Sunteți pe pagina 1din 15

A Large B

Veins/Vena Cava elastance = P/V = slope

compliance (C) = 1/slope

= V2 - V1/P
= Vt - Vo/P
Atrium C = Vs/P
Venous (PRA)
Vo 0 V1 V2

Unstressed Volume Stressed Volume

(Vo) (Vs)
Total Intravascular Volume

Pms - PRA VR
VR = slope = Pms
Rv Pms - PRA
Pms - PRA 1 = Pms - PRA Rv
so Rv =
VR slope VR
Venous Rv = 1/slope Venous
Return slope = 1/Rv Return


0 0
Right Atrial Pressure (PRA ) Right Atrial Pressure


Cardiac cardiac
normal compliance


0 Right Atrial Pressure

Concise De nitive Review
Series Editor, Jonathan E. Sevransky, M D, M HS

Role of the Venous Return in Critical Illness and

Shock: Part IIShock and Mechanical Ventilation
Duane J. Funk, MD1,2; Eric Jacobsohn, MD1,2; Anand Kumar, MD1,3

To provide a conceptual and clinical review of the phys- various shock states including hypovolemic, cardiogenic, obstructive,
iology of the venous system as it is related to cardiac function in and septic shock. In particular, we demonstrate how these shock
health and disease. states perturb venous return/right heart interactions. We also show
An integration of venous and cardiac physiology under nor- how compensatory mechanisms and therapeutic interventions can
mal conditions, critical illness, and resuscitation. tend to return venous return and cardiac output to appropriate values.
The usual clinical teaching of cardiac physiology focuses An improved understanding of the role of the venous
on left ventricular pathophysiology and pathology. Due to the wide ar- system in pathophysiologic conditions will allow intensivists to
ray of shock states dealt with by intensivists, an integrated approach better appreciate the complex circulatory physiology of shock
that takes into account the function of the venous system and its inter- and related therapies. This should enable improved hemodynamic
action with the right heart may be more useful. In part II of this two-part management of this disorder. (Crit Care Med 2013; 41:573579)
review, we describe the physiology of venous return and its interaction cardiogenic shock; cardiovascular physiology; hemo-
with the right heart function as it relates to mechanical ventilation and dynamics; hemorrhagic shock; obstructive shock; septic shock

any, if not most, clinicians approach the management and treat the common hemodynamic problems encountered
of acute cardiovascular dysfunction and shock in critical care. The key concepts described here are covered in
using an analysis that emphasizes left ventricular detail in the rst part of the review. The reader is encouraged
physiology, probably as a consequence of medical training to read that earlier physiologic review before proceeding with
that emphasizes the role of left ventricular dysfunction in this current pathophysiologic review.
ischemic heart disease, the most common cause of death in To review, only a portion of the total blood volume (Vt )
the developed world. Intensivists deal with a broader array of contributes to the pressures generated in the circulation (1
cardiovascular perturbations including shock states in which 6). The unstressed intravascular volume (Vo) can be defined
vascular dysfunction and other extracardiac perturbations as that volume required to fill the circulatory system to
may dominate the clinical picture (e.g., septic, hypovolemic, capacity without any increase in cardiovascular transmural
or obstructive shock). In the rst part of this two-part review, pressure. Stressed volume (Vs) would be that amount
we reviewed an approach to cardiovascular physiology that which, when added to the unstressed volume, generates the
incorporates both cardiac and vascular elements that may be cardiovascular transmural pressure. Passive exsanguination
more useful to intensivists than one that focuses exclusively on of an anticoagulated experimental animal would result in a
left ventricular physiology. In the second part of this review, we large blood loss. The external, exsanguinated volume would
describe various shock states and how the knowledge of venous represent the Vs. The amount remaining in the circulation
return (VR) and cardiac output (CO) curves help to diagnose would be Vo.
The mean systemic pressure (Pms) is the average pressure
Section of Critical Care Medicine, Department of Medicine, University of throughout the entire circulatory system (cardiac/arterial/cap-
Manitoba, Manitoba, Canada.
illary/venous). It is most easily measured when pressures are
Department of Anesthesiology and Perioperative Medicine, University of
Manitoba, Manitoba, Canada. equilibrated during brief cardiac standstill (2, 7). During ac-
Section of Critical Care Medicine, Cooper University Hospital, Cooper tive circulation, the portion of the cardiovascular circuit that
Medical School of Rowan University, Camden, NJ. has a pressure equivalent to Pms is found in the small veins/
The authors have not disclosed any potential con icts of interest venules in the splanchnic bed. Pms can therefore be considered
For information regarding this article, E-mail: the upstream pressure driving VR (VR = Pms PRA/RV, where
Copyright 2013 by the Society of Critical Care Medicine and Lippincott PRA is right atrial pressure and RV is venous resistance). Another
Williams & Wilkins salient point is that the RV is represented by the inverse of the
DOI: 10.1097/ CCM .0b013e31827bfc25 slope of the VR curve in the graphics attached to this article.

Critical Care Medicine 573

VR AND CO IN PATHOPHYSIOLOGIC STATES transfers (on the order of hundreds of milliliters of uid) take
6 to 12 hrs and peak responses (> 0.5 L) occur within about 3
days depending on the blood volume loss (10, 11). If the hy-
The changes in cardiac function and VR curves during hypo- povolemia remains uncorrected, these compensatory changes
volemia and hypovolemic shock are shown in Figure 1. The would result in the shift of Vs, Vt, Pms, and the VR curve back
normal circulatory state is represented by point A on the graph toward normal over hours and days (shown in Fig. 1 as the
where the cardiac function (describing CO over a range of right shift from point B back to point C). The second compensatory
atrial pressures) and VR curves (describing VR over the same mechanism that occurs in hypovolemia is the secretion of en-
right atrial pressure range) intersect. With the acute onset of dogenous catecholamines. This results in an early upward and
hypovolemia, total volume (Vt) and stressed volume decrease, leftward shift of the ventricular function curve (shown in Fig. 1
mean systemic pressure (Pms) decreases, and the VR curve is as the change from point C to D). This allows for maintenance
shifted to the left (8). Consequently, it intersects the CO curve of near-normal CO with moderate degrees (< 15% total vol-
at a lower point and the net result is a decrease in VR/CO ume) of blood loss.
(point A to B). Note that this shift from point A to B does not The obvious treatment of hypovolemia is the restoration
take into account a sympathetic/endogenous catecholamine- of adequate Pms by the administration of intravenous uids,
driven compensatory increase in cardiac contractility (i.e., the initially in the form of crystalloid. In Figure 1, this can be
slope of the ventricular function curve remains unchanged) represented by the same shift on the curve from point B to
or venous resistance (i.e., the slope of the VR curve remains C (which also represents the response to compensatory uid
constant). shifts mentioned previously). Because Vt and Vs are increased,
A variety of compensatory responses that maintain CO/ Pms is partially restored, and the resultant CO/VR can be high-
VR must then be considered. First, Pms is supported through er than baseline (Fig. 1, point C to D) due to the endogenous
several mechanisms. Endogenous catecholamines from both catecholamine-induced increase in cardiac contractility. This
sympathetic nerves and the adrenal medulla cause an early therapy also has the immediate effect of decreasing RV due to
constriction of venous capacitance vessels with a resultant an improvement in red blood cell rheology/ uid viscosity with
shift of intravascular volume from unstressed volume (Vo) to hemodilution (because hemoglobin level is the primary deter-
stressed volume Vs (6). In addition, a slow shift of interstitial minant of blood viscosity). Later, RV may also be decreased as
uid into the vascular compartment occurs. As a consequence a consequence of vasodilatation due to circulating mediators
of an increase in precapillary resistance and a decrease in post- and NO (1214). These effects can cause a shift of the restored
capillary resistance with an enhanced production of plasma VR curve to a steeper slope and an increase in CO/VR (Fig. 1,
oncotic proteins under physiologic stress, a transfer of uids point D to E). The steeper ventricular function curve associated
from the interstitial to the intravascular compartment occurs with catecholamine stimulation and the decrease in resistance
(9). This results in a partial correction of Vt and Vs. Although to VR (Rv) with hemodilution explain why CO/VR can be in-
both processes begin immediately, clinically signi cant volume creased above the baseline with small or moderate (typically <
15% total blood volume) degrees of hemorrhage treated with
uid resuscitation.
As noted previously, the transfer of blood from Vo to Vs in
moderate hypovolemia can result in the maintenance of near-
normal CO and mean arterial pressure (MAP). The reserve of
the patient, however, is substantially decreased, and further
signi cant losses of intravascular volume may result in a sub-
stantial decrease in VR/CO and MAP. This is clearly demon-
strated when trauma patients are anesthetized. In addition to
their adverse effects on myocardial contractility, almost all the
anesthetic induction agents cause a signi cant increase in ve-
nous capacitance (i.e., a decrease in the proportion of Vs to Vo,
in relation to a xed Vt ). In hypovolemic patients, this can lead
to profound depression of VR/CO and MAP with a high risk
of death.
Often, clinicians treating a hypovolemic, hypotensive pa-
tient will administer vasopressors to maintain normal blood
pressure while there is ongoing uid resuscitation. Depending
Figure 1. Hypovolemia and hypovolemic shock. Arrows indicate increase on the choice of vasopressor, this may actually have a detrimen-
or decrease in parameter as appropriate (see text for explanation). Note tal effect on CO. The administration of a pure -agonist such as
that all gures in this review are illustrative and drawn to optimally dem- phenylephrine will generate a shallower slope of the VR curve,
onstrate the key concepts. In particular, they are not meant to imply an
absence of a plateau in the cardiac function curve with increasing lling and result in a decrease in CO, but with maintenance of near-
pressures. Pms = mean systemic pressure; Vt = total intravascular volume. normal blood pressure. This may be useful for brief periods to

574 February 2013 Volume 41 Number 2

maintain blood pressure in a range that allows effective auto- edema. If cardiac contractility is less severely depressed (with
regulation of ow to vital organs. a better maintained and steeper cardiac response curve), the
initial decrease in CO/VR will be less and the effect of mod-
Cardiogenic Shock est uid administration may be suf cient to restore it to a
There are a variety of etiologies that can cause cardiac failure normal range.
and cardiogenic shock. Most, including increased afterload, The use of inotropic agents is a standard therapy of cardiac
depression of myocardial contractility (ischemia, infarction, failure and cardiogenic shock of almost any etiology. The most
and others), arrhythmias, and mechanical valve failure affect common agents used are dobutamine, a synthetic catechol-
VR in similar ways in that they increase PRA. This decreases amine, and milrinone, a phosphodiesterase inhibitor. Both
the driving pressure gradient (PmsPRA) for venous ow and have similar effects on the cardiovascular system, generating a
reduces VR, which directly limits CO. moderate increase in cardiac contractility with a mild-to-mod-
As seen in Figure 2, cardiac failure and cardiogenic shock erate degree of arteriolar and venous vasodilatation (depen-
shift the cardiac function curve downward and to the right dent on a lower range dose in the case of dobutamine [1518]).
( atter curve) due to decreased contractility. The resulting in- Both effects are bene cial in cardiac failure. The increase in
tersection with the VR curve occurs at a lower than normal CO cardiac contractility and decrease in pulmonary vascular after-
(Fig. 2 point A to B). Note that at point B, Pms (the intercept of load generate a steeper Starling cardiac function curve. Used
the VR curve with the abscissa) is unchanged and although PRA alone without concomitant uids, a partial correction of a de-
is substantially higher than normal, VR/CO is markedly lower. pressed Starling curve will yield a signi cantly improved VR/
In Figure 2, PRA is the line drawn perpendicular from point B CO (Fig. 2, point B to D). However, assuming that Vs and Pms
to the abscissa of the graph. This is in contrast to the effect of are maintained or augmented with modest uid support, the
uid loading which increases Pms, VR/CO, and PRA. As noted intersection of the curves moves CO/VR upward toward nor-
earlier, the higher PRA reduces the gradient for blood ow to the mal even if contractility remains somewhat depressed (i.e., the
right atrium. Thus, despite a higher PRA and measured central ventricular response curve remains shifted downward com-
venous pressure in this condition, VR/CO is reduced. pared with normal) (Fig. 2, point D to E). In addition, the ve-
The compensatory release of endogenous catecholamines nous vasodilatory effect of both drugs will result in a decrease
causes an increase in Vs relative to Vo with a resulting increase in Rv (i.e., a steeper VR slope, not shown in Fig. 2), which will
in Pms (6). Administration of uid also increases Pms by increas- further augment CO/VR again, assuming that Vs and Pms are
ing Vt and Vs without a change in Vo. Both generate a similar maintained with uids as the natural effect of a vasodilator will
rightward shift of the VR curve (viscosity effects are ignored). be to decrease the proportion of Vs to Vo and decrease Pms.
However, because a large degree of myocardial dysfunction If cardiac injury is suf ciently severe, combined systolic
results in a ventricular function curve that is substantially and diastolic dysfunction shifts the ventricular response curve
attened, the bene cial impact of any increase in Pms from markedly downward ( atter) and to the right. This manifests as
uid administration or sympathetic activation will be modest a substantial increase in PRA that causes a narrowing of the Pms
(Fig. 2, point B to C). Further uid administration would not to PRA gradient. Because this gradient drives VR, decreased VR/
substantially increase CO, but would only increase pulmo- CO will manifest and, if suf ciently severe, cardiogenic shock
nary venous pressure and lead to the formation of pulmonary may result. In that circumstance, dopamine or norepinephrine,
inotropic agents with robust inotropic and vasoconstrictive ac-
tions, are often required. These drugs, in contrast to milrinone
and dobutamine, will tend to increase Vs as a portion of Vt . The
net effect is to generate a more modest inotropic effect than
dobutamine or milrinone while maintaining the robust vaso-
pressor effects required in hypotensive shock patients (19).
Although ischemic cardiac injury is dominantly left-sided,
such injury (from a myocardial infarction for example) will often
also cause right ventricular dysfunction. In addition to the fact
that there is often an element of direct RV injury with LV infarcts,
all causes of left ventricular dysfunction result in increases in
pulmonary artery pressures and RV afterload. This represents
an impediment to right ventricular systolic ejection and results
in a attening of the right heart Frank-Starling relationship.
In addition, the increased PRA associated with RV dysfunction
results in a narrowing of the VR gradient (Pms PRA) and a
decrease of VR/CO. As noted previously, in terms of venous
Figure 2. Cardiac failure and cardiogenic shock. Arrows indicate increase
or decrease in parameter as appropriate (see text for explanation). Pms = physiology, this increase in PRA is the only mechanism through
mean systemic pressure. which cardiac dysfunction can reduce VR.

Critical Care Medicine 575

Distributive Shock tal circulating volume (Vt) and stressed volume (Vs) may both
Distributive shock is a generic term for a pathophysiologic be decreased due to loss of uids to the interstitium, increased
state that combines hypotension with signi cant arteriolar insensible losses, and decreased oral intake. As a consequence
and venous dilation. Altered distribution of blood volume and of the decreased Pms in early, unresuscitated septic shock, VR,
blood ow is also characteristic. Septic shock is the prototypi- and CO are often reduced (Fig. 3, point A to B). Septic shock
cal disease that causes distributive shock, although the other is also associated with dilatation of large veins and shunting of
conditions found in critically ill patients may exhibit similar arterial blood ow to low resistance (fast time constant) vascu-
hemodynamic aberrations (systemic in ammatory response, lar beds (as described in part I of this review), both of which
anaphylactic/anaphylactoid responses, vasodilating drugs, liver decrease RV and augment VR (31, 32). Hemoconcentration due
failure, adrenal insuf ciency, anaphylaxis, thiamine de ciency, to increased uid loss to the interstitium, increased insensible
carcinoid syndrome, etc.). losses, and decreased uid intake may generate increased blood
Activation of the in ammatory cascade as a result of severe viscosity, attenuate the decrease in Rv, and limit augmentation
infection leads to the release of endogenous mediators such as of VR (30). Overall, despite hemoconcentration, RV decreases
cytokines (tumor necrosis factor-, interleukin-1, etc.), eico- and the slope of the VR curve becomes steeper (Fig. 3, point B
sanoids (prostacyclins, prostaglandins, leukotrienes), and oth- to C). However, the decreased Rv typically does not fully com-
ers (20, 21). Many of these factors drive up regulation of induc- pensate for the decreased Pms in unresuscitated septic shock,
ible nitric oxide synthase (NOS) producing nitric oxide, which and hence CO usually remains depressed. At this unresusci-
is thought to be the end mediator of vascular smooth muscle tated stage of septic shock, the physical examination frequently
relaxation throughout the cardiovascular system (2226). The is suggestive of a hypodynamic, low CO condition. The patient
result is a reduction of Rv and Pms. In addition, cytokine-me- will often be cold and clammy with a narrowed pulse pressure
diated NOS activity may have a substantial role in the variable (hypodynamic shock). Central and mixed venous oxygen satu-
degrees of myocardial depression that is typically seen in sepsis rations are often low at this stage (3335).
and septic shock (27, 28). A graphical representation of septic Subsequently, uid resuscitation in septic shock generates a
shock is depicted in Figure 3. marked augmentation in Vt . Although 5 to 10 L of crystalloid
Early in the course of septic shock, Pms decreases. One of the over 24 hrs is often provided in clinical practice (36, 37), a sig-
primary reasons is a shift of stressed volume (Vs) to unstressed ni cantly smaller volume on the order of 0.5 to 2 L is probably
volume (Vo) as a consequence of increased venous capacitance suf cient to suf ciently augment Vt (35, 38). Fluid resuscita-
resulting from active dilation of small venules/veins. This in- tion results in a correction of Vs and Pms back to normal (or
crease in unstressed volume (Vo) and decrease in stressed vol- potentially higher), allowing the decreased Rv (with steeper VR
ume (Vs) have been con rmed in experimental animal models curve) to be manifested by increased VR/CO (Fig. 3, point C
of canine and porcine endotoxemia (2931). Furthermore, to- to D) that can be more than double normal (31). The hyper-
dynamic circulation may be further accentuated by a further
decrease in RV related to hemodilution and decreased blood
viscosity (not shown in gure). This classical hyperdynamic
(high CO/low SVR) hemodynamic picture of established sep-
tic shock typically does not manifest without uid resuscita-
tion (3942). However, even a modest degree of uid resusci-
tation may be suf cient to allow the permissive effects of the
decreased Rv to be expressed as increased CO.
Based on echocardiography and radionuclide ventriculog-
raphy, the majority of patients with septic shock also develop
a degree of biventricular myocardial depression as manifested
by a decreased ejection fraction (with biventricular dilatation
(4345)). However, the decreased Rv in the context of restored Vs
due to uid resuscitation normally overshadows the depressed
contractility so that patients remain substantially hyperdynamic
with increased VR/CO. These effects are illustrated in Figure 3
(point D to E). In a small subset of patients, myocardial depres-
sion is suf ciently severe that VR/CO remains decreased even af-
ter resuscitation (Fig. 3, point F). In this situation, an emphasis
on inotropic support rather than the more typical vasopressor
approach to therapy may be required.

Obstructive Shock
Figure 3. Septic shock. Arrows indicate increase or decrease in param-
eter as appropriate. Circled N indicates normal (see text for explana- There are several pathophysiologic phenomena that cause
tion). Pms = mean systemic pressure; Rv = venous resistance. obstructive shock. Conditions such as tension pneumothorax,

576 February 2013 Volume 41 Number 2

pericardial tamponade, or compression of the inferior vena sure gradient. When PPL increases with a tension pneumotho-
cava secondary to abdominal compartment syndrome or preg- rax, the transmural pressure gradient narrows and ventricular
nancy can all cause a decrease in CO due to obstructive shock. lling is impaired. Ventricular lling can be maintained but at a
Large pulmonary emboli can also cause a form of obstructive signi cantly higher lling pressure (PRA). This effect shifts the
shock that acts very similarly to cardiogenic shock. Given its ventricular function curve to the right. In this situation, VR/
interesting and complex pathophysiology, tension pneumo- CO will transition from point A to B (rather than A1) as shown
thorax will be examined as an example of obstructive shock. in Figure 4.
Tension pneumothorax causes a reduction in the VR be- Several other hemodynamic pathophysiologic events occur.
cause of an increase in intrathoracic pressure. As we can see in The increase in PPL causes compression of the large veins in the
Figure 4, several changes occur in the VR and cardiac function thorax increasing Rv. The result is a shallower slope in the VR
curves with the development of a tension pneumothorax. curve, which further depresses VR/CO (Fig. 4, point B to C).In
The primary pathophysiologic event in the development of addition to the rightward shift of the cardiac function curve,
obstructive shock due to tension pneumothorax is that an in- the curve is attened as a consequence of a substantial increase
creasingly positive pleural pressure (PPL) and not PRA becomes in RV afterload secondary to lung collapse and acute hypox-
the limiting factor of blood ow to the right heart (46, 47). emia (which increases pulmonary vascular resistance) induced
When PPL exceeds PRA, the numerator of the VR equation (VR by the pneumothorax (47). This further reduces VR/CO (Fig.
= Pms PRA/Rv) becomes Pms PPL. VR no longer increases with 4, point C to D).
a decrease in PRA. Normally, VR plateaus as PRA approaches Patm . There are signi cant compensatory responses that are not
With tension pneumothorax, the limitation of VR occurs at PPL shown graphically in the interests of simplicity. Endogenous
(i.e., a value greater than Patm where PRA = 0). Assuming that catecholamine release results in a shift of Vo to Vs without an
Pms and Rv are unchanged, this results in a VR curve where the alteration in Vt resulting in an increase in Pms. This effect may
in ection of the plateau point is shifted downward and to the be partially offset by vasoconstriction of large veins and the
right (with a down-shifted plateau) but where the slope (1/Rv) vena cava resulting in a higher Rv and a shallower VR curve.
and the x-axis intercept (Pms) are unchanged. In the absence In addition, this stress-associated sympathetic catecholamine
of other effects, a physiologic impossibility would result; the surge will tend to increase contractility resulting in a steeper
Starling response curve although it will not offset the increase
intercept of the cardiac function curve and the VR curve (de-
in right ventricular afterload.
ning VR/CO) would shift to the plateau portion of the VR
Temporizing therapies may prove useful depending on the
curve with only a modest depression of VR/CO (Fig. 4, point A
degree of hemodynamic compromise. The rst therapy applied
to A1). This is not possible because there can be no ventricular
is often intravascular expansion with resuscitative uids, which
volume when intrathoracic pressure (re ected by PPL) exceeds
increases Vt, Vs, and Pms shifting the VR curve to the right so
intraventricular pressure (re ected by PRA) as occurs at this
that it intercepts the cardiac contractility curve at a somewhat
theoretical point.
higher CO/VR (Fig. 4, point D to E). This may be effective if
However, as part of the response to increased PPL, the cardiac
the pneumothorax is associated with only a modest increase in
function curve is shifted rightward on the graph. This rightward
PPL. However, the administration of large amounts of uid will
shift occurs as a consequence of the fact that the presence of an result in a negligible increase in VR/CO despite substantial in-
increased pleural pressure adversely impacts effective cardiac creases in Pms if the cardiac function curve is markedly attened
compliance. Diastolic ventricular distension (preload) and the by the increased right ventricular afterload. If uid administra-
Starling response are dependent on the cardiac transmural pres- tion results in an insuf cient response, an inotropic agent is of-
ten initiated. The combination of uids and inotropic support
may be more effective than either therapy alone (Fig. 4 point E
to F). However, despite such aggressive cardiovascular support,
CO/VR rarely achieves normal values except in the early stages
of hemodynamic compromise. In addition, uid therapy is lim-
ited by the increase in capillary ltration that will occur with
the increase in hydrostatic pressure from administering exces-
sive volume. Further in the pathophysiologic progression of this
condition, supportive modalities are unable to shift the curves
suf ciently and only decompression will be effective.
If the hypotension that is often seen with a tension pneumo-
thorax is treated with a pure vasopressor (such as phenyleph-
rine), the result will be a further decrease in CO/VR because
of the increase in RV and, potentially, increase in pulmonary
Figure 4. Tension pneumothorax as an example of obstructive shock. afterload.
Arrows indicate increase or decrease in parameter as appropriate
(see text for explanation). Pms = mean systemic pressure; Rv = venous When pericardial tamponade is the cause of obstructive
resistance; Vs = stressed volume. shock, the same physiologic principles as in tension pneumo-

Critical Care Medicine 577

thorax apply. The difference being that the impedance to VR is ingly, in drawing a line perpendicular from point C to the
now pericardial pressure (PPer) as opposed to PPL and the nu- abscissa/x-axis of the VR graph (the intersection represent-
merator for the VR equation becomes Pms PPer. As with ten- ing PRA) and a similar line from point A to the abscissa, it is
sion pneumothorax, the initial use of uids and inotropes will apparent that under positive pressure ventilation PRA actually
have modest effects on improving CO but with pathophysi- increases despite a decrease in CO/VR. This is part of the rea-
ologic progression, only decompression of the tamponade will son why static predictors of preload such as PRA are inadequate
be effective. in predicting CO and volume responsiveness in mechanically
ventilated patients (4853).
Effect of Positive Pressure Ventilation on VR and
Cardiac Function
The effects of mechanical ventilation on cardiac function and
The understanding of circulatory physiology is paramount
VR are similar in nature to tension pneumothorax, but gener-
to the treatment of the critically ill. The traditional approach
ally less in magnitude. As seen in Figure 5, institution of posi-
has been to focus on the left heart and the factors that govern
tive pressure mechanical ventilation causes analogous changes
left heart CO. As the reader has seen, there are many forms of
(when compared with tension pneumothorax) in the VR and
shock that involve alterations in the vasculature or other extra-
cardiac function curves that can, on occasion (and depend-
cardiac perturbations. It is in these cases that the concept of VR
ing on cardiac function and volume status), result in hypo- plays an important role in the understanding and treatment of
tension. Upon switching from negative pressure ventilation to these complex patients.
positive pressure ventilation, RV increases (a shallower slope of The initial description of the role of the vasculature in regu-
the VR curve) because of the compression of the intrathoracic lating CO over 115 yr ago by Bayliss and Starling and further
veins and vena cava. The result is the shift from point A to delineated by Guyton in the 1950s still has clinical relevance
B in Figure 5. In addition, mean positive intrathoracic pres- today when managing patients with complex pathophysiology.
sure caused by mechanical ventilation results in a rightward
shift of the right heart ventricular function curve as a conse-
quence of decreased effective cardiac compliance. The curve is REFERENCES
1. Greenway CV, Lister G E: Capacitance effects and blood reservoir
also somewhat depressed/ attened due to the increased right function in the splanchnic vascular bed during non-hypotensive haem-
ventricular afterload due to increases in pulmonary vascular orrhage and blood volume expansion in anaesthetized cats. J Physiol
(Lond) 1974; 237:279294
resistance caused by the positive intrathoracic pressure (Fig.
2. Guyton AC: Determination of cardiac output by equating venous
5, point B to C). return curves with cardiac response curves. Physiol Rev 1955;
Although endogenous catecholamine release will reverse 35:123129
some of these changes, the standard therapy of uid infu- 3. Hainsworth R: Vascular capacitance: Its control and importance. Rev
sion is often needed to return CO/VR to normal range (Fig. 5, Physiol Biochem Pharmacol 1986; 105:101173
4. Milnor W: Cardiovascular Physiology. New York, Oxford University
point C to D). However, CO/VR compromise may be especially Press, 1990
profound if the patient is already volume depleted with a low 5. Noble BJ, Drinkhill MJ, Myers DS, et al: Mechanisms responsible for
Pms (Fig. 5, point C to E) or if intrathoracic pressure is mark- changes in abdominal vascular volume during sympathetic nerve stim-
edly increased (high levels of positive end-expiratory pressure ulation in anaesthetized dogs. Exp Physiol 1997; 82:925934
[PEEP] or auto PEEP in association with chronic obstructive 6. Rothe CF: Re ex control of veins and vascular capacitance. Physiol
Rev 1983; 63:12811342
pulmonary disease/asthma) which results in both an increase 7. Magder S, De Varennes B: Clinical death and the measurement of
in RV (not shown) and more profound shift and depression stressed vascular volume. Crit Care Med 1998; 26:10611064
of the cardiac function curve (Fig. 5, point C to F). Interest- 8. Holcroft JW: Impairment of venous return in hemorrhagic shock. Surg
Clin North Am 1982; 62:1729
9. Keele C, Samson N: Wrights Applied Physiology. 11th Edition. Ox-
ford Medical Publications, Oxford University Press, 1965
10. Angele MK, Schneider CP, Chaudry IH: Bench-to-bedside review:
Latest results in hemorrhagic shock. Crit Care 2008; 12:218
11. Peitzman AB, Billiar TR, Harbrecht BG, et al: Hemorrhagic shock.
Curr Probl Surg 1995; 32:9251002
12. Md S, Moochhala SM, Siew-Yang KL: The role of inducible nitric oxide
synthase inhibitor on the arteriolar hyporesponsiveness in hemorrhag-
ic-shocked rats. Life Sci 2003; 73:18251834
13. Thiemermann C, Szab C, Mitchell JA, et al: Vascular hyporeactivity to
vasoconstrictor agents and hemodynamic decompensation in hemor-
rhagic shock is mediated by nitric oxide. Proc Natl Acad Sci USA
1993; 90:267271
14. Zingarelli B, Caputi AP, Di Rosa M: Dexamethasone prevents vascular
failure mediated by nitric oxide in hemorrhagic shock. Shock 1994;
Figure 5. Effect of mechanical ventilation. Arrows indicate increase or 15. Lehtonen LA, Antila S, Pentikinen PJ: Pharmacokinetics and phar-
decrease in parameter as appropriate (see text for explanation). Pms = macodynamics of intravenous inotropic agents. Clin Pharmacokinet
mean systemic pressure; Rv = venous resistance; Vs = stressed volume. 2004; 43:187203

578 February 2013 Volume 41 Number 2

16. Petersen JW, Felker G M: Inotropes in the management of acute heart 36. Finfer S, Bellomo R, Boyce N, et al; SAFE Study Investigators: A com-
failure. Crit Care Med 2008; 36(1 Suppl):S106S111 parison of albumin and saline for uid resuscitation in the intensive
17. Geerts BF, Maas JJ, Aarts LP, et al: Partitioning the resistances along care unit. N Engl J Med 2004; 350:22472256
the vascular tree: Effects of dobutamine and hypovolemia in piglets 37. Rackow EC, Kaufman BS, Falk JL, et al: Hemodynamic response to
with an intact circulation. J Clin Monit Comput 2010; 24:377384 uid repletion in patients with septic shock: Evidence for early depres-
18. Ogilvie RI: Effects of inotropic agents on arterial resistance and venous sion of cardiac performance. Circ Shock 1987; 22:1122
compliance in anesthetized dogs. Can J Physiol Pharmacol 1982; 38. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy
60:968976 Collaborative Group: Early goal-directed therapy in the treatment of
19. DiSesa VJ, Brown E, Mudge GH Jr, et al: Hemodynamic comparison of severe sepsis and septic shock. N Engl J Med 2001; 345:1368
dopamine and dobutamine in the postoperative volume-loaded, pres- 1377
sure-loaded, and normal ventricle. J Thorac Cardiovasc Surg 1982; 83: 39. Blain CM, Anderson TO, Pietras RJ, et al: Immediate hemodynamic
256263 effects of gram-negative vs gram-positive bacteremia in man. Arch
20. Annane D, Bellissant E, Cavaillon JM: Septic shock. Lancet 2005; Intern Med 1970; 126:260265
365:6378 40. Kumar A, Haery C, Parrillo JE: Myocardial dysfunction in septic shock:
21. Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, et al: The patho- Part I. Clinical manifestation of cardiovascular dysfunction. J Cardio-
genesis of sepsis. Annu Rev Pathol 2011; 6:1948 thorac Vasc Anesth 2001; 15:364376
22. Cauwels A: Nitric oxide in shock. Kidney Int 2007; 72:557565 41. MacLean LD, Mulligan WG, McLean AP, et al: Patterns of sep-
23. Cobb JP, Danner RL: Nitric oxide and septic shock. JAMA 1996; tic shock in manA detailed study of 56 patients. Ann Surg 1967;
275:11921196 166:543562
24. Kilbourn RG, Gross SS, Jubran A, et al: NG-methyl-L-arginine 42. Weil MH, Nishjima H: Cardiac output in bacterial shock. Am J Med
inhibits tumor necrosis factor-induced hypotension: Implications for 1978; 64:920922
the involvement of nitric oxide. Proc Natl Acad Sci USA 1990; 87: 43. Jardin F, Fourme T, Page B, et al: Persistent preload defect in severe
36293632 sepsis despite uid loading: A longitudinal echocardiographic study
25. Szabo C, Wu CC: Role of nitric oxide in the development of vas- in patients with septic shock. Chest 1999; 116:13541359
cular contractile dysfunction in circulatory shock. J Med Sci 2011; 44. Parker MM, McCarthy KE, Ognibene FP, et al: Right ventricular dys-
31:001016 function and dilatation, similar to left ventricular changes, character-
26. Titheradge MA: Nitric oxide in septic shock. Biochim Biophys Acta ize the cardiac depression of septic shock in humans. Chest 1990;
1999; 1411:437455 97:126131
27. Kumar A, Brar R, Wang P, et al: Role of nitric oxide and cGMP in hu- 45. Parker MM, Shelhamer JH, Bacharach SL, et al: Profound but revers-
man septic serum-induced depression of cardiac myocyte contractil- ible myocardial depression in patients with septic shock. Ann Intern
ity. Am J Physiol 1999; 276(1 Pt 2):R265R276 Med 1984; 100:483490
28. Kumar A, Thota V, Dee L, et al: Tumor necrosis factor alpha and in- 46. Jacobsohn E, Chorn R, OConnor M: The role of the vasculature in
terleukin 1beta are responsible for in vitro myocardial cell depression regulating venous return and cardiac output: Historical and graphical
induced by human septic shock serum. J Exp Med 1996; 183:949 approach. Can J Anaesth 1997; 44:849867
958 47. Luecke T, Pelosi P, Quintel M: [Haemodynamic effects of mechanical
29. Bressack MA, Morton NS, Hortop J: Group B streptococcal sepsis in ventilation]. Anaesthesist 2007; 56:12421251
the piglet: Effects of uid therapy on venous return, organ edema, and 48. Marik PE, Baram M, Vahid B: Does central venous pressure predict
organ blood ow. Circ Res 1987; 61:659669 uid responsiveness? A systematic review of the literature and the
30. Hiesmayr M, Jansen JR, Versprille A: Effects of endotoxin infusion on tale of seven mares. Chest 2008; 134:172178
mean systemic lling pressure and ow resistance to venous return. 49. Kumar A, Anel R, Bunnell E, et al: Pulmonary artery occlusion pres-
P ugers Arch 1996; 431:741747 sure and central venous pressure fail to predict ventricular lling
31. Magder S, Vanelli G: Circuit factors in the high cardiac output of sep- volume, cardiac performance, or the response to volume infusion in
sis. J Crit Care 1996; 11:155166 normal subjects. Crit Care Med 2004; 32:691699
32. Madger S: Shock physiology. In: Pathophysiologic Foundations of 50. Kntscher MV, Germann G, Hartmann B: Correlations between car-
Critical Care. Pinsky MR, Vincent JF (Eds). Baltimore, MD: Williams diac output, stroke volume, central venous pressure, intra-abdominal
and Wilkins, 1993, pp 140160 pressure and total circulating blood volume in resuscitation of major
33. Pope JV, Jones AE, Gaieski DF, et al; Emergency Medicine Shock burns. Resuscitation 2006; 70:3743
Research Network (EMShockNet) Investigators: Multicenter study of 51. Marik PE, Monnet X, Teboul JL: Hemodynamic parameters to guide
central venous oxygen saturation (ScvO(2)) as a predictor of mortality uid therapy. Ann Intensive Care 2011; 1:1
in patients with sepsis. Ann Emerg Med 2010; 55:4046.e1 52. Michard F, Chemla D, Richard C, et al: Clinical use of respiratory
34. Nguyen HB, Rivers EP, Knoblich BP, et al: Early lactate clearance is changes in arterial pulse pressure to monitor the hemodynamic ef-
associated with improved outcome in severe sepsis and septic shock. fects of PEEP. Am J Respir Crit Care Med 1999; 159:935939
Crit Care Med 2004; 32:16371642 53. Osman D, Ridel C, Ray P, et al: Cardiac lling pressures are not ap-
35. Donnino M, Nguyen HB, Rivers EP: A hemodynamic comparison of ear- propriate to predict hemodynamic response to volume challenge.
ly and late phase severe sepsis and septic shock. Chest 2002; 122:5S Crit Care Med 2007; 35:6468

Critical Care Medicine 579