechanical ventilation, this technique

requires a stable inspiratory 02 concentration below

60 percent, and no gas leakage in the system . if these

requirements are satisfied, this technique has been

shown to have a fair accuracy in the 1-5 percent

range .

The difficulties and limitations in measurement of

V02 in the acutely ill patient should be taken into

consideration when analyzing the effects of agents

such as catecholamines on ‘�JO2 and metabolic rate.

Activity

Treatment TE

Cold TBFood TE

Illness TE

D02-dependent

Normal suject Critically iLl

flow dependentpatient

Critically illhypermetabolic

patient

Ficuas 2. Components of 24-h energy expenditure (EE) in normal, critically ill #{176}2delivery-dependentand critically ill hypermetabolic patients. TE = thermic effect.



0

E

0

C

80

0

60 a.

0

‘.U CJ

a.

20 �

E

C

E

E

C0

0.E

InC00

0

200�

175�

150’

125�

100’

p

0 200 400 600 800 1000 1200

02 delIvery (mI.mIn1.m2)

Ficuax 4. Effects ofcatecholamines or propranolol administration

on the VoJDo, relationship in normal and critically ill subjects.Normal subjects (O----O); cardiogenic shock (D-.D); pulmo-nary embolism (D-�-#{149}D); septic shock (#{149}#{149});pre and post-operative patients (A-#{149}-A); head injury (<)- <>).Sources: a) Ruttimann et al,� dopamine; b) Muller et al,’ dopamine;c, d) Richard et al,� dopamine, dobutamine; e, f, g) Jardin et al,2

dopamine; h) Jardin et al,� dobutamine; i) Mackenzie et al,’#{176}epi-

nephrine; j) Edwards et al,8 norepinephrine± dopamine± dobuta-mine; k, m) Shoemaker et al,� dopamine, dobutamine; 1) Shoemakeret al,6 dobutainine; n) Mathru et al,� dobutamine; o) Jardin et al,’dobutamine; p) Bobertson et al,’#{176}propranolol.

Effects of Catecholamines on 02 Delivery

1680 Catecholamines and 0, Consumption In Critically III Patients (chiolero eta!)

Tissue 02 delivery is dependent upon changes in car-

diac and respiratory function, and blood hemoglobin

concentration. It is calculated using the simple math-

ematical formulas: Do2 = Ca02 x QT x 10(ml#{149}min ‘) =

(Hb x Sa02 X 1 .39) + (0.003 x Pa02), where Ca02 is ar-

terial 02 content (ml#{149}100ml ‘), QT= cardiac output

(L’min - ‘), Sa02 = arterial 02 saturation (%),Hb =

hemoglobin concentration (g’lOO m1 ‘ and Pa02 =

arterial 02 partial pressure (mm Hg). Catecholamines

affect Do2 via their effects on cardiac and respiratory

functions. These are mediated via the stimulation of

the adrenergic receptors. Beta-adrenergic stimulation

causes increase in heart rate, myocardial contractility,

stroke volume, cardiac output and Do2, both in normal

subjects and in most clinical conditions. 110.29 However,

the positive action on cardiac output may be slightly

counterbalanced by the increase in intrapulmonary

shunt and the resulting decrease in Ca02, produced

by beta-adrenergic stimulation.� Moreover, moderate

increases in calculated intrapulmonary shunt fraction

have been observed following dopamine and dobuta-

mine infusion in critically ill patients,2’3’9 although

other studies have failed to find any change.4’5’6”#{176}

Effects ofCatecholamines on Oxygen Cor�umption

as Related to Oxygen Delivery

The well known relationship between oxygen de-

livery (Doe), oxygen extraction ratio (ERo2) (the per-

centage of delivered 02 extracted by the tissues) and

Vo2 in the resting subject� is shown in Figure 3.

The exact formula is as follows: �

DO,, X ERo2 = Ca02 X Q’r x ERo2. The normal values

for Do2 are in the range 500-600 ml’min ‘#{149}m2 � At

normal or high levels of Do2, Vo2 is independent of

02 delivered to tissue. When Do2 decreases, due to

failing cardiac or respiratory function or to decreased

hemoglobin concentration, there is an increase in 02

extraction which allows normal Vo2 values to be

maintained. Below a critical level, the increase in 02

extraction cannot fully compensate for the reduction

in Do2. Hence, Vo2 decreases in porportion to

Do2 below the critical Do2 threshold value, a phenom-

enon which is riot observed in normal conditions.�

The critical level at which �O2 becomes independ-

ent of Do2 varies according to species, specific organs,

and physiologic conditions. There are as yet no clear

data on the Do,/Vo2 relationship in normal human

subjects. In anesthetized dogs, the critical Do2 value

is around 10 ml#{149}kg ‘min ‘ during anemia and hypoxic

hypoxia.’� In the anesthetized man during the preby-

pass period for coronary artery surgery, the critical

Do2 value was found to be 330 ml#{149}min “-in 2 or 8.2

ml#{149}kg‘.min ‘ �‘*(� In acutely ill patients, the critical

Do2 value varies widely, according to the specific

disease, and the Do�o2 patterns are often more

0

Oxygen delivery

FIGun� 3. Oxygen consumption versus 0, delivery (-) or 02extraction ( ) in normal subjects, as well as in patients with

abnormal #{176}�extraction (-).

complex than the simple linear relationship observed

in animal studies. Furthermore, the ability of tissues

to extract oxygen may be impaired in certain acute

illnesses, such as ARDS, severe septic states, and

hypovolemic shock.�’47 In such conditions, a patho-

logic dependency on oxygen supply has been de-

scribed where, due to the inefficient tissue 02 extrac-tion, the critical Do2 value is substantially increased

(Fig 3). Critical Do2 value as high as 21 ml#{149}kg’.min’

has been found in patients with ARDS� or with severe

septic states.8’49

Numerous studies have evaluated the effects of

catecholamines on Do2 and V02. The results of some

recent studies in critically ill and normal subjects are

illustrated in Figure 4 and Table 2. The patients



Table 2-Ejfrcts ofCatecholamines and Beta-Blocking Agents on 0, Consumption (Vo’) and O� Delivery (Doe)in Critically Ill Patients and in Normal Humans

VO, (mI.mini��m2) 1)02 (mhnin - ‘#{149}m�-2)

Baseline Baselinetreatment treatment

Authors Clinical Characteristics Catecholamines i� % P % P

Muller et al’ Cardiogenic shock DOPA 112 125 + 12 <0.001 287t 385t +34 <0.001

Jardin et al� Septic shock hyperdynamicSeptic shock hypodynamicSeptic shock, hypovolemic hypodynamic

DOPADOPADOPA

172 179 +4128 141 + 10122 149 + 22

NS<0.01<0.01

524 686

255 435298 536

+31+ 71

+80

<0.05

<0.01

<0.01

Jardin et al� Septic shock DOBU 132 140 +6 NS 497t 675t +36 <0.001

Richard et al� Cardiogenic shockCardiogenic shock

DOPA

DOBU

86 110 +2892 96 +4

<0.05

NS

315t 455t

333t 420t

+44

+26

<0.05

<0.05

Jardin et al’ Pulmonary embolism + shock DOBU 130 155 + 19 <0.05 228 430 + 89 <0.01

Shoemaker et al6 Critically ill surgical patients DOBU 131 157 + 20 <0.01 521 646 + 24 <0.01

Shoemaker et al� Postoperative surgical patient

Ikstoperative surgical patientDOPA

DOBU136 143 +5139 161 + 16

NS<0.05

518 630493 690

+ 22

+ 40

NS

<0.05

Edwards et al8 Septic shock NE ± DOBU ± DOPA 130 169 +30 <0.05 605 843 + 39 <0.05

Mackenzieetal’#{176} Septic shock EPI 116 133 + 15 NS 382 596 +56 <0.01ROttimann et al� Normal subjects DOPA 136 155 + 14 <0.01 790 986 + 25 <0.01

Robertson et al� Head injury PROPRA 201 164 -32 <0.05 942 697 -26 <0.05

Welle et a118 Normal subjects PROPRA 254 256 0 NS - - - -

DOPA=dopamine; DOBU =dobutamine; EPI =epinephrine; PROPRA=propranolol.

tCalculated assuming a value of 17.5 ml/100 ml for CaO,.


received catecholamine therapy in the management

of cardiogenic shock,”4 septic shock,238�0 pulmonary

embolism with shock,5 penoperative or posttraumatic

circulatory failure.6’9’� The DoJ�o2 responses to

dopamine, dobutamine, epinephrine, and to norepi-

nephrine combined with dopamine ± dobutamine are

shown. In addition, the responses to dopamine in

normal subjects� and to beta-blockade in hyperdy-

namic patients with severe head injury2#{176}have also

been reported.

Keeping in mind the large individual variations, it

is clear from Figure 4 that catecholamines produced

increases in both Do2 and V02 in most ofthese studies,

whatever the baseline level of Do2 (low, normal or

high).

As expected, increases in both Do2 and �#{176}2 were

produced by catecholamines in patients with low

cardiac output syndromes”4 (Oo2<500 ml#{149}min ‘m 2).

In septic shock�’3’8”#{176} a critical condition associated

with an abnormal ability to extract 02, similar

responses were noticed in patients with normal or

elevated Do2 (Do2>500 ml.min1m2). Thus, in all

these conditions, Do2 was below the critical level, and

Vo2 was directly dependent on Do2 and thereby

enhanced by catecholamine administration.

In critically ill surgical patients,6’9’� simultaneous

changes in both Do2 and V02 were also observed in

patients with normal or elevated Do2. Many of these

patients were treated for acute illnesses associated

with a pathologic dependency of ‘�O2 on Do2, thus

explaining this relationship between these parameters.

Moreover, independent changes of V02 and Do2 did

probably also occur in others with unimpaired 02

extraction ability.

Thermogenic Effect of Catecholamines

In normal subjects and in patients with 1302 over

the critical value, the ��1O2 response to catecholamines

is not related to their effect on systemic hemodynam-

ics. In such conditions, catecholamines exert simulta-

neous and independent influences on cardiac function

and tissue metabolism. The main effect on �O2 is

caused by the thermogenic action, while the Do2

changes are produced by the stimulation of cardiac

function. This results in the disappearance of the

plateau in the Do�JVo2 response curve, as shown in

Figure 4. The simultaneous change in both V02 and

Do2 following catecholamine administration in sub-

jects with normal cardiac function is therefore not

related to a state of dependency of �‘O2 and Do2,

although this point still needs to be established clearly.

As yet, there are no data in patients with low cardiac

output states distinguishing the effects of adrenergic

agents on Vo2 due to a direct increase in the metabolic

rate from those related to Do2 enhancement. In

traumatized and in many acutely ill patients withnormal cardiovascular function, it has long been

demonstrated that sympathetic nervous system hyper-

activity plays a key role in the elevation of resting ‘�02

which is typically observed.’9’�#{176}’21’�’49 Such hypermet-

abolic patients are characterized by large increases in

plasma levels and urinary excretion of epinephrine

and norepinephrine.’� Their resting �O2 has been

found to be increased up to a maximum of200 percent

of normal resting �9 The magnitude of the

response varies according to the type of injury and its



1682 Catecholamines and 02 Consumption in Critically III Patients (Oliloleto eta!)

‘9

Another way of evaluating catecholamine-induced

thermogenesis is by administrating beta-blockers. Pro-

pranolol produced a mean reduction of V02 of 12

percent in the burned patients studied by Breitenstein

et al� and a statistically nonsignificant decrease in

Vo2 in the severely burned patients reported by Wolfe

et � In the study by Wilmore et al,’� propranolol

combined with phentolamine decreased mean resting

Vo2 by 18 percent in burned patients. Robertson et

alm have evaluated the effects of beta-blockade on

systemic hemodynamics and ‘c�o2 in patients with

severe head injury. They observed a hyperdynamic

cardiovascular state characterized by tachycardia, in-

creased cardiac index and systemic vascular resis-

tances; the Do2 (725 ml’min “in 2) and ‘��o2 (173

ml”min - ‘#{149}m2) were also markedly enhanced . Pro-

pranolol produced a decrease in both Do2 (-27

percent) and Vo2 ( - 18 percent) with no apparent

detrimental effect on tissue oxygenation, as shown by

the stability of the 02 extraction ratio and the mixed

venous Po2 (Fig 4). These results demonstrate clearly

that catecholamines and sympatho-adrenergic hyper-

activity contribute to the thermogenic phenomena

which are present in the hypermetabolic critically ill

patients.

Clinical Relevance

It has been repeatedly shown that decreased body

Vo2 is associated with increased mortality among

critically ill patients under various conditions, par-

ticularly in those with low cardiac output syn-

dromes.m,m,ss Moreover, Do2 and �O2 have been shown

to be better predictors of survival than the usual

hemodynamic parameters.� Bland et ale’ have re-

cently assessed tissue 02 debt (calculated as the

measured minus the estimated Vo2) during the peri-

operative period in 100 high-risk surgical operations.

They observed a strong influence of Vo2 deficit on

survival. Nonsurvivors had a signfficantly higher mean

maximum cumulative �02 deficit (33.5 ± 36.9 (SD)

Lrn2) as compared to survivors (8.0± 10.9 L#{149}m2).

Other studies have produced evidence that supra-

physiologic increases in Do2 and in �TO2 are associated

with improved survival in some categories of pa-

flents.�

Catecholamines are widely used in the critically ill

to improve the failing systemic hemodynamics and

thereby enhance Do2. They are the mainstay of

treatment after volume resuscitation is achieved. In

patients responding to this therapy, numerous studies

have provided convincing evidence of the positive

effects of catecholamines on both 1302 and VO21’0�

particularly in the presence of increased lactate blood

levels which reflect tissue hypoxia.57 However, it is

interesting to note that in these studies catecholamines

were given primarily to correct the failing systemic

hemodynamics, while their impact on thermogenesis

was ignored. This aspect may be important in patients

with critically low cardiac output states unresponsive

to catecholamine therapy, where the catecholamine-

induced increase in energy dissipation may further

reduce an already insufficient tissue oxygenation,

although no clinical data are presently available on

this point. In these conditions, the management of the

failing cardiovascular system should rely on other

therapeutic means.

Optimal levels of Do2 and �O2 in various diseases

commonly encountered in critically patients have not

yet been specffically established and our knowledge

still remains largely empirical. Further studies are

necessary to determine the clinical importance of the

thermogenic effect of catecholamines when these

agents are used in the management of patients with

low flow states.

CONCLUSION

Catecholamines influence resting body ‘�O2 and

metabolic rate via several direct and indirect mecha-

nisms of action. In normal subjects, their main effect

on energy metabolism is related to the stimulation of

tissue 02 consumption and heat production, a complex

thermogenic phenomenon due to direct beta-adrener-

gic stimulation. In the critically ill, catecholamines

may also influence body Vo2 secondary to their effects

on systemic hemodynamics. In patients with low

cardiac output syndromes or with acute diseases

characterized by an abnormal tissue 02 extraction

capacity, 02 consumption is directly dependent and

limited by 02 delivery; catecholamines may increase

body Vo2 via their favorable effect on both cardiac

output and 02 delivery. Finally, ifthey do not improve

cardiac output and systemic 02 delivery, they may

unfavorably alter the balance between tissue 02 deliv-

ery and consumption by their calorigenic action and

thereby further reduce an already insufficient tissue

oxygenation.

ACKNOWLEDGMENTS: The authors wish to thank Dr. M.Dusmet for his helpful comments and Mrs M. Hemsch andN. Artingstall for their technical assistance.

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DOI 10.1378/chest.100.6.1676 1991;100; 1676-1684Chest

R Chioléro, J P Flatt, J P Revelly and E Jéquiercritically ill patients.

Effects of catecholamines on oxygen consumption and oxygen delivery in

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