Hemodynamic goal-directed therapy. A review.

2009·0.61 MB·English

by  Romagnoli, S

pprroocceeeeddiinnggss
Cardiovascinu Ilnatre Annseivset hCeasriea
rEViEw
54
hemodynamic goal-directed therapy.
A review
S. Romagnoli1, S.M. Romano2, S. Bevilacqua1, C. Lazzeri1, F. Ciappi1, D. Dini1,
C. Pratesi3, G.F. Gensini2
1Department of Cardiac and Vascular Anesthesia and Post-Surgical Intensive Care Unit, Careggi Hospital, Florence, Italy;
2Department of Critical Care Medicine and Surgery, University of Florence, Careggi Hospital, Florence, Italy;
3Department of Vascular Surgery, University of Florence, Careggi Hospital, Florence, Italy
AbStrAct
Patients can show arterial pressure and cardiac index within the normal range and still be in circulatory shock
if oxygen and metabolic demand is increased or blood flow distribution is altered.
Lactate is produced in anaerobic environment to preserve cellular integrity and physicians use its blood con-
centration value as a reliable marker of tissue hypoxia and energy failure.
The authors review the recent literature on the importance of mixed venous oxygen saturation (Svo) as an
2
early sign of inadequate Do that precede the lactate production.
2
Keywords: Lactate, Goal directed therapy, Low cardiac output syndrome, Sepsis.
Cardiac output (Co) is the primary deter- pAthophySiologicAl
minant of global oxygen transport from the implicAtionS
heart to the tissues since it represents the
main contributor to the oxygen delivery Inadequate hemodynamics had been con-
(Table 1). sidered for a long time a clinical condi-
Co calculation has been used as the main tion characterized by low arterial blood
parameter for hemodynamic monitoring pressure and/or flow. This concept could
since Swan and Ganz (1) introduced the be misleading if not related with that of
pulmonary artery catheter (PAC) in clini- oxygen demand and of blood flow distribu-
cal practice. tion to tissues. Therefore, one patient can
Physicians need to monitor hemodynam- show arterial pressure and cardiac index
ics of critically ill patients in order to op- (CI) within the normal range and still be in
timize pre-load, after-load, and contractil- circulatory shock if oxygen and metabolic
ity by titrating fluids, diuretics, inotropes, demand is increased or blood flow distribu-
and vasoactive drugs, as to achieve the best tion is altered. Studies by Shoemaker et al.
delivery of oxygen and metabolites to tis- (2), at the end of eighties, have focused on
sues. the observation that critically ill patients
who survived major surgery had higher
Do values than non-survivors. According
2
Corresponding author: to Shoemakers’ results a perioperative opti-
Dr. Stefano Romagnoli mization of Do up to supra-normal values,
Department of Heart and Vessels 2
Cardiac and Vascular Anesthesia and was accompanied with reduced complica-
Post-Surgical Intensive Care Unit tions, duration of hospitalization, intensive
Careggi Hospital
Viale Morgagni, 85 care unit (ICU) length of stay, mechanical
50134 florence, Italy
ventilation, and, therefore, overall costs.
E-mail: [email protected]
hemodynamic goal-directed therapy. A review
table 1 - Hemodynamic parameters. 55
hemodynamic parameter calculation Absolute range Size-Adjusted range*
Delivery of oxygen (Do) Co x (1.34 x Hb x Sao) 900-1100 ml/min 520-600 ml/min/m2
2 2
+ (0.003 x Pao) x 10
2
oxygen consumption (Vo) Co x (Cao - Cvo) x 10 200-270 ml/min 110-160 ml/min/m2
2 2 2
Pulse Pressure Variation PP -PP / <10-15%
max min
(PPV) % PP +PP /2x100
max min
Systolic Pressure Variation SP -SP / <10-15%
max min
(SPV) % SP +SP /2x100
max min
Stroke Volume Variation SV -SV / < 10-15%
max min
(SVV) % SV +SV /2x100
max min
Abbreviations: Co, Cardiac output (l/min); Hb, hemoglobin concentration (g/dl); Sao, oxygen saturation in arterial
2
blood; Pao, oxygen partial pressure in arterial blood (mmHg); Cao, arterial oxygen content ((1.34 x Hb x Sao) +
2 2 2
(0.003 x Pao)); Cvo, venous oxygen content ((1.34 x Hb x Svo) + (0.003 x Pvo)); PP, Pulse Pressure; SP, Systolic
2 2 2 2
Pressure; SV, Stroke Volume. *Size-adjusted values are the absolute values divided by the patient’s body surface area in
square meters (m2).
on the basis of these findings many inves- cycle and the electron transport chain can-
tigators had been considering that values of not proceed and the metabolic pathways
Co and Do , previously believed “in nor- shift toward the conversion of glucose
2
mal range”, could be inadequate to fulfill into pyruvate (net energy profit: 2 ATP).
the tissue oxygen needs. The conditio sine qua non the above men-
Deep modifications in the cellular meta- tioned reaction can occur is the presence of
bolic-energetic pathways occur when in- nAD+ (oxidized form of nADH) that is
adequate Do is delivered to tissues (e.g. produced when pyruvate is converted into
2
low Co states), whatever was the cause. lactate. Hence, lactate is produced in an-
Independently from cellular oxygen ten- aerobic environment as to preserve cellular
sion, in the cytoplasm, one mole of glucose integrity and, physicians, can use its blood
is transformed into 2 moles of pyruvate. concentration value as a reliable marker of
This reaction, needs 2 nAD+ molecules tissue hypoxia and energy failure (3). The
and results in the net production of 2 ATP metabolic shifting from a high energy pro-
and 2 nADH molecules for each molecule duction pathway, in presence of adequate
of glucose (poor energetic profit). If oxygen oxygen, to a poor but rescuing option in
availability is adequate, the pyruvate within anaerobic conditions helps, thanks to lac-
the mitochondrial matrix, is converted to tate, to maintain cellular vitality but, if pro-
acetyl-CoA and Co . Acetyl-CoA, by means longed over time, structural alterations of
2
of the citric acid cycle (or tricarboxylic acid mitochondria occur with consequent cellu-
cycle or Krebs cycle) is fully oxidized to Co lar death.
2
and H o, producing nADH that is oxidized Intensive care givers have learned that
2
by the electron transport chain (inner mi- when mixed venous oxygen saturation
tochondrial matrix) using oxygen as the ((Svo ) i.e. the oxygen saturation of blood
2
final electron acceptor leading to a strong sampled in the pulmonary artery (blood
free energy production (net energy profit: coming from both superior and inferior
36 moles ATP/mole glucose). vena cava)) drops under normal values
Conversely, when dysoxia occurs (anaero- (normal values >70%), Do is suspected
2
bic conditions, low Co states), the Krebs to be inadequate. Svo although very sen-
2
S. Romagnoli, et al.
56 sitive is a non-specific marker of low Co control group. In fact, GDT was decided on
because depends on several factors, other the basis of CI in one group and Svo in
2
than flow (Co), it depends on arterial satu- the other. otherwise from Shoemakers’ in-
ration (respiratory function), cells metabo- vestigation, this study did not come to simi-
lism, and hemoglobin concentration. When lar results and the authors concluded that
Do falls, the cell still maintains its needed “Hemodynamic therapy aimed at achieving
2
oxygen consumption (Vo ) by means of an supra-normal values for the cardiac index or
2
increase in oxygen uptake thus causing a normal values for mixed venous oxygen satu-
reduction of Svo . Therefore, Svo values ration does not reduce morbidity or mortality
2 2
under 70% can represent an early sign of among critically ill patients”.
inadequate Do that precede the lactate one of the main differences between the
2
production. studies by Gattinoni and Rivers is the
When the duration of dysoxia persists lon- TIME elapsed from the patient hospitaliza-
ger or if microcirculation disorders occur, tion and the inclusion in a hemodynamic
such as capillary shunts, preventing normal GDT group. In the Rivers’ study the median
distribution of blood to tissues, the Svo time from arrival at the emergency depart-
2
value can even return to normal values sug- ment to enrollment was only 50.5 minutes
gesting that mitochondria can’t uptake any (Standard Therapy Group) and 59 minutes
more oxygen. Since the duration of dysoxia (Early GDT Group) respectively. Moreover
is associated to the magnitude of cell injury, the median value of central venous oxygen
the earlier is the intervention, the greater is saturation ((ScVo ); saturation in oxygen
2
the physiological response to treatment and of blood sampled in the superior vena cava
the better is the outcome. or right atrium, considered in this study
as a surrogate of Svo ) in the patients of
2
Rivers’ study was almost 50%, a value that
purpoSE of hEmodynAmic strongly suggests a severe hemodynamic
monitoring impairment. The mean value of Svo in
2
the patients of Gattinoni’s study was only
In the study by Shoemaker et al. (2), a slightly lower than 70% (67.3±10.5% in
early hemodynamic goal-directed therapy the Control Group; 68.2±9.7% in the Car-
(GDT), aimed to maintain an elevated Do , diac Index Group; 69.7±10.5% in the ox-
2
were applied very early similarly to Rivers ygen Saturation Group) suggesting that too
et al. (4) who described that, in emergency much time was elapsed until the initiation
room, the cardio-circulatory status of sep- of the hemodynamic GDT.
tic patients, was supported according to a The benefit from a hemodynamic GDT was
close algorithm. In their study group, Riv- recently reconsidered in two trials carried
ers et al. observed a significant reduction out in major surgery setting by Pearse et al.
in mortality and morbidity vs. controls and (6) and by Lopes et al. (7).
concluded that “Early goal-directed therapy In the randomized controlled study by
provides significant benefits with respect to Pearse, high risk general surgical patients,
outcome in patients with severe sepsis and were treated according to a close post-op-
septic shock”. erative GDT (Do I ≥600 ml/min/m2), sus-
2
In a previous randomized multicentric tained with fluids and inotropes or stan-
study designed on the basis of Shoemaker’s dard treatment (Controls). otherwise from
observations, Gattinoni et al. (5), random- the previous studies, Co was measured by
ized patients in two study groups other than means of pulse power analysis (lithium
hemodynamic goal-directed therapy. A review
indicator dilution) instead of PAC. In the bidity and mortality (11). A strict moni- 57
study by Pearse et al. (6), patients in the toring of volemia and an early correction
study group, developed fewer complica- of hypovolemic states may contribute to
tions and had a lower duration of hospital prevent organ dysfunction due to low per-
stay when compared with controls even if fusion. nevertheless, it is well recognized,
no significant difference in mortality was that neither the pulmonary artery occlu-
observed. sion pressure nor the central venous pres-
In the study by Lopes et al. (7), in patients sure accurately predicts ventricular preload
undergoing high risk surgery, the hemody- or cardiac performance, either in critically
namic therapy was instituted minimizing ill patients or in normal volunteers (12). Ja-
the Pulse Pressure Variation (PPV) (Table cobs et al., confirm that dynamic measures
1), the cyclic variations induced by posi- are superior than “static” markers of pre-
tive pressure ventilation in PP (P -P ). load concluding that patients who undergo
max min
Briefly, positive pressure ventilation when vascular surgery may benefit from a close
applied to a patient at rest and with no monitoring and treatment of hypovolemia
spontaneous respiratory effort is associated with a GDT approach in which early tim-
with a cyclic increase in right atrial pres- ing is a key factor.
sure during the inflation. Since right atrial
pressure is the back-pressure to venous re- (Early) hemodynamic goal-directed therapy
turn, if upstream venous pressures do not has always been recognized as a key factor
simultaneously increase then right ven- for successful management of the critically
tricular (RV) filling will also decrease in a ill, hemodynamically unstable and high
cyclic fashion. This cyclic variation in RV risk surgical patients.
filling will induce a cyclic variation in left
ventricular (LV) filling if both RV and LV No conflict of interest acknowledged by the authors
are preload responsive.
This cyclic variation in LV filling will in- rEfErEncES
duce a cyclic variation in LV SV and arte-
1. Ganz W, Swan HCJ. Measurement of blood flow
rial PP if the patient is preload responsive.
by thermodilution. Am J Cardiol 1972; 29: 241-
Since the primary determinant of arterial 46.
PP is SV, PPV has been shown to predict 2. Shoemaker WC, Appel PL, Kram HB, et al. Pro-
preload responsiveness (Cardiac Index aug- spective trial of supranormal values of survivors
as therapeutic goals in high-risk surgical patients.
mentation of at least 15% after 500-mL
Chest 1988; 94: 1176-1186.
volume bolus) when exceeded 10-15% (8,
3. Valenza f, Aletti G, fossali T, et al. Lactate as a
9). In the study by Lopes et al. (7), mini- marker of energy failure in critically ill patients:
mizing PPV to 10% or less by means of hypothesis. Critical Care 2005; 9: 588-593.
volume loading, a lower incidence of com- 4. Rivers E, nguyen B, Havstad S, et al. Early goal-
directed therapy in the treatment of severe sepsis
plications, a lower duration of mechanical
and septic shock. n Eng J Med 2001; 345: 1368-
ventilation, and hospital stay, and a lower
1377.
(not statistically different) mortality was 5. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of
observed in the hemodynamic GDT Group goal-oriented hemodynamic therapy in critically
in respect to Controls. ill patients. n Eng J Med 1995; 333: 1025-1032.
6. Pearse R, Dawson D, fawcett J, et al. Early goal-
Recently, Jacob et al. (10) published a re-
directed therapy after major surgery reduces
view concerning the importance of fluid
complications and duration of hospital stay. A
management during vascular surgery, a
randomized, controlled trial. Critical Care 2005;
surgery burdened by a considerable mor- 9: 687-693.
S. Romagnoli, et al.
58 7. Lopes MR, oliveira MA, Pereira Vo, et al. Goal- 10. Jacob M, Chappel D, Hollmann MW. Current as-
directed fluid management based on pulse pres- pects of perioperative fluid handling in vascular
sure variation monitoring during high-risk sur- surgery. Curr opin Anaesthesiol 2009.
gery: a pilot randomized controlled trial. Critical 11. fleisher LA, Beckman JA, Brown KA, et al.
Care 2007; 11: 100. ACC/AHA 2007 Guidelines on Perioperative
8. Sorbara C, Romagnoli S, Rossi A, Romano SM. Cardiovascular Evaluation and Care for non-
Circulatory failure: bedside functional haemody- cardiac Surgery: executive summary. Circulation
namic monitoring. In: Atlee JL, Gullo A, 2nd eds. 2007;116:418-499.
Perioperative critical care cardiology. Springer- 12. osman D, Ridel C, Ray P, et al. Cardiac filling
Verlac, Italia 2007; 89-110. pressure are not appropriate to predict hemody-
9. Monnet X, Teboul JL. Volume responsiveness. namic response to fluid challenge. Crit Care Med
Curr opin Crit Care 2007; 13: 549-553. 2007; 35: 64-68.