Download Nitroglycerin increases venous return but reduces CVP: a preload

Academiejaar 2013 – 2014
Nitroglycerin increases venous return but
reduces CVP: a preload paradox?
Ine WITTERS
Promotor: Prof. dr. Stefan De Hert
Co-promotor: dr. Stefaan Bouchez
Masterproef voorgedragen in de master in de specialistische geneeskunde
Anesthesie-Reanimatie
Academiejaar 2013 – 2014
Nitroglycerin increases venous return but
reduces CVP: a preload paradox?
Ine WITTERS
Promotor: Prof. dr. Stefan De Hert
Co-promotor: dr. Stefaan Bouchez
Masterproef voorgedragen in de master in de specialistische geneeskunde
Anesthesie-Reanimatie
De auteur en de promotor geven de toelating deze masterproef voor consultatie beschikbaar te stellen
en delen ervan te kopiëren voor persoonlijk gebruik. Elk ander gebruik valt onder de beperkingen van
het auteursrecht, in het bijzonder met betrekking tot de verplichting uitdrukkelijk de bron te vermelden
bij het aanhalen van resultaten uit deze masterproef.
Datum
(handtekening ASO)
(handtekening promotor)
Ine Witters
Prof.dr. Stefan De Hert
(Naam ASO)
(Naam promotor)
Voorwoord
Het hanteren van de cardiovasculaire dynamiek in peroperatieve en kritiek zieke patiënten
blijft in de klinische praktijk een evenwichtsoefening die soms moeilijk blijkt door nog deels
onopgehelderde fysiologische mechanismen. Maar de techniek staat niet stil en dit laat ons toe
verder onderzoek te voeren naar de mysteries van de lichaamscirculatie. Het blijft een
intrigerende materie die me boeit en bezighoudt.
Ik wil enkele mensen bedanken die me ondersteund hebben bij het opstellen van deze
masterproef. Vooreerst mijn co-promotor, dr. Stefaan Bouchez, die me het onderwerp
aanreikte. Door zijn interesse in het onderwerp enthousiasmeerde hij me. Hij onderzocht,
corrigeerde en vulde mijn werk aan. Hij spaarde tijd noch moeite om zijn expertise te delen
met mij en hielp me enorm ondanks mijn krappe tijdsschema.
Prof. dr. Stefan De Hert bedank ik om het promotorschap over mijn werk te willen
aanvaarden en mij vooruit te helpen middels zijn ruime kennis over wetenschappelijk werk.
Prof.dr. Patrick Wouters, diensthoofd Anesthesie-Reanimatie van UZ Gent, bedank ik om mij
vijf jaar te begeleiden, te evalueren, en bij te sturen tijdens mijn opleiding.
Mijn moeder en mijn vrienden hebben mijn pieken en dalen tijdens het opstellen van deze
masterproef van dichtbij meegemaakt. Ze ondersteunden me en stuwden me voort door hun
motivatie.
Table of contents
Abstract …………………………………………………………………………………..
1
Introduction ………………………………………………………………………………
2
Objective …………………………………………………………………………………
9
Methods ………………………………………………………………………………….
9
Results ……………………………………………………………………………………
10
Discussion ……………………………………………………………………………….
12
References ……………………………………………………………………………….
14
Nederlandse samenvatting ………………………………………………………………
15
Abstract
For many years, physicians have considered the heart as the principal actor in cardiovascular
physiology. In the twentieth century, Guyton elaborated the idea of the venous system as a
determining factor for cardiac output. The heart can only pump out that what it receives and
thus in steady state conditions, venous return equals cardiac output. Venous return is affected
by three elements: right atrial pressure, resistance to venous return and mean systemic filling
pressure. This last element can be used as a parameter for effective circulating blood volume.
The main problem with this parameter is that it cannot be easily measured in clinical practice,
but only in experimental stop-flow models. Based on the Guytonian concepts, a clinical
decision support system, the NavigatorTM, was developed. This device integrates data from
conventional monitoring devices and calculates new variables such as the mean systemic
filling pressure analogue (Pmsa) and global heart performance (Eh). We used the NavigatorTM
to study the haemodynamic effects of nitroglycerin in cardiac surgery patients. We found that
nitroglycerin has, next to its ability to lower central venous pressure and arterial blood
pressure, a beneficial effect on global heart performance. Furthermore, we found that changes
in cardiac output after nitroglycerin administration were correlated to the change in pressure
gradient for venous return (Pmsa-CVP).
1
Introduction
Circulatory instability may be experienced in patients for a variety of reasons such as
perioperative ischaemia, heart failure or the effects of a critical illness. The use of
hemodynamic monitoring underpins the evaluation of the unstable cardiovascular system. In
1970 Swan and Ganz introduced the flotation catheter for the measurement of the pulmonary
artery wedge pressure and the assessment of the preload of the heart 1. Since that time
clinicians have used the wedge pressure to evaluate patients’ volume status and to optimize
preload to improve cardiac output. It is reasoned that cardiac output ultimately depends on the
ejection of blood from the left ventricle and is based on the Frank-Starling relationship: the
better the filling of the left heart, the better cardiac output.
About one hundred years ago, Frank and Starling enunciated their “law of the heart”: the idea
that the more the left ventricle is filled in diastole, the greater the stroke volume of the
following systole. Control of the blood volume since that time has focussed on the ‘Starling’
idea of providing the heart with adequate preload or diastolic filling. If we consider the left
ventricular end-diastolic volume (LVEDV) as the traditional preload measure , it’s clear that
an increase in LVEDV could be caused by an increase in the blood volume, an increase in
afterload which reduces ventricular ejection or a decline in ventricular function. The LVEDV
and other preload measures do not measure the volume state of the body.
Another way of thinking about Starling’s law is to consider it the property of the heart to
cause the cardiac output to equilibrate with the venous return. Normally these two are in
equilibrium. If venous return increases, the inflow to the heart exceeds the outflow, the heart
fills causing a rise in stroke volume and cardiac output. This process continues until both
equilibrate. Control of the cardiac output is therefore about control of the venous return.
In the nineteenth century, Bayliss and Starling described the importance of the venous
circulation in their experiments with dogs. In the second half of the twentieth century, Arthur
Guyton further elaborated this new concept of cardiovascular physiology. According to
Guyton, the real role of the heart in regulating cardiac output is to lower right atrial pressure
and allow blood to drain back to the heart (venous return) so it can be pumped out again2. The
heart only pumps out the amount of blood it receives from the venous system. Only in heart
failure, the pump function becomes a limiting factor. Thus, in steady state, venous return
equals cardiac output. Guyton also suggested that the mean circulatory filling pressure was
2
the first measurable quantity that allows one to relate blood volume mathematically to control
of cardiac output and arterial blood pressure3.
Not seldom, it proves to be difficult to assess the intravascular volume status in an unstable
patient and hence, fluid resuscitation is walking a tightrope. We know that excessive fluid
loading can have detrimental effects on the patient, e.g. in acute lung injury4. Therefore, the
development of an accurate and readily usable parameter to evaluate intravascular volume
status remained a challenge for a long time.
Venous return:
When we assume that cardiac output is controlled by venous return, this means that various
factors of the peripheral circulation that affect flow of blood into the heart from the veins,
called the venous return, are the primary controllers.
Venous return is affected by three principal factors:
1. Right atrial pressure (Pra)
2. Resistance to venous return
3. Mean systemic filling pressure (Pmsf)
In clinical practice, we use the central venous pressure (CVP) as a surrogate for Pra.
The resistance to venous return is defined as the resistance encountered by the blood in
returning to the heart. It comes for the greater part from the veins (two thirds), and to a lesser
extent from the arterioles and small arteries (one third). A common cause of increase in
venous resistance is the venoconstriction in hypovolemia.
Venous return can only occur when there is a pressure gradient. The CVP produces a
backward force on the veins that impedes blood flow into the right atrium. Guyton showed in
his experiments that venous return diminishes with rising CVP. When CVP rises to equal Pmsf,
flow into the right atrium drops to zero (figure 1). There is also a plateau in venous return
when CVP falls below -4mm Hg. This is due to the collapse of the large veins entering the
chest.
3
Figure 1: Venous return curve. Redrawn from Guyton.
The slope of the venous return curve is reciprocal to the resistance to venous return.
Venous return can be calculated through the following formula:
VR =
in which VR is venous return, Pmsf is mean systemic filling pressure and RVR is resistance to
venous return.
dVR = Pmsf - CVP
where dVR is the pressure gradient of venous return2.
Mean systemic filling pressure:
The mean systemic filling pressure is the mean pressure in the entire systemic circulation and
does not depend on the operation of the heart. In humans this pressure is close to 7 mmHg. It
can be measured in the vessels when all circulation is stopped and both arterial and venous
pressures have reached equilibrium. This technique was used by Guyton during his
experiments in dogs, where he used total circulatory arrest with induced fibrillation to
measure Pmsf. Occasionally P msf is observed in the intensive care unit or the operating room,
following cessation of ventilation in the brain dead patient or with pacemaker failure. P msf is a
measure of effective intravascular volume and it depends on the stressed or “vesseldistending” pressure. Total intravascular volume consists of both the stressed and unstressed
4
volume. The unstressed volume (60-70% of the total blood volume) is the quantity of blood
volume that does not stretch the vessels and thus is not a part of pressure buildup. It acts as a
blood reservoir. Meanwhile, the stressed volume (30-40% of total blood volume) is the
volume that distends the elastic wall of the vessels and that is hemodynamically active. The
stressed volume can be enlarged when fluid is administered of when unstressed volume is
being recruited through vasopressors.
Although it seemed a promising parameter, Pmsf didn’t prove to be a readily measurable
variable. All experiments assessing Pmsf had been done in stop-flow conditions, and thus
impracticable in the clinical field. The non-complete determination of cardiovascular volume
status in patients continued to deliver difficulties in terms of adequately treating the critically
ill or perioperative patients.
Recently, Maas et al.5 developed a bedside method for determining the P msf. They selected
postcardiac surgery patients who were mechanically ventilated and performed 12-second
inspiratory hold maneuvers at different ventilator plateau pressures (5, 15, 25 and 35cm H 2O).
During these maneuvers they measured central venous pressure (as a surrogate for P ra), and
pulse contour cardiac output (and thus venous return, since cardiac output equals venous
return in steady state conditions). Hence, they could construct venous return curves and
determine Pmsf. Moreover, the derived parameters can also be calculated, namely resistance to
venous return, systemic compliance and stressed volume.
Despite being an elegant method to measure Pmsf, it excludes a great portion of patients
considering that far from all patients are sedated and fully mechanically ventilated.
Consequently, they also experimented with stop-flow conditions in the arm (assuming that the
arm is representative of the entire circulation, and that a stop-flow in the arm will soon (20-30
seconds) lead to a pressure approximating Pmsf) and demonstrated that the results of Parm and
Pmsf are interchangeable.
Eh:
Developed by Parkin6, the dimensionless variable Eh is a measure that can be used to describe
global heart performance. Eh is influenced by rate, rhythm, inotropic and lusotropic
determinants, in addition to mechanical factors (e.g. raised intrathoracic pressure, pericardial
tamponade).
5
Eh =
0 ≤ Eh ≤ 1
When CVP is equal to zero and Eh equals 1, the heart is working at maximum efficiency. As
Pra rises and both (Pmsf-CVP) and Eh are decreasing, venous return and cardiac output will fall
accordingly.
Measures of resistance:
The third element to control in circulation after volume and the heart is resistance. Resistance
is the impediment the blood flow encounters in a vessel, but it cannot be measured by any
direct means. Instead, resistance must be calculated from measurements of blood flow and
pressure. Resistance is expressed as peripheral resistance unit (PRU) or as dyne sec/cm5. In
the systemic circulation, about two thirds of the total systemic resistance is arteriolar
resistance in the small arterioles. The resistance to venous return can be explained as the
resistance encountered by the blood in the return to the heart and depends upon the
distribution of the circulatory compliance. Resistance to venous return is affected by both
arterial and venous resistances. For example, a fall in arterial resistance decreases blood
pressure and increases cardiac output while a fall in venous resistance increases both cardiac
output and blood pressure. Changes in the venous component of resistance are not easily
measurable. It is the arteriolar resistance, quantified as the systemic vascular resistance, that is
usually the object of therapeutic vasoactive control. The arterial resistance and RVR are
predominantly influenced by tissue oxygenation and are prime determinants of the venous
return and cardiac output.
Navigator:
NavigatorTM (Applied Physiology Pty Ltd, Sydney Australia) is a clinical decision support
system that puts all these parameters together. The approach underpinning the Navigator®
monitoring system is to use an analogue for the mean systemic filling pressure and not any
preload measure like wedge pressure, to define the volume state. Together with central
venous pressure, this analogue for mean systemic filling pressure also permits a novel
definition of global heart performance E h. The device acquires raw data every five seconds
6
from connected monitors and graphs it on the monitor display. A touchscreen enables the
clinician to enter target ranges for blood pressure, cardiac output and oxygen delivery.
Patient’s age, height and weight are also required.
On the right hand side of the display are the current values of the connected monitors, targets
and the anthropometrical data of the patient. On the left hand side, the monitor displays the
patient’s position on x (resistance, SVR) and y (volumetric, P msa) axes. A vertical axis that
runs parallel to the Pmsa axis shows the value of the heart performance (E h). These two parallel
axes move independently from one another. The target zone is graphically delineated by
isoflow and isobar lines, defining a trapezoid zone in the center of the screen. The patient’s
current position is shown as a red dot in a yellow arrow. The direction of the arrow reflects
the suggested change in therapy in order for the patient position to reach the target zone.
Figure 2: Navigator display
NavigatorTM uses a software algorithm to calculate an analogue of Pmsf (Pmsa) using the
following equation, developed by Parkin6:
7
Pmsa = a x CVP + b x MAP + c x CO
where a is 0.96, b is 0.04 and c is a factor with the dimensions of resistance dependent on the
patient’s anthropometric data: c =
.
For example, in a patient that has a CVP of 0, MAP of 100, CO of 6 and c= 0.5, this means
that Pmsa = 0.96 x 0 + 0.04 x 100 + 0.5 x 6 = 7.
This equation was stipulated by Parkin in 1999 and he tested the clinical validity in patients
receiving continuous venovenous haemodiafiltration7.
Although Maas et al found in their study that there was a poor agreement between P msf and
Pmsa, they also stipulated that Pmsa is an effective parameter to detect changes in effective
circulating blood volume (full concordance between ΔP msf and ΔPmsa). They suggest a
calibration factor of 1.42 to adjust the Pmsa to match the Pmsf value8.
Cecconi et al. used the Navigator to assess the effects of a fluid challenge and fluid
responsiveness in intensive care patients. None of the parameters proved to be a good
predictor for fluid responsiveness, but they can distinguish the responders from the nonresponders. Pmsa increased in both fluid responders and non-responders, the CVP rises along
with Pmsa in non-responders. The change in Eh situated the patient on the Frank-Starling
curve: a decrease in Eh after fluid challenge showed that the heart was approaching the flat
part of the Frank-Starling curve and CVP rised correspondingly to limit venous return9.
Nitrates:
Nitrates and more specifically nitroglycerin (glyceryl trinitrate, GTN) are routinely used in
the treatment of heart failure, angina pectoris, acute treatment of hypertension and also in the
perioperative setting in patients undergoing cardiac surgery. It is known to have a significant
first-pass effect and necessitates parenteral (intravenous, sublingual) administration.
Denitration of nitroglycerine produces free nitrite (NO2-) which is converted to NO10. NO
then activates guanylate cyclase that catalyses the conversion of GTP to cyclic GMP, which
relaxes smooth muscle of the vasculature. It works through vasodilation with a preference
towards the venous capacitance vessels and the large and medium-sized coronary arteries. It
produces a reduction in ventricular filling pressures, systemic and pulmonary vascular
8
resistance and systemic arterial pressure. Nitroglycerin theoretically has more than one action.
Venous compliance will increase, while resistance to venous return will decrease. The arterial
tone will decrease depending on the dose and will cause a dose-dependent effect on mean
arterial pressure. The net effect will be a modest decrease in blood pressure and a variable
response in cardiac output depending on the state of the circulatory system when nitroglycerin
is administered.
Figure 3: Structure of glyceryl trinitrate (nitroglycerin)
Objective
In clinical practice, during cardiac surgery, cardiac output often increases. In order to explain
the physiological mechanism reponsible for the changes in cardiac output during the
administration of nitroglycerine in cardiac surgical patients, NavigatorTM was used. A feature
of the Navigator® is the ability to observe the influence of nitroglycerine on the circulatory
system using Pmsa and Eh in addition to the traditonal haemodynamic variables. The aim of the
study was to evaluate the circulatory effects of nitroglycerin in cardiac sugery patients
(coronary artery bypass graft patients).
Methods
The study was approved by the Ethics Committee of the University Hospital of Ghent.
Thirteen patients undergoing cardiac surgery, more particularly coronary artery bypass
surgery, were selected and included in the study. Written informed consent was obtained
before surgery. After induction of general anaesthesia and before surgical incision,
hemodynamic data were collected (standard monitoring, a radial artery catheter and cardiac
9
output by means of a Swan-Ganz catheter). Concurrently, data gathered by the NavigatorTM
device were noted. These data include P msa (analogue for mean systemic filling pressure), Eh
(heart performance) and SVR (systemic vascular resistance). Measurements were done in
supine position. Then nitroglycerin (NTG) infusion (0,5 mcg/kg/min) was started and after
hemodynamic stabilization (approximately after ten minutes), the same parameters were
collected and noted. Next, we compared the baseline hemodynamic data with those under
NTG administration. Data before and after administration of NTG were compared using
paired Student’s t test. The Pearson correlation test was calculated to assess the relation
between changes in the Pmsa-CVP gradient and the changes in CO.
Results
CVP decreased after the administration of GTN from 10 ± 3 to 6 ± 2 mm Hg (p = 0,001).
Figure 4: Central venous pressure at baseline and with nitroglycerin administration
Cardiac output did not change significantly after nitroglycerin infusion.
10
Figure 5: Cardiac output at baseline and with nitroglycerin administration
Systemic vascular resistance (SVR) decreased from 1397 ± 388 to 1181 ± 286 dyne.sec/cm5.
This was not significant (p = 4,1).
Figure 6 Systemic vascular resistance at baseline and with nitroglycerin infusion
Mean arterial blood pressure dropped from 80 ± 14 mm Hg to 62 ± 8 mm Hg (p = 0,016).
Pmsa decreased from 15,8 ± 2,8 mm Hg to 11,2 ± 2,0 mm Hg (p < 0,001). At the same time Eh
increased from 0.39 ± 0.10 to 0.50 ± 0.10 (p = 0.001).
There was a positive correlation between the change in gradient Pmsa - CVP (the driving
pressure for venous return) and the change in cardiac output (Figure).
11
Figure 7: ΔPmsa-CVP versus ΔCO. ΔPmsa-CVP = the change in gradient between Pmsa-CVP (baseline-GTN) and ΔCO = the
change in CO (baseline-GTN).
Discussion
An essential step in forming a consistent numerical relationship between measured data and
therapy is to resolve measured circulatory variables such as cardiac output, MAP and CVP
into volume, resistive and cardiac states. The use of P msa in cardiovascular physiology
provides the true object of control of volume therapy and the parameter E h provides a measure
of global performance of the heart and illustrates how VR regulates CO.
In our study we’ve noticed first of all a decrease in MAP, caused by a decrease in arterial tone
during the administration of GTN. Also Pmsa and CVP decreased as GTN increased the
venous compliance and decreased venous resistance.
Interestingly, we found that with the administration of GTN there was a better heart
performance as illustrated by an increase in Eh.
Changes in venous return and cardiac output after GTN infusion were not related to the
change in CVP but to the change in gradient between Pmsa and the CVP, the driving pressure
for venous return. The functional role of the heart may be seen as emptying the right atrium as
it is filled by the venous return, thus keeping the CVP well below P msf and maintaining
venous return. Changing this gradient will impact venous return and at the same time cardiac
output.
12
The reduction of CVP by nitroglycerin does not always implement a decrease in cardiac
output. The driving pressure of cardiac output depends on the gradient between Pmsf and CVP
and a rise in this gradient causes an increase in venous return (paradoxical). In our selected
group of patients, this phenomenon appears in several cases.
The development of new haemodynamic monitoring devices such as NavigatorTM, which
applies the Guytonian concepts of the circulation, can help us to understand the
cardiovascular dynamics of patients in a more detailed manner and can lead to more
appropriate clinical decision making. If this will also result in better outcome for the patient,
has yet to be determined. But aside from allowing us to better understand the patient’s
physiology, it can also help us to further explore in depth the hemodynamic effects of
cardiovascular medication e.g. nitroglycerin.
13
References:
1. Swan HJ, Ganz W, Forrester J, et al. Catheterization of the heart in man with use of a
flow-directed balloon-tipped catheter. N Engl J Med 1970; 283:447–51.
2. Guyton AC, Coleman TG, Granger HJ: Circulation: overall regulation. Annu. Rev.
Physiol. 1972; 34:13–46, 1972.
3. Hall JE, Guyton AC. Textbook of Medical Physiology. Twelfth edition. Saunders
Elsevier, 2011.
4. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B
et al. Comparison of two fluid-management strategies in acute lung injuries. N Engl J
Med 2006; 354:2564-2575.
5. Maas JJ, Geerts BF, van den Berg PC et al. Assessment of venous return curve and
mean systemic filling pressure in postoperative cardiac surgery patients. Crit Care
Med 2009; 37:912-918.
6. Parkin WG, Leaning MS. Therapeutic control of the circulation. J Clin Monit Comput
2008; 22:391-400.
7. Parkin WG, Wright C, Bellomo R, Boyce N. Use of a mean systemic filling pressure
analogue during the closed-loop control of fluid replacement in continuous
hemodiafiltration. J Crit Care 1994; 9:124-133.
8. Maas JJ, Pinsky MR, Geerts BF, de Wilde RB, Jansen JR. Estimation of mean
systemic filling pressure in postoperative cardiac sugery patients with three methods.
Intensive Care Med 2012; 38(9):1452-1460.
9. Cecconi M, Aya HD, Geisen M, Ebm C, Fletcher N, Grounds RM, Rhodes A.
Changes in the mean systemic filling pressure during a fluid challenge in postsurgical
intensive care patients. Intensive Care Med 2013; 39:1299-1305.
10. Valchanov KP, Arrowsmith JE. The role of venodilators in the perioperative
management of heart failure. Eur J Anaesth 2012: 29:121-127.
14
Nederlandse samenvatting
Het is een moeilijk evenwicht om bij een hemodynamisch instabiele patient een treffende
inschatting te maken van de cardiovasculaire status omdat courante parameters zoals
bloeddruk en cardiac output geen exact idee geven over de hartfunctie en/of intravasculair
circulerend bloedvolume. Daarnaast bestaat al eeuwen het idee dat het hart het centrum van de
cardiovasculaire fysiologie is, terwijl het perifere en dan voornamelijk veneuze partim van de
circulatie lang verwaarloosd werd. In de tweede helft van de 20ste eeuw werkte Guyton de
experimenten van Bayliss en Starr verder uit en poneerde hij de stelling dat de cardiac output
in normale omstandigheden volledig bepaald wordt door de veneuze terugkeer. Enkel bij
hartfalen wordt het hart een limiterende factor voor cardiac output. De veneuze retour wordt
door drie elementen bepaald: rechter-atriumdruk, weerstand tegen veneuze retour, en
gemiddelde systemische vullingsdruk. Deze laatste is een parameter die gebruikt kan worden
als maat voor effectief circulerend bloedvolume. Hoewel dit een interessante parameter is om
te gebruiken in de klinische setting, bleek deze in de praktijk moeilijk meetbaar. Enkel
wanneer de circulatie tijdelijk werd gestopt (vb. inductie van ventrikelfibrillatie bij het testen
van ICD-toestellen), equilibreerde het vaatstelsel zich tot de gemiddelde systemische
vullingsdruk. Recent echter ontwikkelde een onderzoeksgroep een methode om deze druk te
meten bij geventileerde patiënten. Daarnaast werd een apparaat ontwikkeld op basis van de
berekeningen en formules van Parkin, de Navigator TM, dat de data van de huidige monitoring
(arteriële bloeddruk, cardiac output, antropometrische gegevens) gebruikt en deze integreert
om een analoog te berekenen van de gemiddelde systemische vullingsdruk en ook een nieuwe
parameter introduceert, nl. de globale hartperformantie.
Wij gebruikten de NavigatorTM bij cardiochirurgische patiënten om uit te zoeken wat het
effect van nitroglycerine-toediening is op de cardiovasculaire parameters van de patiënt.
Hiervoor selecteerden we 13 patiënten waarvan we de baseline parameters noteerden en
daarna onderzochten we in welke mate deze parameters veranderden bij een toediening van
0,5 mcg/kg/min.
We stelden vast dat de toediening van nitroglycerine bij onze patiënten leidde tot een
verhoogde globale hartperformantie. Daarnaast stelden we ook vast dat er een correlatie
bestaat tussen het verschil in cardiac output (zonder en met nitroglycerine) en het verschil in
de drukgradiënt tussen de gemiddelde systemische vullingsdruk en de centraal veneuze druk
(de aandrijvingsdruk voor veneuze retour).
15