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2015;47:90–94
The Journal of ExtraCorporeal Technology

Review Article

The History of Goal-Directed Therapy and Relevance

to Cardiopulmonary Bypass
Laurie Dijoy, BS; John Scott Dean, BS; Carla Bistrick, MS CCP; Joseph J. Sistino, PhD, CCP

Medical University of South Carolina Division of Cardiovascular Perfusion, College of Health Professions, Charleston, South Carolina

Abstract: Goal-directed therapy is a patient care strategy that has tration, neurologic injury, tissue perfusion, oxygenation, and inflam-
been implemented to improve patient outcomes. The strategy matory response. Data from these studies was compiled to document
includes aggressive patient management and monitoring during a improvements in patient outcomes. Goal-directed therapy has been
period of critical care. Goal-directed therapy has been adapted to demonstrated to improve patient outcomes when performed within
perfusion and has been designated goal-directed perfusion (GDP). the optimal time frame resulting in decreased complications,
Since this is a new concept in perfusion, the purpose of this study is reduction in hospital stay, and a decrease in morbidity. Based on
to review goal-directed therapy research in other areas of critical the successes in other critical care areas, GDP during cardiopul-
care management and compare that process to improving patient monary bypass would be expected to improve outcomes following
outcomes following cardiopulmonary bypass. Various areas of goal- cardiac surgery. Keywords: goal-directed perfusion, goal-directed
directed therapy literature were reviewed, including fluid adminis- therapy, cardiopulmonary bypass. JECT. 2015;47:90–94

Goal-directed therapy (GDT) is a patient care strategy that study is to review GDT research in other areas of critical
is designed to improve patient outcomes. This patient care care management to help understand the GDT process
strategy incorporates aggressive patient management and related to perfusion. A conceptual model for this research
monitoring during periods of critical care. The periods of crit- can be seen in Figure 1.
ical care may include peri-, intra-, or postoperative treatment
(1). Early intensive treatment is beneficial when directed
toward restoring maximal tissue perfusion through aggressive HISTORY OF GDT
management of various parameters, which may include car-
diac index, oxygen delivery, mean arterial pressure, and fluid Dr. William C. Shoemaker was one of the first physi-
therapy (2,3). cians who study the effects of GDT. In his initial publica-
GDT has been adapted to the field of perfusion, and many tion in 1988, he reported a trend of decreased mortality
of the physiologic parameters in previous GDT studies are following high-risk surgery when focusing on certain criti-
similar to those monitored by perfusionists during cardiopul- cal values. He used the term “supranormal values” to
monary bypass (4). This new application has been designated describe the elevated levels of cardiac index, oxygen deliv-
“goal-directed perfusion” (GDP) (5). The purpose of this ery, and maximal oxygen consumption seen in the survi-
vors (6). Following his observations, GDT was applied to
other areas of medicine.
In the field of emergency medicine, improved treatment
Received for publication December 2, 2014; accepted May 17, 2015. of septic shock with reduced complications was observed
Address correspondence to: Joseph J. Sistino, PhD, CCP, Division of
Cardiovascular Perfusion, College of Health Professions, Medical University when GDT was applied (7). This was accomplished by aug-
of South Carolina, 151B Rutledge Avenue, MSC 962, Charleston, SC 29425. menting the oxygen delivery index with a combination of
E-mail: sistinoj@musc.edu intravenous fluids and inotropes (8). One of the earliest and
The senior author has stated that the authors have reported no material,
financial, or other relationship with any healthcare-related business or most interesting studies using GDT was in the emergency
other entity whose products or services are discussed in this paper. room before admission to the intensive care unit (ICU) (9).

90
 HISTORY OF GDT AND RELEVANCE TO CARDIOPULMONARY BYPASS 91

Figure 1. Conceptual model for reviewing goal-directed therapy (GDT).

This application of GDP focused on adjustments of cardiac references were identified in the selected papers. A flow
preload, afterload, and contractility to balance oxygen deliv- chart for the selection of papers can be seen in Figure 2.
ery with oxygen demand to improve survival.
GDT PARAMETERS

LITERATURE SEARCH Balanced Colloid Solution

GDT using hemodynamic algorithms for the administra-
PubMed was used to search for publications on the sub- tion of a balanced crystalloid solution vs. a 6% hydroxyethyl
ject of GDT and goal-directed perfusion (GDP). The initial starch colloid solution was reported (10,11). This double-
search term was “goal-directed perfusion,” which yielded blinded study was randomized in 50 patients undergoing
only three articles. The search was then expanded to “goal- major pelvic surgery. Each patient received fluids to opti-
directed therapy” combined with “cardiac surgery,” “intra- mize stroke volume. Renal function was normal in both
operative care,” and “high risk surgery.” A total of 1,221 groups when fluid administration was targeted to optimize
articles were found and 13 were selected for this review on cardiac preload. There was no difference between the patient
the basis of the inclusion parameters. The inclusion param- groups in either ICU or hospital length of stay. However,
eters were stroke volume, cardiac index, oxygen delivery, patients that received a balanced colloid solution had an
oxygen consumption, and fluid therapy. Three additional increased stroke volume with less fluid administration and
required less units of fresh frozen plasma compared with
those that received the crystalloid solution.
Oxygen Extraction Ratio
GDT using the oxygen extraction ratio (O2ER) as a mea-
sure of tissue hypoxia leading to organ dysfunction was
reported. All patients received treatment to maintain a mean
arterial pressure >80 mmHg and urinary output >.5 mL/kg/h.
The study group was treated to maintain an O2ER < 27%
(11). In this randomized study, the primary outcomes were
the rate of postoperative organ failure and the length of
hospital stay. The results revealed that overall mortality was
the same in both groups. However, there were significantly
less patients with single organ failure or multiple organ sys-
tem failure in the study group. This resulted in a decrease in
the length of hospital stay for the study group.
Hemodynamic Algorithm
Figure 2. Flow chart for selection of research papers related to goal- This study looked at a combination of functional and
directed therapy (GDT). volumetric parameters to improve outcomes in cardiac

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92 L. DIJOY ET AL.

surgery patients (12). A prospective trial was conducted in associated with three independent factors; age, randomiza-
patients who underwent either a coronary artery bypass tion to GDT, and the avoidance of significant postoperative
grafting (CABG) procedure, an aortic valve replacement cardiac complications. Although many papers do not dem-
(AVR) procedure, or combined AVR/CABG procedures. onstrate an improvement in short-term survival, GDT is
Fifty patients were randomized into two groups. In the con- associated with a reduction in complications, which signifi-
trol group, the mean arterial pressure (MAP) was main- cantly improves long-term survival.
tained greater than 65 mmHg and central venous pressure
(CVP) greater than 8 mmHg. The study group had hemo-
GOAL-DIRECTED PERFUSION
dynamic therapy guided by stroke volume, end-diastolic
volume index, mean arterial pressure, and cardiac index.
GDT has been practiced for nearly 30 years, but it still
Therapy started after induction of anesthesia and continued
remains to be determined if there is a significant role for
until ICU discharge. The study group had significantly lower
GDT in perfusion. The role of the perfusionist in provid-
intraoperative norepinephrine requirements, decreased post-
ing cardiopulmonary support has been historically outlined
operative complications, and a reduction in ICU length
in broad terms (17), but is continually being redefined as
of stay.
evidence-based patient care is updated (5).
Review of GDT in Cardiac Surgery GDP aims to use intensive monitoring during cardiopul-
A review paper for the use of GDT in cardiac surgery monary bypass (CPB) to reduce mortality and postopera-
included five studies. Patient mortality and morbidity fol- tive complications. Perfusionists have the opportunity to
lowing cardiac surgery were studied related to the pH of administer therapy to patients intraoperatively, which is
gut mucosa, stroke volume index, cardiac index, systemic one of the most critical times for GDT. There have been
vascular resistance, and oxygen delivery (1). This review many advances in perfusion to improve the mortality and
article concluded that even if GDT does not reduce post- the morbidity of the patients undergoing cardiac surgery,
operative mortality, it does reduce morbidity and there- and these should be included as part of GDP (5,15,18).
fore warrants inclusion in high-risk patients. New guidelines and standards for perfusionists were
published in 2013 by the American Society of ExtraCor-
Meta-Analysis GDT poreal Technology (4). These guidelines include standards
A meta-analysis was done to determine the effects of for the perfusionist to minimize prime volume, evaluate
perioperative GDT on mortality and morbidity in cardiac and optimize gas exchange, and calculate oxygen delivery
and vascular surgery (13). Their search consisted of key and consumption for each patient. Though these guide-
words including “cardiac index, oxygen delivery, oxygen lines are in strong agreement and promote the philosophy
consumption, stroke volume, fluid therapy, and fluid of GDP, they do not give suggested values or parameters
loading.” Eleven articles were included in the analysis for perfusionists to take into consideration for patient care
(n = 1,179 patients). Patients were randomized to either while on CPB.
perioperative GDT or routine hemodynamic management.
The results demonstrated that perioperative GDT did not
reduce mortality following cardiac or vascular surgery and OPTIMAL PERFUSION
there were no significant reduction in complications in the
vascular surgery patients. However, GDT significantly reduced Clinical evidence can be used to guide CPB parameters
the number of complications in cardiac surgery patients to achieve “optimal” perfusion (19). Optimal perfusion
with an odds ratio of .35 (13). requires intensive and focused monitoring to maintain the
A second meta-analysis was conducted to determine desired parameters within a very narrow therapeutic range
if GDT could reduce surgical mortality, morbidity, and length for each individual patient. This goal-directed patient
of hospital stay in cardiac surgical patients (14). Although management should be associated with optimal oxygen
there was no significant reduction in mortality, GDT signifi- delivery (DO2) and tissue perfusion with reduced inflam-
cantly reduced postoperative complications and the length matory response, preservation of the coagulation cascade,
of hospital stay. maintenance of colloid oncotic pressure, and fluid balance.
This results in “the best long-term patient outcome in
Long-Term Outcome terms of survival and function of all major organ systems”
One experimental study in cardiac surgery patients in resulting in low morbidity and reduced postoperative
whom GDT was used demonstrated a significant reduction recovery periods (19).
in mortality (15). In a long-term follow-up (15 years) of
these patients, survival was significantly greater in the study Optimal Mean Arterial Pressure
group (16). Of the GDT patients, 20.7% were still alive vs. A randomized study of patients assigned to either high
7.5% of the control group (16). Long-term survival was (>70 mmHg) or low (50–60 mmHg) mean arterial pressures

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 HISTORY OF GDT AND RELEVANCE TO CARDIOPULMONARY BYPASS 93

on CPB was conducted for patients undergoing CABG. DISCUSSION

The study concluded that there were improved short- and
long-term outcomes in the higher pressure group. Mortality Although some of the information provided in the review
rates in this group were approximately 50% less than the of optimal perfusion parameters may seem contradictory,
lower pressure group and the incident of stroke was three we must also consider differences in patients. GDP aims to
times lower. Cardiac and neurological complications were deliver specialized care to each patient on the basis of their
two and one-half lower as well (20). unique history and distinct needs. Individualized patient
care is critical to reducing postoperative complications
Optimal Arterial Blood Flow and mortality. GDP can target individual patient require-
Arterial blood flow rates to deliver optimal tissue per- ments by making focused, micro-level adjustments based
fusion were evaluated. The most commonly used flow on the needs of a specific patient. It takes into account
rates during CPB ranged from 2.2 to 2.5 L/min/m2 (21). real-time values of the patient and can use computer-based
High and low flow rates were examined in various clinical notification when critical values are trending outside their
experiments with inconclusive results on the optimal flow accepted ranges. Increased use of electronic medical records
for all patients. It was suggested that lower pump flows may will allow perfusionists to improve patient management in
compromise visceral organs because of the lower blood flow a more proactive manner, rather than identifying outlying
to these areas. parameters when reviewing the perfusion record following
the procedure. GDT applied to perfusion provides a new
opportunity to improve patient care during the critical period
Optimal Hematocrit of cardiac surgery.
The optimal hematocrit during CPB appears to be
above 23–24% in both adult and pediatric patients (21,22)
The studies reviewed showed that hematocrits below this CONCLUSION
level trended toward increased morbidity and mortality,
with significant association of postoperative complications GDT has provided a strong basis for the development of
including in-hospital mortality ( p < .001), intra- or post- GDP. Many studies have attempted to determine optimal
operative placement of an intra-aortic balloon pump ( p < patient management parameters; however, newer evidence
.001) and return to CPB after initial separation ( p < .001). has shown that intensive monitoring of key parameters
It was found that in the adult patients whose hematocrit was during critical periods of patient treatment have a pro-
less than 19%, there was an approximate 100% increase found impact on improving long-term survival.
in morbidity (21). However, increasing the hematocrit with
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