Journal Reading

Perioperative Fluid and Volume Management: Physiological

Basis, Tools and Strategies

Guide : dr. Agustinus Juhardi MSc, Sp.An

By :
Debbie Cinthia Dewi
11-2014-194

Registrar of Anesthesia Clinical Studies

Mardi Rahayu Kudus Hospital
Faculty of Medicine Universitas Kristen Krida Wacana
Kudus
2015

Perioperative Fluid and Volume Management: Physiological Basis,

Tools and Strategies
Mike S Strunden1,2*, Kai Heckel1,2, Alwin E Goetz1,2, Daniel A Reuter1,2
Abstract
Fluid and volume therapy is an important cornerstone of treating critically ill patients
in the intensive care unit and in the operating room. New findings concerning the
vascular barrier, its physiological functions, and its role regarding vascular leakage
have lead to a new view of fluid and volume administration. Avoiding hypervolemia,
as well as hypovolemia, plays a pivotal role when treating patients both
perioperatively and in the intensive care unit. The various studies comparing
restrictive vs liberal fluid and volume management are not directly comparable, do
not differ (in most instances) between colloid and crystalloid administration, and
mostly do not refer to the vascular barriers physiologic basis. In addition, very few
studies have analyzed the use of advanced hemodynamic monitoring for volume
management.
This article summarizes the current literature on the relevant physiology of the
endothelial surface layer, discusses fluid shifting, reviews available research on fluid
management strategies and the commonly used fluids, and identifies suitable variables
for hemodynamic monitoring and their goal directed use.
Introduction
There is increasing evidence that fluid management influences patients outcome as
well in critical illness, as during and after major surgery. Hence, the numerous
different aspects contributing to fluid management have been in the focus of both
basic and clinical research during the past years. Basically three questions are
intrinsically tied to fluid administration perioperatively and in critically ill patients: 1)
What happens to intravascular fluid in health and disease? 2) How do different
intravenous fluids behave after application? 3) What are the goals for volume
administration and how can they be assessed and reached? Current basic research
brought fascinating insights of the function of the endothelial vascular barrier and, in
particular, regarding functional changes that lead to vascular leakage. Experimental
and clinical trials investigating the effects of both crystalloid and colloid solutions and
their natural and artificial representatives have shown quite conflicting results. The
same accounts for the mainly clinical studies that primarily focussed on clinical goals
to guide perioperative volume therapy. However, all of those three aspects cannot be
separated from each other when defining rational strategies for fluid management.
Thus, this review article summarizes the knowledge of the function and dysfunction

of the endothelial vascular barrier, on the effect of different intravenous fluids and on
the opportunities of hemodynamic monitoring to enable drawing conclusions for
rational concepts of perioperative fluid and volume management.
The Underlying Aspects
The physiologic basis: why does fluid stay within the vasculature?
Two thirds of human body fluid is located in the intracellular compartment. The
remaining extracellular space is divided into blood plasma and interstitial space. Both
compartments communicate across the vascular barrier to enable exchange of
electrolytes and nutriments as the basis for cell metabolism. The positive intravascular
pressure continuously forces blood toward the interstitial space. Under physiologic
conditions, large molecules, such as proteins and colloids, cannot cross the barrier in
relevant amounts, which is a necessity for the regular function of circulation.
Otherwise, the intravascular hydrostatic pressure would lead to uncontrollable loss of
fluid toward the interstitial space and disseminated tissue edema [1]. In 1896, Ernest
Starling suggested an interstitial colloid osmotic pressure far below the intravascular
pressure. The concentration gradient across the vascular barrier generates a flow,
which is directed into the vasculature and opposes the hydrostatic pressure resulting in
an only low filtration per unit of time. According to the Starling principle, only the
endothelial cell line is responsible for the vascular barrier function [1]. In a rat
microvessel model, it has been shown that the interstitial colloid osmotic pressure was
nearly 70% to intravascular osmotic pressure without causing interstitial edema,
which is in contrast to the Starlings concept, suggesting an only minor role for the
interstitial protein concentration [2]. The endothelial glycocalyx plays a pivotal role in
this context. Every healthy vascular endothelium is coated by transmembrane
syndecans and membrane-bound glypicans containing heparan sulfate and chondroitin
sulfate side chains, which together constitute the endothelial glycocalyx [3,4]. Bound
plasma proteins, solubilized glycosaminoglycans, and hyaluronan are loading the
glycocalyx to the endothelial surface layer (ESL), which is subject of a periodic
constitution and degradation. Under physiologic conditions, the ESL has a thickness
of approximately 1 m and binds approximately 800 ml of blood plasma, so plasma
volume can be divided into a circulating and noncirculating part [4,5]. Accordingly,
the glycocalyx seems to act as a molecular filter, retaining proteins and increasing the
oncotic pressure within the endothelial surface layer. A small space between the

anatomical vessel wall and the ESL remains nearly protein free [2]. Thus, fluid loss
across the vascular barrier is limited by an oncotic pressure gradient within the ESL
[6]! Starlings classic principle was therefore modified to the double-barrierconcept in which not only the endothelial cell line but primarily the endothelial
surface layer constitutes the vascular barrier [6].
Vascular Barrier Dysfunction: Reasons and Consequences
The ESL constitutes the first contact surface between blood and tissue and is involved
in many processes beside vascular barrier function, such as inflammation and the
coagulation system. A number of studies identified various agents and pathologic
states impairing the glycocalyx scaffolding and ESL thickness. In a genuine pig heart
model, Chappell et al. demonstrated a 30-fold increased shedding of heparan sulphate
after postischemic reperfusion [7]. These data were approved by a clinical
investigation, which showed increased plasma levels of syndecan-1 and heparan
sulphate in patients with global or regional ischemia who underwent major vascular
surgery [8]. Beside ischemia/reperfusion injury, several circulating mediators are
known to initiate glycocalyx degradation. Tumor necrosis factor (a), cytokines,
proteases, and heparanase from activated mast cells are well-described actors in
systemic inflammatory response syndrome leading to reduction of the ESL thickness,
which triggers increased leucocyte adhesion and trans- endothelial permeability
[7,9,10]. Interestingly, hypervolemia also may cause glycocalyx impairment mediated
by liberation of atrial natriuretic peptide [11]. Hypervolemia resulting from
inadequately high fluid administration therefore may cause iatrogenic glycocalyx
damage. As shown in basic research, the dramatic consequence of a rudimentary
glycocalyx, which loses much of its ability to act as a second barrier, is strongly
increased transendothelial permeability and following formation of interstitial edema
[7,11]. The relevance of these experimental data were impressively underlined by
Nelson et al., who found increased plasma levels of glycosaminoglycans and
syndecan-1 in septic patients, wheres median glycosaminoglycan levels were higher
in patients who did not survive [12].
Fluid Balance: where does fluid get lost?
Urine production and insensible perspiration are physiologically replaced by free
water absorbed from the gastrointestinal system and primarily affect the extravascular

space, if they are not pathologically increased. Because the physiologic replacement is
limited in fasted patients, it has to be compensated artificially by infusing crystal
loids. The composition of the used infusion should be similar to the physiologic
conditions to avoid acid-base disorders, which mostly accounts for balanced
crystalloid infusions. During surgery, trauma or septic shock additional fluid loss
(blood loss, vascular leakage) affects mainly the intravascular compartment [13,14].
Consequently, the first type of fluid loss is attenuated by redistribution between
intracellular, interstitial, and intravascular space slowly and causes dehydration,
whereas the second type of loss leads to acute hypovolemia. Preoperative
hypovolemia after an overnight fasting period, as described in anesthesia text books
[15,16], cannot be explained by the considerations above and does not occur regularly
in all patients [17]. Fluid reloading is unjustified, at least in cardiovascular healthy
patients before low-invasive surgery [17]. Mediated by increased liberation of atrial
natriuretic peptide, undifferentiated fluid loading can cause glycocalyx degradation,
increase vascular permeability, promote tissue edema formation and therefore may
constitute a starting point of the vicious circle of vascular leakage and organ failure
[11,18]. Fluid loss from insensible perspiration also is obviously overestimated in
many patients, although loss of only 1 ml/kg per hour occurs even when the
abdominal cave is opened [19]. In theory, it should be adequate to substitute only the
losses described earlier to maintain a normal blood volume in the critically ill patient.
Based on the assumption that a generous fluid administration could prevent
hypotension and postoperative renal failure, frequently much greater amounts are
infused perioperatively [20], although there is no evidence that the incidence of renal
failure is decreased by a liberal infusion regimen during surgery [21]. Furthermore,
prophylactic crystalloid infusion does not influence the occurrence of hypotension
caused by vessel dilatation [22]. Nevertheless, patients require much more
intravenous fluids than suggested by physiologic considerations. Shown by blood
volume measurements, major surgery causes a deficit of 3-6 liters in the perioperative
fluid balance [23,24]. The peak even persists up to 72 hours after trauma or surgery
[25]. The common explanation for this phenomenon is a fluid shift into the so-called
third space. This third space can be divided into an anatomic and a nonanatomic
part. Physiologic fluid shifting from the vessel toward the interstitial space across an
intact vascular barrier contains only small amounts of proteins. It does not cause
interstitial edema as long as it can be quantitatively managed by the lymphatic system.

Losses into the anatomic third space are based on this mechanism but in a
pathologic quantity [13,14], which transgresses the capacity of the lymphatic system.
The nonanatomic third space, in contrast, is believed to be a compartment separated
from the interstitial space [13,14]. Losses toward this compartment are assumed to be
trapped and lost for extracellular exchange. Cited examples for nonanatomic third
space losses are fluid accumulation in traumatized tissue, bowel, or peritoneal cavity
[15,16], but despite intensive research, such a space has never been identified! Fluid is
shifted from the intravascular to the interstitial space! This fluid shift can be classified
into two types [13]:
Type 1, occurring always and even if the vascular barrier is intact, represents
the physiologic, almost protein free shift out of the vasculature. Occasionally it
emerges at pathologic amounts.
Type 2, the pathologic shift is caused by dysfunction of the vascular barrier. In
contrast to type 1, fluid crossing the barrier contains proteins close to plasma
concentration [13]. This shift has basically three reasons. First, surgical manipulation
increases capillary protein permeability excessively [26]. Interstitial fluid raised
approximately 10% during realization of an enteral anastomosis in a rabbit without
any fluids being infused [27]. Concomitant administration of 5 ml/kg of crystalloid
infusion even doubled this edema. Second, reperfusion injury and inflammatory
mediators compromise the vascular barrier [7-10]. Third, iatrogenic hypervolemia can
lead to glycocalyx degradation and cause an extensive shift of fluid and proteins
toward the tissue [23,24]. The pathologic shift affects all intravenous fluids. Opposed
to the common believe that, in contrast to crystalloids, colloids would stay within the
vasculature, Rehm et al. described a volume-effect >90% only when a tetrastarch
solution was infused titrated to the actual intravascular volume loss. Administered as a
bolus in a normovolemic patient, two thirds of the infused volume left the vasculature
immediately [23,24]. Volume resuscitation with colloids obviously requires careful
titration to current losses to avoid a remarkable protein shift toward the interstitial
space [14]. Based on the double-barrier concept, hypoproteinemia even intensifies a
vascular barrier dysfunction and promotes tissue edema formation. Perioperative fluid
shifting is reflected in clinical data published two decades ago. Lowell et al. showed a
weight gain of more than 10% in >40% of patients admitted to the intensive care unit
after major surgery. This increase of body weight, representing interstitial edema,
correlated strongly with mortality [28].

Dehydration or Hypovolemia?
Dehydration, affecting primarily the extravascular compartment, and acute
hypovolemia are two different diagnoses and deserve different therapeutic
considerations. Urine production and insensible perspiration cause a loss of colloid
free fluid, which, due to redistribution between intravascular and extravascular space,
does normally not impair the intravascular compartment directly. Thus, the resulting
dehydration has to be treated by refilling the extravascular space and replacing further
losses by crystalloid administration [13]. In contrast, acute hypovolemia at first affects
the intravascular compartment. Because crystalloids distribute freely between
interstitial and intravascular space, they are not suitable for volume resuscitation in
acute hypovolemia. Lost colloids and proteins cause a decreased intravascular oncotic
pressure, which would be aggravated by administration of colloid-free intravenous
fluid and would enforce the formation of interstitial edema. Thus, fluids that mainly
remain within the vasculature and maintain oncotic pressure are needed to treat acute
loss of plasma volume effectively: colloids.
Intravenous fluids: crystalloids and colloids
Crystalloids
Crystalloids freely distribute across the vascular barrier. Only one fifth of the
intravenously infused amount remains intravascularly [15,16]. Proclaimed by textbooks, a fourfold amount of crystalloid infusion is needed to reach comparable
volume effects as achieved with colloid administration. Whereas this is true if the
vascular barrier is intact, in patients suffering from capillary leakage ratios from only
1.6:1 to 1:1 (crystalloid to colloid infusion) were observed to reach equivalent effects
[29,30]. Nevertheless, colloid treatment resulted in a greater linear increase in cardiac
preload and output in septic and nonseptic hypovolemic patients compared with
crystalloid administration [31], and its volume expansion lasted longer during acute
hemorrhage experimentally [32]. Although currently discussed, regarding the doublebarrier concept one could assume that colloids distribute nearly as freely as
crystalloids across a seriously impaired vascular barrier. However, volume
resuscitation with crystalloid infusions was associated with serious complications,
such as respiratory distress syndrome, cerebral edema, and abdominal compartment
syndrome in patients with major trauma [33-35] and promotes the development of
hyperchloremic acidosis [36]. Even if there is ongoing discussion about the benefits

and risks of balanced crystalloid solutions, their use is beneficial to avoid acid-base
disorders [25].
Colloids
The only natural colloid used in clinical matters is albumin. The artificial colloids
hydroxyethyl starch (HES) and gelatin are used prevalently in European countries,
whereas albumin is applied less commonly [37].
Albumin
Under physiologic conditions, albumin is the molecule mainly accountable for
intravascular osmotic pressure and should be an ideal colloid to restore protein loss
from the vasculature. However, as a natural colloid, albumin may cause severe
allergic reaction and immunologic complications. Current date concerning albumin
use to treat hypovolemia mainly originate from critically ill patients. A Cochrane
review of 30 randomized, con- trolled trials, including 1,419 patients with
hypovolemia, showed no evidence for a reduced mortality comparing albumin to
crystalloid volume resuscitation. Usage of albumin may contrariwise even increase
mortality [38]. More recently, the SAFE Study, including 6,997 patients and
comparing albumin to normal saline fluid resuscitation, found neither beneficial
effects nor an increased mortality in the albumin group. Additionally, no differences
in days of mechanical ventilation or need for renal-replacement therapy were
observed [39]. In con- trast to isooncotic albumin, which does not influence the
outcome of critically ill patients, treatment with hyperoncotic albumin increased
mortality [40]. Therefore, administration of isooncotic albumin may be justifiable in
particular cases but not as a routine strategy for volume resuscitation.
Gelatins
Gelatins are polydispersed polypeptides from degraded bovine collagen. The average
molecular weight of gelatin solutions is 30,000 to 35,000 Da and their volumeexpanding power is comparable. Several studies have examined the pharmacological
safety of gelatins. In brief, all preparations are said to be safe in regard to coagulation
and organ integrity [15,16] except kidney function. Mahmood et al. demonstrated
higher levels of serum urea and creatinine as a more distinct tubular damage in
patients treated with 4% gelatin solution compared with hydroxyethyl starch (HES)
solutions while undergoing aortic aneurysm surgery [41]. There- fore, use of gelatins
is limited in renal-impaired patients.

Hydroxyethyl starch
Hydroxyethyl starch, an artificial polymer, is derived from amylopectin, which is a
highly branched chain of glucose molecules obtained from waxy maize or potatoes.
Conservation

from

degradation

and

water

solubility

are

achieved

by

hydroxyethylation of the glucose units HES solutions are available in several

preparations and vary in concentration, molecular weight, molar substitution, C2/C2
ratio, solvent, and pharmacologic profile. Although small HES molecules (< 50-60
kD) are eliminated rapidly by glomerular filtration, larger molecules are hydrolyzed to
smaller fractions and are partially taken up in the reticuloendothelial system. Although
this storage seems not to impair the mononuclear pha- gocytic system, it is remarkable
that low molecular weight HES accumulates less compared with high molecular
weight HES [42]. Negative effects of high molecular HES on the coagulation system
are well described. Preparations >200 kD lead to a reduction of von Willebrand factor
and factor VIII, causing a decreased platelet adhesion. Low molecular weight
preparations, such as HES 130/0.4, have only minimal effects on coagulation. HES in
balanced solution increases the expression of activated platelet GP IIb/IIIa, indicating
an improved hemostasis [43,44]. Focusing on kidney function, an 80% rate of
osmotic nephrosislike lesions and impaired renal function were reported in kidney
transplant recipients after administration of HES 200/0.62 to brain-dead organ donors
[45,46]. In septic patients, usage of 10% HES 200/0.5 correlated with a higher
incidence of renal failure compared with crystalloids [47]. Admittedly, HES was
administered without regard to exclusion criteria and dose limitations in this study.
The most likely pathomechanism of renal impairment by colloids is the induction of
urine hyperviscosity by infusing hyperoncotic agents in dehydrated patients.
Glomerular filtration of hyperoncotic molecules causes a hyperviscous urine and
results in stasis of the tubular flow [48]. Elevated plasma oncotic pressure, regardless
of which genesis, is known to cause acute renal failure since more than 20 years [49].
Based on this pathogenesis, all hyperoncotic colloids may induce renal damage,
whereas isooncotic tetra starch solutions, such as 6% HES 130/0.4, seem not to impair
renal function [41,46]. After administration of extremely high application rates (up to
66 liters in 21 days) in patients with severe head injury, no impairment of renal
function was observed [50]. In contrast to results of the VISEP study [47], the SOAP
study, which included more than 3,000 critically ill septic patients treated with
pentastarch and tetrastarch solutions, also showed no higher risk for renal failure [51].

Hydroxyethyl starch was administered in much lower amounts (13 vs. 70 ml/kg) and
for a shorter period in the SOAP study. There is evidence that HES also modulates
inflammation. Synthetic colloids inhibit neutrophil adhesion to the endothelium and
neutrophil infiltration of the lung [52,53].
Furthermore, HES attenuated inflammatory response in septic rats as well as in rats
volume resuscitated with HES 130/0.4 during severe hemorrhagic shock by
decreasing tumor necrosis factor-alpha, interleukins, and oxidative stress [53,54].
Although advantageous aspects of volume replacement with so-called modern
isooncotic tetrastarch solutions, in particular in reaching early hemodynamic stability
are comprehensible [31,32], data on focussed, adequately powered, prospective
clinical trials proving their outcome-relevance are needed.
Goals and stategies for volume replacement
Because the primary goal of the cardiovascular system is to supply adequate amounts
of oxygen to the body and to match its metabolic demands, the target of volume
management is to maintain adequate tissue perfusion to ensure tissue oxygenation.
Hypovolemia, as well as hypervolemia, decreases tissue perfusion and may result in
organ failure [55-59]. Even supplemental oxygen does not improve oxygenation in
hypoperfused tissue [60]. Because hypovolemia is a frequent cause for hemodynamic
deterioration in critically ill patients, securing an adequate intravascular volume is a
cornerstone of hemodynamic management. But how can we assess adequate
intravascular volume? Because the relation between hemodynamic variables is
complex in health already, it is even more complex in disease and their interpretation
requires a solid understanding of cardiovascular regulation mechanism.
In hemodynamic unstable patients, basically four functional questions need to be
answered. Because the primary goal of resuscitation is to secure tissue oxygenation,
the first question is already the most decisive, but also the most difficult one: Is tissue
oxygenation adequate? Because representative tissue oxygenation is not measurable
directly, primarily three variables are used as surrogates: mixed venous oxygen
saturation; central venous oxygenation; and serum lactate. Use, interpretation, and
significance of these parameters concerning assessment of tissue oxygenation are
discussed elsewhere. In brief, none of them is able to detect tissue oxygen debt
definitely, because every single one is influenced by various morbidities and drug
interactions [61-64]. The second question is: How can cardiac output (CO), as the

main determinate of oxygen delivery, be improved? Or, better representing clinical

matters: Is the patient volume responsive? The third question regards the vasomotor
tone: Is it increased, decreased, or normal in the hypotensive patient? Fourth, heart
work: Is the heart able to sustain an adequate CO when arterial pressure is restored
without going into failure [65]?
Usually physicians address these questions by measuring mean arterial pressure
(MAP), central venous pressure (CVP), and by observing diuresis [66]. All of these
parameters are easy to measure, but actually do not allow to assess hemodynamic
instability sufficiently or to differentiate its cause adequately. If disease leads to a
decrease of CO, the physiologic reaction of the body, mediated by baroreceptors, is to
restore the like wise decreased arterial pressure to maintain cerebral perfusion
pressure [67]. This is frequently accompanied by tachycardia, caused by modulation
of the sympathetic tone. Hence, hypotension reflects the failure of this compensating
mechanism, whereas normotension does not automatically ensure hemodynamic
stability [68]. In addition, tachycardia and hypotension can be absent during
hypovolaemic shock until intravascular volume loss reaches 20% or more [69,70].
CVP shows a poor correlation to blood volume [71], is inadequate to detect
hypovolemia reliably, and most notably cannot sense a decreased cardiac output and
tissue oxygen debt in an early state. Furthermore, changes in CVP after volume
administration do not allow any conclusions to changes in stroke volume (SV) or
cardiac output (CO) [72]. Measuring CVP is therefore inadequate to assess the
patients hemodynamics and to manage volume resuscitation. Because CO is the
primary determinate by which oxygen donation to the tissue is varied to match
metabolic requirements, the effectiveness of a resuscitation therapy can be evaluated
best by continuous monitoring of cardiac output. Several different methods, ranging
from the classical indicator dilution techniques to less invasive approaches, such as
arterial pulse contour analysis and Doppler techniques, are clinically available. A
detailed description and discussion of their individual advantages and disadvantages is
beyond the scope of this article and can be found in recent reviews [73,74]. Suitable
monitoring techniques for defining treatment strategies are able to assess cardiac
output as well as cardiac preload and, first of all, to predict volume responsiveness of
the patient, which mostly applies to volumetric and functional parameters utilizing the
heart-lung interaction under mechanical ventilation [75-78]. In the past, various
studies were published that favored individual concepts of perioperative volume

management strategies. Most of them originated from perioperative care and focussed
primarily on the treatment in the operating room. Of course, those strategies impact
postoperative ICU treatment as well. Restrictive strategies were compared with
permissive or liberal ones. However, commonly accepted definitions of
restrictive or liberal fluid strategies do not exist, making those studies nearly
incomparable. Investigators normally labelled their traditional standard fluid regimen
the standard group and compared it with their own restrictive fluid administration
model. Liberal in one study was already restrictive in the other trial and fluid
administration followed rigid schemas or different goals. Additionally, endpoints of
the given studies varied from postoperative vomiting, pain, or tissue oxygenation to
bowel recovery time, which de facto rules out a comparison [79-82]. One of the most
cited studies in this regard is the work of Brandstrup et al., who demonstrated that
perioperative fluid restriction (2740 vs. 5388 ml) reduced the incidence of
anastomotic leakage, pulmonary edema, pneumonia, and wound infection in 141
patients undergoing major colorectal surgery without increasing renal failure rate.
Interestingly, a closer look at the infusion protocol reveals a comparison between
crystalloid versus colloid fluid administration. The restrictive group received mainly
colloids, whereas the liberal group was treated exclusively with crystalloids [79]. All
of those studies have in common that no hemodynamic goals were set, which is in
contrast to the goal-directed-therapy (GDT) approach known most prominently
from the study by Rivers et al., in which the authors used central venous pressure,
mean arterial pressure, serum lactate, and mixed venous oxygen saturation as goals to
optimize the early treatment in septic patients [83]. Further peri and postoperative
studies in surgical patients underline the importance of functional hemodynamic
goals to improve patients outcome. In a meta-analysis encasing four prospective
randomized trials, cardiac output guided fluid management reduced hospital stay and
lessened complication rate [84]. Additionally, interleukin-6 response was attenuated in
a colorectal surgery study using a Doppler-optimized goal-directed fluid management
[85]. Gopfert et al. reported a reduced time of mechanical ventilation and intensive
care unit stay in cardiac surgery patients using the global end-diastolic volume index
and cardiac output to manage volume administration [86]. The extravascular lung
water index may be a useful tool for GDT, too, and is subject of current discussion
[87]. Furthermore, goal-directed fluid therapy reduces inflammation, morbidity, and

mortality not only in severe sepsis and septic shock, but also in patients who undergo
major surgery [88-90].
Conclusions
Consolidated findings regarding the endothelial surface layer led to a new
comprehension of the vascular barrier. Starlings principle was adjusted to the
double-barrier concept and the mechanisms of ESL alteration in critically ill
patients seem to play a major role in tissue edema formation. Because glycocalyx
diminution leads to an increased capillary permeability, fluid loss toward the
interstitial space, commonly considered to be a loss toward the third space, is one
major consequence of ESL degradation. Studies concerning fluid and volume therapy
prove an adverse effect of tissue edema formation on organ function and mortality.
Therefore, knowledge of the consequences of infusing different types of crystalloids
and colloids during physiologic and pathologic states is necessary. Furthermore, fluid
and volume administration are two different therapies for two different diagnoses.
Dehydration resulting from urine loss, preoperative fasting, and insensible
perspiration requires fluid administration primarily based on crystalloid infusions.
Intravascular volume deficit, i.e., acute hypovolemia, resulting in a decreased cardiac
output requires volume replacement, where colloid administration appears
meaningful, although current clinical data are not finally consistent. The right amount
of administered volume should be titrated goal directed using a strategy based on
macro-hemodynamic parameters of flow and volume.

Bacaan Jurnal
Manajemen Cairan dan Volume Perioperatif : Berdasarkan
Fisiologis, Pengaturan dan Strategi

Pembimbing : dr. Agustinus Juhardi MSc, Sp.An

Oleh :
Debbie Cinthia Dewi
11-2014-194

Kepaniteraan Klinik Ilmu Anestesi

Rumah Sakit Mardi Rahayu Kudus
Fakultas Kedokteran Universitas Kristen Krida Wacana
Kudus
2015

Manajemen Cairan dan Volume Perioperatif : Berdasarkan

Fisiologis, Pengaturan dan Strategi
Mike S Strunden1,2*, Kai Heckel1,2, Alwin E Goetz1,2, Daniel A Reuter1,2
Abstrak
Terapi cairan dan volume merupakan landasan penting dalam merawat pasien yang
sakit kritis di unit perawatan intensif dan di ruang operasi. Temuan terbaru mengenai
lapisan dinding pembuluh darah atau endothelium, serta fungsi fisiologis, dan peran
mengenai kebocoran plasma telah memberikan pandangan baru tentang pemberian
cairan dan volume. Dalam menghindari keadaan hypervolemia, serta hipovolemia,
memainkan peranan yang sangat penting ketika merawat pasien selama operasi dan
pasien di unit perawatan intensif. Berbagai studi membandingkan pemberian cairan
dan volume secara restriktif atau dibatasi dengan pemberian yang banyak secara
langsung tidak dapat disamakan, tidak begitu berbeda (dalam kebanyakan kasus)
antara pemberian koloid dan pemberian kristaloid pada sebagian besar kasus tidak
mengacu pada dasar fisiologis, dan pembuluh darah. Selain itu, sangat sedikit
penelitian yang telah menganalisis penggunaan serta pemantauan hemodinamik
canggih untuk manajemen cairan dan volume.
Artikel ini merangkum literatur tentang fungsi fisiologi secara nyata berdasarkan
lapisan permukaan endotel, membahas distribusi cairan, ulasan penelitian tentang
strategi manajemen cairan dan cairan yang umum digunakan, dan mengidentifikasi
variabel yang sesuai untuk pemantauan hemodinamik dan tujuan penggunaan yang
diarahkan berdasarkan kebutuhan.
Pendahuluan
Banyak sumber yang mengatakan bahwa manajemen cairan mempengaruhi perbaikan
keadaan pasien pada keadaan kritis saat selama dan setelah operasi besar. Oleh karena
perbedaan jumlah aspek yang berkontribusi tentang manajemen cairan akhirnya
penelitian terfokus kepada hal dasar dan klinis yang telah diteliti selama beberapa
tahun terakhir. Pada dasarnya ada tiga hal secara intrinsik terkait dengan pemberian
cairan pada pasien perioperatif dan pasien sakit kritis: 1) Apa yang terjadi pada cairan
intravaskular pada keadaan sehat dan sakit? 2) Bagaimana perbedaan efek pada saat
pemeberian cairan infus? 3) Apa tujuan pemberian cairan, apa saja yang dinilai dan
apa telah mencapai kadarnya? Penelitian berdasarkan fungsi dinding pembuluh
endotel dan khususnya mengenai perubahan fungsional yang menyebabkan kebocoran
pembuluh darah memberikan pengetahuan yang menarik. Hasil dari uji penelitian dan
hasil klinis dasar, memberikan perbedaan efek dari kedua larutan kristaloid dan koloid
yang alami dan buatan menunjukkan hasil yang cukup bertentangan. Hal yang sama

ditujukan berdasarkan hasil studi terutama klinis yang difokuskan pada tujuan untuk
memandu terapi cairan dan volume pasien perioperatif. Namun, semua dari ketiga
aspek tersebut tidak dapat dipisahkan satu sama lain ketika mendefinisikan strategi
yang rasional untuk manajemen cairan. Dengan demikian, review artikel ini
merangkum pengetahuan tentang fungsi dan disfungsi dinding lapisan pembuluh
darah, pada efek dari cairan infus yang berbeda dan pada kesempatan pemantauan
hemodinamik untuk memungkinkanya menarik kesimpulan tentang konsep yang
benar dalam pemberian cairan perioperatif dan manajemen volume.
Aspek yang mendasari
Dasar fisiologis: mengapa cairan tinggal dalam pembuluh darah?
Dua pertiga dari cairan tubuh manusia berada di intraseluler. Ruang ekstraselular yang
tersisa dibagi menjadi plasma darah dan ruang interstitial. Kedua kompartemen
tersebut saling berhubungan melintasi lapisan pembuluh darah untuk pertukaran
elektrolit dan zat-zat gizi untuk metabolisme sel. Tekanan hidrostatik intravaskular
yang positif terus menerus memaksa darah ke ruang interstitial. Dalam kondisi
fisiologis, molekul besar, seperti protein dan koloid, tidak dapat melewati sawar
pembuluh darah dalam jumlah yang besar, yang merupakan hal yang utama untuk
fungsi dari sirkulasi. Jika tidak, tekanan hidrostatik intravaskular akan mengakibatkan
hilangnya kendali cairan ke ruang interstitial dan akhirnya akan menyebabkan edema
jaringan [1]. Pada tahun 1896, Ernest Starling mengatakan tekanan osmotik interstitial
harus berada di bawah tekanan pembuluh darah intraseluler. Konsentrasi gradien
melintasi lapisan dinding pembuluh darah menghasilkan aliran yang diarahkan ke
pembuluh darah dan membalikkan tekanan hidrostatik mengakibatkan filtrasi menjadi
rendah per unit waktu. Menurut prinsip Starling, lapisan sel endotel bertanggung
jawab untuk fungsi lapisan pembuluh darah [1]. Dalam percobaan model tikus
microvessel, telah ditunjukkan bahwa tekanan osmotik interstitial hampir 70% lebih
rendah dari tekanan osmotik intravaskular sehingga tidak menyebabkan edema
interstisial, yang tidak jauh berbeda dengan konsep Starling, yang menunjukkan
hanya peran kecil untuk konsentrasi protein interstitial [2]. Lapisan membrane endotel
glykokalik memainkan peran penting dalam konteks ini. Setiap endotel vaskular yang
sehat dilapisi oleh syndecans transmembran dan glypicans terikat membran yang
berisi heparan sulfat dan rantai samping kondroitin sulfat, yang bersama-sama
merupakan glikokalik endotel [3,4]. Protein terikat plasma, glikosaminoglikan

dilarutkan, dan Hyaluronan yang memuat glikokalik ke lapisan permukaan endotel

(ESL), yang merupakan subjek dari konstitusi periodik dan degradasi. Dalam kondisi
fisiologis, ESL memiliki ketebalan sekitar 1 mm dan mengikat sekitar 800 ml plasma
darah, sehingga volume plasma dapat dibagi menjadi sirkulasi dan non sirkulasi [4,5].
Dengan demikian, glikokalik tampaknya bertindak sebagai filter molekuler,
mempertahankan protein dan meningkatkan tekanan onkotik dalam lapisan
permukaan endotel. Sebuah ruang kecil antara dinding pembuluh anatomi dan ESL
selalu terdapat protein bebas [2]. Dengan demikian, cairan akan hilang ketika
melewati dinding pembuluh darah yang dibatasi oleh gradien tekanan onkotik dalam
ESL [6] Oleh karena itu prinsip klasik Starling 'dimodifikasi dengan "double-barrierkonsep" lapisan sel endotel dan lapisan dinding pembuluh darah [6].
Disfungsi Lapisan Pembuluh darah : Penyebab dan Akibat
ESL merupakan permukaan yang pertama kali dilewati antara darah dan jaringan dan
semua proses serta fungsi terjadi dilapisan pembuluh darah tersebut, seperti
peradangan dan sistem koagulasi. Sejumlah penelitian mengidentifikasi berbagai agen
dan negara patologis merusak perancah glycocalyx dan ketebalan ESL. Dalam model
hati babi, Chappell et al. menunjukkan 30 kali lipat peningkatan penumpahan heparan
sulfat setelah reperfusi postischemic [7]. Data ini telah disetujui oleh penyelidikan
klinis, yang menunjukkan peningkatan kadar plasma dari syndecan-1 dan heparan
sulfat pada pasien dengan iskemia global atau regional yang menjalani operasi besar
vaskuler [8]. Selain iskemia cedera / reperfusi, beberapa mediator beredar diketahui
memulai degradasi glikokaliks. Tumor necrosis factor (a), sitokin, protease, dan
heparanase dari sel mast diaktifkan secara aktor dalam sindrom respon inflamasi
sistemik yang mengarah ke pengurangan ketebalan ESL, yang memicu peningkatan
adhesi leukosit dan transendotel permeabilitas [7,9 baik dijelaskan, 10]. Menariknya,
hypervolemia juga dapat menyebabkan gangguan Glikokaliks dimediasi oleh
pembebasan atrial natriuretik peptida [11]. Hypervolemia akibat pemberian cairan
yang tidak cukup tinggi karena dapat menyebabkan kerusakan glycocalyx iatrogenik.
Seperti ditunjukkan dalam penelitian dasar, konsekuensi dramatis dari glycocalyx
dasar, yang kehilangan banyak kemampuannya untuk bertindak sebagai penghalang
kedua, sangat peningkatan permeabilitas transendothelial dan pembentukan berikut
edema interstitial [7,11]. Relevansi ini data eksperimen yang mengesankan digaris
bawahi oleh Nelson et al., Yang menemukan peningkatan kadar plasma dari

glikosaminoglikan

dan

syndecan-1

pada

pasien

septik,

sedangkan

tingkat

glikosaminoglikan median lebih tinggi pada pasien yang tidak bertahan [12].
Keseimbangan Cairan : Kemana cairan tersebut hilang ?
Secara fisiologis produksi urin dan cairan yang tidak dapat diperkirakan yang keluar
bisa digantikan dengan absorbsi air bebas yang berasal dari sistem gastrointestinal
namun akan memberikan efek yang kurang baik di ruang ekstravaskular, bila keadaan
defisiensi cairan tidak ditingkatkan. Secara fisiologis penggantian cairan pada orang
yang berpuasa akan terbatas, maka dari itu harus di kompensasi dengan pemberian
infus kristaloid. Komposisi dari cairan infus yang digunakan harus disesuaikan
dengan kondisi fisiologis untuk menghindari ketidakseimbangan asam basa, yang
memerlukan infus kristaloid yang seimbang. Dalam pembedahan, trauma atau syok
sepsis yang di sertai dengan kehilangan cairan (perdarahan, kebocoran plasma) akan
berdampak buruk terutama pada jaringan intravascular. Akibatnya yang pertama dari
kehilangan cairan tersebut adalah kehilangan cairan menurunkan distribusi
diintraseluler, interstisial, dan ruang intravaskular yang dimana secara perlahan akan
menyebabkan dehidrasi, sedangkan akibat yang kedua dehidrasi dapat menyebabkan
hipovolemia akut. Pada saat berpuasa dapat menimbulkan keadaan hipovolemia
seperti yang dijelaskan dalam buku teks anestesi [15,16], tidak bisa dijelaskan atau
disamakan dengan keadaan diatas karna hal tersebut terjadi secara fisiologis terjadi
dan tidak terjadi pada semua pasien [17]. Bahkan pada pasien yang melakukan
pembedahan ringan atau pembedahan non invasif dengan keadaan kardiovaskuar yang
baik pemberian cairan tidak begitu diindikasikan [17]. Perbedaan muatan cairan atau
perbedaan pemberian cairan dapat meningkatkan mediasi pembebasan atrial
natriuretic peptide yang menyebabkan degradasi glycocalyx sehingga meningkatkan
permeabilitas pembuluh darah, meningkatkan pembentukan edema jaringan hal
tersebut merupakan tahap awal dari kebocoran pembuluh darah dan kegagalan organ
[11,18]. Kehilangan cairan yang tidak dapat diperkirakan terkadang diberikan secara
berlebihan dari yang seharusnya , walaupun saat pembedahan laparotomy hanya
kehilangan cairan 1 ml / kg per jam [19]. Secara teori sebenar pemberian cairan yang
cukup seharusnya dapat menggantikan cairan yang hilang seperti yang dijelaskan
sebelumnya untuk mempertahankan volume darah normal pada pasien sakit kritis.
Berdasarkan asumsi bahwa pemberian cairan yang lebih banyak dari seharusnya
selama operasi tersebut dapat mencegah hipotensi dan gagal ginjal pasca operasi [20],

meskipun tidak adanya gagal ginjal setelah operasi [21]. Selanjutnya, infus kristaloid
profilaksis tidak mempengaruhi terjadinya hipotensi yang disebabkan oleh dilatasi
pembuluh darah [22]. Walau bagaimanapun menurut pertimbangan fisiologis pasien
memerlukan cairan intravena lebih dari yang disarankan. Berdasarkan volume darah,
operasi besar menyebabkan defisit cairan 3-6 liter selama operasi dalam [23,24].
Bahkan bertahan hingga 72 jam setelah trauma atau operasi [25]. Hal tersebut terjadi
karena adanya fenomena pertukaran cairan ke dalam ruang ketiga. Ruang ketiga ini
dapat dibagi menjadi "anatomi" dan "nonanatomi". Pertukaran cairan fisiologi dari
intervaskuler

menuju

ruang

interstitial

melintasi

dinding

pembuluh

darah

mengandung hanya sejumlah kecil protein. Ini tidak menyebabkan edema interstisial
selama dibantu oleh sistem limfatik yang baik. Perpindahan cairan ke "anatomi" ruang
ketiga didasarkan pada mekanisme ini, tetapi dalam jumlah yang patologis [13,14],
yang melampaui batas kapasitas dari sistem limfatik. Ruang ketiga nonanatomic,
sebaliknya, diyakini kompartemen terpisah dari ruang interstitial [13,14]. Ketika
cairan menuju kompartemen diasumsikan terjebak dan hilang untuk pertukaran
ekstraseluler. Hilangnya cairan ke nonanatomic ruang ketiga adalah akumulasi cairan
dari jaringan trauma, usus, atau rongga peritoneum [15,16], tetapi meskipun penelitian
intensif, ruang seperti tidak pernah diidentifikasi Cairan digeser dari intravaskular ke
ruang interstitial. Pergeseran cairan ini dapat diklasifikasikan menjadi dua jenis [13]:
Tipe 1, selalu terjadi dan fisiologis, pada saat pertukaran cairan hampir tidak ada
protein yang bebaskeluar.
Tipe 2, pertukaran cairan patologis disebabkan oleh disfungsi intravaskuler. Berbeda
dengan tipe 1, cairan melintasi pembuluh darah bersama protein [13]. Pergeseran ini
pada dasarnya memiliki tiga alasan. Pertama, manipulasi pembedahan meningkatkan
permeabilitas kapiler sehinggs protein berlebihan [26]. Cairan interstitial meningkat
sekitar 10% selama penyambungan pembuluh darah selama operasi [27]. Pemberian
kritaloid 5 ml / kg dua kali lipat kemugnkinan dapat menyebabkan edema. Kedua,
trauma merusak pembuluh darah mengakibatkan pengeluaran protein secara
berlebihan [7-10]. Ketiga, hypervolemia iatrogenik dapat menyebabkan Glikokaliks
degradasi dan menyebabkan pergeseran luas cairan dan protein ke jaringan [23,24].
Pergeseran patologis dapat mempengaruhi cairan infus. Berbeda dengan kristaloid,
koloid akan tinggal di dalam pembuluh darah, Rehm et al. dijelaskan volume-efek >
90% ketika pemberian tetrastarch diarsorpsikan dengan benar maka kehilangan cairan
volume intravaskular dapat diatasi. Diberikan bolus pada pasien normovolemic, dua

pertiga dari volume diserap sisanya akan keluar dari pembuluh darah [23,24]. Volume
resusitasi dengan koloid jelas membutuhkan titrasi yang baik, sehingga pada saat
kehilangan cairan kan menghindari perpindahan protein yang besar ke ruang
interstitial [14]. Berdasarkan double barrier concept, hypoproteinemia bahkan
mengintensifkan disfungsi menyebabkan disfungsi dari pembuluh darah dan
meningkatkan pembentukan edema jaringan. Perioperatif pergeseran cairan tercermin
dalam data klinis yang diterbitkan dua dekade lalu. Lowell et al. menunjukkan
kenaikan berat badan lebih dari 10% di > 40% dari pasien yang dirawat di unit
perawatan intensif setelah operasi besar. Peningkatan berat badan, yang mewakili
edema interstitial, berkorelasi kuat dengan kematian [28].
Dehidrasi atau Hipovolemia?
Dehidrasi, paling sering memberikan dampak buruk di ekstravaskuler, dan
hipovolemia akut adalah merupakan 2 diagnosa yang berbeda serta membutuhkan
terapi yang berbeda. Produksi urin dan kehilangan cairan yang tak bisa diperkirakan
menyebabkan kehilangan cairan, oleh karena terjadinya redistribusi diantara ruang
intravaskuler dan ekstravasluler, dan pada keadaan ini tidak merusak intravaskuler
secara langsung. Dengan itu dehidrasi harusnya di terapi dengan mengisi ruang
ekstravaskuler dan mengganti cairan yang hilang dengan pemberian kritaloid.
Sebaliknya pada keadaan hipovolemia akut akan memberikan dampak yang buruk
terhadap intravaskuler. Karena kristaloid bisa secara bebas terdistribusi di intrasitial
dan intravaskuler hal tersebut tidak dapat memenuhi volume resusitasi pada akut
hipovolemia. Hilangnya cairan dan protein akibat penurunan tekanan onkotik
intravaskuler, serta buruknya pemberian cairan koloid intravena yang berlebihan
dapat menyebabkan edema interstitial. Dengan itu cairan yang akan bertahan pada
vaskuler dan mempertahankan tekanan onkotik adalah kolloids yang dimana
diperlukan untuk terapi pada keadaan hilangnya plasma volume.
Cairan intravena: kristaloid dan koloid
Kristaloid
Kristaloid bebas mendistribusikan seluruh barrier vaskular. Hanya seperlima dari
jumlah intravena infus tetap intravascularly [15,16]. Dicanangkan buku teks, jumlah
empat kali lipat dari infus kristaloid diperlukan untuk mencapai efek volume yang
sebanding sebagai dicapai dengan pemberian koloid. Padahal ini benar jika

penghalang vaskular masih utuh, pada pasien yang menderita rasio kebocoran kapiler
dari hanya 1,6: 1 sampai 1: 1 (kristaloid untuk koloid infus) diamati untuk mencapai
efek setara [29,30]. Namun demikian, pengobatan koloid menghasilkan peningkatan
linear yang lebih besar dalam preload jantung dan output pada pasien hipovolemik
septik dan nonseptic dibandingkan dengan pemberian kristaloid [31], dan ekspansi
volume berlangsung lebih lama selama perdarahan akut eksperimental [32]. Meskipun
saat ini dibahas, mengenai konsep double-penghalang satu bisa berasumsi bahwa
koloid mendistribusikan hampir sebebas kristaloid di penghalang vaskular gangguan
serius. Namun, resusitasi volume dengan infus kristaloid dikaitkan dengan komplikasi
serius, seperti sindrom pernafasan distress, edema serebral, dan sindrom kompartemen
abdominal pada pasien dengan trauma besar [33-35] dan mempromosikan
pengembangan asidosis hiperkloremik [36]. Bahkan jika ada diskusi yang sedang
berlangsung tentang manfaat dan risiko dari larutan kristaloid seimbang, penggunaan
yang bermanfaat untuk menghindari gangguan asam-basa [25].
koloid
Satu-satunya koloid alami yang digunakan dalam hal klinis albumin. Koloid buatan
HES (HES) dan gelatin digunakan prevalently di negara-negara Eropa, sedangkan
albumin diterapkan kurang umum [37].
Albumin
Dalam kondisi fisiologis, albumin adalah molekul terutama bertanggung jawab untuk
tekanan osmotik intravaskular dan harus menjadi koloid yang ideal untuk
mengembalikan kerugian protein dari pembuluh darah. Namun, sebagai koloid alami,
albumin dapat menyebabkan reaksi alergi parah dan komplikasi imunologi. Tanggal
mengenai penggunaan albumin untuk mengobati hipovolemia terutama berasal dari
pasien sakit kritis. Sebuah Cochrane review 30 acak, percobaan terkontrol, termasuk
1.419 pasien dengan hipovolemia, menunjukkan tidak ada bukti untuk mortalitas
membandingkan albumin untuk kristaloid resusitasi volume. Penggunaan albumin
mungkin sebaliknya bahkan meningkatkan mortalitas [38]. Baru-baru ini, Studi
AMAN, termasuk 6.997 pasien dan membandingkan albumin normal saline resusitasi
cairan, ditemukan tidak efek menguntungkan atau mortalitas meningkat pada
kelompok albumin. Selain itu, tidak ada perbedaan di hari ventilasi mekanis atau
kebutuhan terapi ginjal pengganti yang diamati [39]. Dalam trast con untuk iso
albumin onkotik, yang tidak mempengaruhi hasil pasien sakit kritis, pengobatan

dengan hyperoncotic albumin peningkatan mortalitas [40]. Oleh karena itu, pemberian
albumin isooncotic dapat dibenarkan dalam kasus-kasus tertentu, tetapi tidak sebagai
strategi rutin untuk volume resusitasi.
Gelatin
Gelatin adalah polipeptida polydisperse dari terdegradasi sapi kolagen. Berat molekul
rata-rata dari solusi gelatin adalah 30.000 sampai 35.000 Da dan volume- mereka
memperluas kekuasaan sebanding. Beberapa studi telah meneliti keamanan
farmakologi dari gelatin. Singkatnya, semua persiapan dikatakan aman dalam hal
koagulasi dan integritas organ [15,16] kecuali fungsi ginjal. Mahmood et al.
menunjukkan tingkat yang lebih tinggi dari serum urea dan kreatinin sebagai
kerusakan tubular lebih jelas pada pasien yang diobati dengan larutan gelatin 4%
dibandingkan dengan HES (HES) solusi saat menjalani operasi aneurisma aorta [41].
Oleh karena itu, penggunaan gelatin terbatas pada pasien ginjal-gangguan.
Hidroksietil pati
Hidroksietil pati, polimer buatan, berasal dari amilopektin, yang merupakan rantai
bercabang molekul glukosa yang diperoleh dari jagung lilin atau kentang. Konservasi
dari degradasi dan kelarutan air yang dicapai oleh hydroxymethylation unit glukosa
solusi HES tersedia dalam beberapa persiapan dan bervariasi dalam konsentrasi, berat
molekul, substitusi molar, C2 rasio / C2, pelarut, dan profil farmakologis. Meskipun
molekul HES kecil (<50-60 kD) dieliminasi dengan cepat oleh filtrasi glomerulus,
molekul yang lebih besar yang dihidrolisis untuk pecahan kecil dan sebagian diambil
dalam sistem retikuloendotelial. Meskipun penyimpanan ini tampaknya tidak
mengganggu sistem gocytic yang mononuklear pha-, itu adalah luar biasa bahwa berat
molekul rendah HES terakumulasi kurang dibandingkan dengan HES berat molekul
tinggi [42]. Efek negatif dari HES molekul tinggi pada sistem koagulasi dijelaskan
dengan baik. Persiapan> 200 kD menyebabkan pengurangan von Willebrand factor
dan faktor VIII, menyebabkan adhesi platelet menurun. Persiapan berat molekul
rendah, seperti HES 130 / 0,4, hanya memiliki efek minimal terhadap koagulasi. HES
dalam larutan seimbang meningkatkan ekspresi platelet diaktifkan GP IIb / IIIa,
menunjukkan hemostasis ditingkatkan [43,44]. Berfokus pada fungsi ginjal, tingkat
80% dari "osmotik lesi nephrosislike" dan gangguan fungsi ginjal dilaporkan pada
penerima transplantasi ginjal setelah pemberian HES 200 / 0.62 untuk mati otak donor

organ [45,46]. Pada pasien septik, penggunaan 10% HES 200 / 0,5 berkorelasi dengan
insiden yang lebih tinggi dari gagal ginjal dibandingkan dengan kristaloid [47].
Diakui, HES diberikan tanpa memperhatikan kriteria eksklusi dan keterbatasan dosis
dalam penelitian ini. The pathomechanism kemungkinan gangguan ginjal oleh koloid
adalah induksi hiperviskositas urin dengan menanamkan agen hyperoncotic pada
pasien dehidrasi. Filtrasi glomerulus molekul hyperoncotic menyebabkan urin
hyperviscous dan hasil dalam stasis dari aliran tubular [48]. Peningkatan tekanan
onkotik plasma, terlepas dari asal-usul, diketahui menyebabkan gagal ginjal akut sejak
lebih dari 20 tahun [49]. Berdasarkan patogenesis ini, semua koloid hyperoncotic
dapat menyebabkan kerusakan ginjal, sedangkan solusi pati tetra isooncotic, seperti
6% HES 130 / 0,4, tampaknya tidak merusak fungsi ginjal [41,46]. Setelah
administrasi tingkat aplikasi yang sangat tinggi (sampai 66 liter dalam 21 hari) pada
pasien dengan cedera kepala berat, ada penurunan fungsi ginjal yang diamati [50].
Berbeda dengan hasil penelitian VISEP [47], studi SOAP, yang mencakup lebih dari
3.000 pasien septik sakit kritis diobati dengan pentastarch dan tetrastarch solusi, juga
menunjukkan risiko tidak lebih tinggi untuk gagal ginjal [51]. Hidroksietil pati
diberikan dalam jumlah yang jauh lebih rendah (13 vs 70 ml / kg) dan untuk jangka
waktu yang lebih pendek dalam studi SOAP. Ada bukti bahwa HES juga memodulasi
peradangan. Koloid sintetik menghambat adhesi neutrofil pada endotel dan neutrofil
infiltrasi paru [52,53].
Selanjutnya, HES dilemahkan respon inflamasi pada tikus septik serta pada tikus
volume yang diresusitasi dengan HES 130 / 0,4 pada syok hemoragik berat dengan
mengurangi tumor necrosis factor-alpha, interleukin, dan stres oksidatif [53,54].
Meskipun aspek menguntungkan dari penggantian volume dengan apa yang disebut
"modern" solusi tetrastarch isooncotic, khususnya dalam mencapai stabilitas
hemodinamik dini dipahami [31,32], data difokuskan, didukung memadai, calon uji
klinis membuktikan mereka hasil-relevansi diperlukan.
Tujuan dan strategi untuk penggantian volume
Karena tujuan utama dari sistem kardiovaskular adalah menyediakan jumlah oksigen
yang cukup ke tubuh dan kebutuhan metabolik untuk mempertahankan perfusi
jaringan yang memadai untuk memastikan oksigenasi jaringan. Hipovolemia, serta
hypervolemia,

dapat

mengurangi

oksigenasi

perfusi

jaringan

dan

dapat

mengakibatkan kegagalan organ [55-59]. Bahkan oksigen tambahan tidak dapat

meningkatkan oksigenasi di jaringan hipoperfusi [60]. Karena hipovolemia

merupakan penyebab tersering untuk ketidakstabilan hemodinamik pada pasien sakit
kritis, mengamankan volume intravaskular yang memadai adalah landasan
manajemen hemodinamik. Tapi bagaimana kita bisa menilai volume intravaskular
"memadai"? Pada keadaan yang sehat hubungan antara variabel hemodinamik sudah
cukup komplek, bahkan lebih kompleks dalam penyakit dan interpretasi mereka
memerlukan pemahaman yang kuat tentang cardio mekanisme regulasi vaskular.
Pada pasien hemodinamik tidak stabil, pada dasarnya empat pertanyaan fungsional
perlu dijawab. Karena tujuan utama resusitasi adalah untuk mengamankan oksigenasi
jaringan, pertanyaan pertama sudah yang paling menentukan, tetapi juga yang paling
sulit satu: Apakah oksigenasi jaringan yang memadai? Karena perwakilan oksigenasi
jaringan tidak dapat diukur secara langsung, terutama tiga variabel yang digunakan
sebagai pengganti: saturasi oksigen vena campuran; oksigenasi vena sentral; dan
laktat serum. Gunakan, interpretasi, dan signifikansi parameter ini mengenai penilaian
oksigenasi jaringan dibahas di tempat lain. Singkatnya, tidak satupun dari mereka
mampu mendeteksi jaringan kekuranga oksigen secara pasti, karena setiap orang
dipengaruhi oleh berbagai morbiditas dan interaksi obat [61-64]. Pertanyaan kedua
adalah: Bagaimana cardiac output (CO), sebagai determinate utama pengiriman gen
oxy, diperbaiki? Atau, lebih baik mewakili hal-hal klinis: Apakah volume pasien
responsif? Pertanyaan ketiga menganggap ada vasomotor: Apakah meningkat,
menurun, atau normal pada pasien hipotensi? Keempat, kerja jantung: Apakah jantung
bisa mempertahankan CO memadai ketika tekanan arteri dipulihkan tanpa kegagalan
[65]?
Biasanya dokter menjawab pertanyaan ini dengan mengukur tekanan brata-rata arteri
(MAP), tekanan vena sentral (CVP), dan dengan mengamati diuresis [66]. Semua
parameter ini mudah untuk mengukur, tapi sebenarnya tidak memungkinkan untuk
menilai ketidakstabilan hemodinamik cukup atau untuk membedakan penyebabnya
memadai. Jika penyakit menyebabkan penurunan CO, reaksi fisiologis tubuh,
dimediasi oleh baroreseptor, adalah untuk mengembalikan penurunan tekanan arteri
untuk menjaga tekanan perfusi serebral [67]. Hal ini sering disertai dengan takikardia,
disebabkan oleh modulasi nada simpatik. Oleh karena itu, hipotensi mencerminkan
kegagalan mekanisme kompensasi ini, sedangkan normotensi tidak secara otomatis
menjamin stabilitas hemodinamik [68]. Selain itu, takikardia dan hipotensi dapat
absen selama syok hipovolemik sampai intra penyusutan volume vaskular mencapai

20% atau lebih [69,70]. CVP menunjukkan korelasi volume darah [71], tidak
memadai untuk mendeteksi hipovolemia andal, dan terutama tidak bisa merasakan
utang output dan jaringan oksigen jantung menurun dalam keadaan awal. Selanjutnya,
perubahan CVP setelah pemberian volume yang tidak memungkinkan kesimpulan
perubahan stroke volume (SV) atau cardiac output (CO) [72]. Mengukur CVP karena
itu tidak memadai untuk menilai hemodinamik pasien dan untuk mengelola resusitasi
volume. Karena CO adalah determinate utama dimana oksigen terse- but tion ke
jaringan bervariasi untuk menyesuaikan kebutuhan metabolik, efektivitas terapi
resusitasi dapat dievaluasi terbaik dengan pemantauan terus menerus dari cardiac
output. Beberapa metode yang berbeda, mulai dari teknik pengenceran indikator
klasik kurang pendekatan invasif, seperti analisis kontur pulsa arteri dan teknik
Doppler, secara klinis tersedia. Sebuah penjelasan rinci dan diskusi keuntungan
masing-masing dan kerugian adalah di luar lingkup artikel ini dan dapat ditemukan
dalam tinjauan baru-baru ini [73,74]. Teknik pemantauan meja Sui untuk
mendefinisikan strategi pengobatan dapat menilai cardiac output serta preload jantung
dan, pertama-tama, untuk memprediksi respon volume pasien, yang sebagian besar
berlaku untuk parameter volumetrik dan fungsional memanfaatkan interaksi jantungparu di bawah mekanik ventilasi [75-78]. Di masa lalu, berbagai penelitian yang
diterbitkan yang disukai konsep individu strategi manajemen volume perioperatif.
Kebanyakan dari mereka berasal dari perawatan perioperatif dan difokuskan terutama
pada pengobatan di ruang operasi. Tentu saja, strategi tersebut berdampak perawatan
ICU pasca operasi juga. "Membatasi" strategi dibandingkan dengan "permisif" atau
"liberal" yang. Namun, yang diterima secara umum definisi dari "membatasi" atau
"liberal" strategi cairan tidak ada, membuat mereka hampir tak tertandingi studi.
Penyidik biasanya berlabel rejimen cairan standar mereka tradisional "standar"
kelompok dan membandingkannya dengan membatasi Model pemberian cairan
mereka sendiri. "Liberal" di salah satu studi sudah "ketat" di sidang lain dan
pemberian cairan diikuti skema kaku atau tujuan yang berbeda. Selain itu, titik akhir
dari studi yang diberikan bervariasi dari muntah pasca operasi, nyeri, atau oksigenasi
jaringan ke usus waktu pemulihan, yang de facto aturan keluar perbandingan [79-82].
Salah satu studi yang paling dikutip dalam hal ini adalah karya Brandstrup et al., Yang
menunjukkan bahwa pembatasan cairan perioperatif (2740 vs 5388 ml) mengurangi
kejadian kebocoran anastomosis, edema paru, pneumonia, dan infeksi luka di 141
pasien yang menjalani bedah kolorektal besar tanpa meningkatkan tingkat kegagalan

ginjal. Menariknya, melihat lebih dekat pada protokol infus mengungkapkan

perbandingan antara kristaloid dibandingkan pemberian cairan koloid. Kelompok
membatasi diterima terutama koloid, sedangkan kelompok liberal diperlakukan secara
eksklusif dengan kristaloid [79]. Semua dari mereka studi memiliki kesamaan yang
ada gol hemodinamik yang ditetapkan, yang berbeda dengan "tujuan-diarahkan terapi
(GDT) pendekatan" yang dikenal paling menonjol dari penelitian oleh Rivers et al.,
Di mana penulis menggunakan vena sentral tekanan, tekanan arteri rata-rata, laktat
serum, dan saturasi oksigen vena campuran sebagai tujuan untuk mengoptimalkan
pengobatan dini pada pasien septik [83]. Peri lanjut dan studi pasca operasi pada
pasien bedah menggarisbawahi pentingnya tujuan hemodinamik "fungsional" untuk
meningkatkan hasil pasien. Dalam meta-analisis membungkus empat calon percobaan
acak, cardiac output dipandu cairan manajemen berkurang tinggal di rumah sakit dan
berkurang tingkat komplikasi [84]. Selain itu, interleukin-6 respon dilemahkan dalam
studi bedah kolorektal menggunakan tujuan-diarahkan manajemen cairan Dopplerdioptimalkan [85]. Gopfert et al. melaporkan mengurangi waktu ventilasi mekanik
dan unit perawatan intensif tinggal pada pasien bedah jantung menggunakan indeks
volume akhir diastolik global dan curah jantung untuk mengelola administrasi Volume
[86]. Indeks air paru ekstravaskuler mungkin menjadi alat yang berguna untuk GDT,
juga, dan subyek diskusi saat [87]. Selanjutnya, terapi cairan diarahkan pada tujuan
mengurangi peradangan, morbiditas, dan mortalitas tidak hanya di sepsis berat dan
syok septik, tetapi juga pada pasien yang menjalani operasi besar [88-90].
Kesimpulan
Temuan konsolidasi mengenai lapisan permukaan endotel menyebabkan pemahaman
baru dari penghalang vaskular. Prinsip jalak 'itu disesuaikan dengan "konsep doublepenghalang" dan mekanisme ESL perubahan pada pasien sakit kritis tampaknya
memainkan peran utama dalam pembentukan edema jaringan. Karena glycocalyx
penurunan mengarah ke permeabilitas kapiler meningkat, kehilangan cairan ke ruang
interstitial, umumnya dianggap sebagai kerugian terhadap "ruang ketiga," adalah salah
satu konsekuensi utama dari degradasi ESL. Dies murid tentang cairan dan terapi
volume yang membuktikan efek buruk dari pembentukan edema jaringan pada fungsi
organ dan kematian. Oleh karena itu, pengetahuan tentang konsekuensi dari
menanamkan berbagai jenis kristaloid dan koloid selama negara fisiologis dan
patologis diperlukan. Selanjutnya, cairan dan administrasi Volume dua terapi yang

berbeda untuk dua diagnosis yang berbeda. Dehidrasi disebabkan oleh hilangnya
urine, puasa pra operasi, dan keringat insensible membutuhkan pemberian cairan
terutama didasarkan pada infus kristaloid. Defisit intravaskular volume, yaitu,
hipovolemia akut, sehingga curah jantung menurun membutuhkan penggantian
volume, di mana administrasi koloid muncul berarti, meskipun data klinis saat ini
tidak akhirnya konsisten. Jumlah yang tepat volume diberikan harus dititrasi "tujuan
diarahkan" menggunakan strategi berdasarkan parameter makro-hemodinamik aliran
dan volume.
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