Traduccion Neurointensivismo Fluidoterapia en Paciente Neurocritico
Traduccion Neurointensivismo Fluidoterapia en Paciente Neurocritico
Traduccion Neurointensivismo Fluidoterapia en Paciente Neurocritico
13.1 Introduction
The management of intravenous fluids in neurocritical patients plays an important role
in the evolution and prognosis of acute brain injury. There is no clear consensus on what
type of solution or at what stage of neurological disease fluid therapy should be initiat-
ed. Parameters extrapolated from studies on less neurocritical conditions provide only
an approximation to the pathophysiology of acute brain injury.
This chapter develops general concepts in the management of water and electrolyte
metabolism in the central nervous system, describes parenteral solutions commonly
used in neurocritical care, and assesses their respective strengths and weaknesses.
The infusion of parenteral solutions may influence the development of cerebral ede-
ma [1], and the infusion of hypotonic fluids is reported to decrease plasma osmolari-
ty, with the subsequent development of cerebral edema. Insofar as these observations
may have been accurate, there was the widely held misconception that we should “re-
strict fluid intake” in the acute neurological patient to prevent intracranial hypertension
[2]; however, fluid restriction also carries the risk of hypovolemia, hypotension and de-
creased cerebral perfusion pressure, a triad which favours the development of cerebral
ischemia [3-6].
Water is the most abundant component of the body and accounts for 60-80% of body
weight depending on age, sex, and body fat content. About half (50-60%) is distributed
as intracellular water, the rest as extracellular water (38-45%), with the remaining small
fraction as transcellular water.
With few exceptions, the cell membrane is permeable to the passage of water through
an osmotic gradient. Osmolarity refers to the concentration of solutes in a solution; the
osmotic gradient is the pressure difference between two solutions, wherein a solvent
will move from a solution of lower to a solution of higher osmolar concentration, bring-
ing it, the water in this example, to a higher osmolarity equal on both sides of the gra-
dient.
Intracellular anions are macromolecules which do not diffuse across membranes; they
attract large numbers of cations, the main one being potassium (K+). Conversely, extra-
cellular anions are small, and the major cation is sodium (Na+). Cellular homeostasis is
maintained by Na/K AT pumps that prevent cells from bursting. The other factor regulat-
ing cell volume is the osmolarity of the extracellular space [7].
The brain is highly sensitive to changes in homeostasis. A state of hyponatremia leads to
an increase in cell volume, resulting in cerebral edema, whereas hypernatremia leads to
cellular dehydration, with shrinkage of the brain parenchyma [8].
Importantly, some molecules are ineffective osmoles (ethanol, urea): they can increase
the concentration of solutes in the extracellular space but do not cause water move-
ment across a membrane. In contrast, effective osmoles such as hypertonic saline so-
lutions attract water from the intracellular to the extracellular space by increasing the
osmolarity [9]. For this reason, we use the term “tone” when referring to the effective
osmolarity of a solution.
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Tone is important in evaluating hyponatremic states which can be classified as: isotonic
when the loss of Na+ equals that of water; hypotonic when the loss of Na+ is greater than
that of water; and hypertonic when the loss of water is greater.
Control of osmoregulation is important because it involves the interaction between the
kidney and the thirst mechanism through the antidiuretic hormone (ADH). This system
is so sensitive that changes in serum osmolality of 1-2% can activate or inhibit it, while
larger volume changes (8-10%) are required to activate the thirst mechanism and the re-
lease of ADH [10,11].
Fluid administration in neurocritical patients presents major challenges, including main-
taining adequate cerebral perfusion pressure (CPP), while avoid hyperglycemia and con-
trolling body temperature.
Preservation of CPP requires the maintenance of normovolemia without adversely af-
fecting intracranial pressure [12]. Several physiological principles must be considered: in
the peripheral tissues the capillaries of the membranes are highly permeable to water,
ions and other low-molecular-weight molecules, but limit the movement of high-mo-
lecular-weight substances such as albumin. In these tissues, the distribution of fluid be-
tween plasma and interstitial fluid volume is regulated by oncotic pressure gradients. In
contrast to the systemic capillary membranes, the brain capillary membranes constitut-
ing the brain blood-barrier (BBB) are impervious to most hydrophobic solutes, including
sodium [13]. Acute changes in plasma sodium, however small, generate a significant os-
motic pressure gradient of water movement that can bring about changes in the brain,
with important clinical manifestations [14].
13.2.1 Crystalloids
Isotonic crystalloid solutions (0.9% saline solution, Lactated Ringer) are inexpensive,
nontoxic, safe and non-reactive (Table 13.1). Usually, in conditions where vascular per-
meability is involved, only one third of the administered volume remains in the intravas-
cular space, significantly increasing the interstitial fluid; therefore, large volumes are re-
quired to overcome a particular hemodynamic situation, which can lead to a state of
shock or poor progression of resuscitation [15,16]. In patients with impaired capillary
permeability, a volume ratio from 1/7 to 1/10 per liter can be administered (of which
only 100 ml remain in the intravascular space). Other negative effects associated with
isotonic crystalloids are the development of tissue edema, acute renal failure and ab-
dominal compartment syndrome (ACS), as may occur with aggressive resuscitation with
large volumes [17-19].
Large volumes of saline (0.9% saline) may cause hyperchloremic acidosis; large volumes
of Lactated Ringer’s solution can cause plasma hypotonicity, leading to hyperlactatemia
without acidosis. Several studies have reported a pro-inflammatory effect of Lactated
Ringer’s solution (caused by the structure of the D-isomer) [20,21].
Hypertonic crystalloid solutions (3%, 7.5%, 23%) have a high sodium concentration and
exert a great effect as volume expanders. They expand the extracellular space very effec-
tively, reducing the tissue water; they also have a slightly positive inotropic effect and
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Composition per
Plasma Saline solution 0.9% Lactated ringer Observation
liter
Osmolarity 290 308 273 Isotonic?
Sodium (mEq) 140 150 132 Physiological?
Chlorine (mEq) 100 150 109
Potassium (mEq) 4 0 4
Calcium (mEq) 4.6 0 3
Lactate (mMol) 1 0 28
Table 13.1. Isotonic crystalloid solutions.
more than 48 h. Levels >160 mmol/l increase the risk of seizures. Monitor plasma os-
molarity.
Discontinuation of therapy with SSH:
• It is difficult to establish the time when therapy should be discontinued. In general
one must take into account the presence of intracranial hypertension and the risk of
hyponatremia.
• When considering completion of SSH therapy, leakage can be reduced by half every
6 h as it takes <20 ml/h to complete. During discontinuation of SSH therapy, serum
sodium should be monitored every 12 h. If levels increase or decrease more than ex-
pected, they should be checked more frequently.
• General management depends on the state of hydration, electrolyte levels and the
patient’s clinical condition. After completing SSH therapy, serum sodium monitoring
should not be different than in other critically ill patients [26,27].
13.2.2 Colloids
Colloid solutions produce higher plasma expansion and remain in the intravascular
space longer than crystalloids, with increased oncotic pressure and availability of oxy-
gen to the tissues. Animal studies have shown that some of these solutions improve mi-
crocirculation rheology. The goals of resuscitation are achieved in less time and with less
volume [28-30].
Albumin (natural colloid) is produced by the liver and is responsible for 80% of plasma
oncotic pressure, but remains intravascular for 24 hours; the volemic effect should not
last more than 4 hours. Albumin’s ability to hold water is determined by both its quan-
tity and the plasma volume loss that has occurred. One gram of albumin increases plas-
ma volume approximately 18 ml, and 100 ml of 25% albumin increases plasma volume
about 47 ml on average.
Undesirable effects have been described:
• Occurrence of hypocalcemia.
• Altered coagulation and inhibited platelet function.
• Presents pro-inflammatory properties.
• Facilitates the formation of edema if capillary leakage is present.
• Possibility of anaphylactic reactions (0.01%).
Its use in resuscitation is controversial and a large (SAFE) trial showed no differences
with crystalloids in the resuscitation of critically ill patients [31]. In a post hoc analy-
sis based on patients with severe traumatic brain injury who had entered into the SAFE
study, resuscitation with albumin was associated with higher mortality than resuscita-
tion with saline (41.8 versus 22.2%, respectively) [32].
Dextrans are monoquaternary polysaccharides which are seldom used because of their
side effects: mainly altered coagulation (reduced factor VIII); altered blood group typ-
ing has been described; risk of obstructive nephropathy; possible anaphylactic reactions
(0.27%) [29,30,33].
Gels (polygeline, modified oxypolygeline, melted gelatin). Derived from bovine colla-
gen, they are iso-oncotic and have less expansion power, which is why they are being
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abandoned. Brief expanding effect (2-3 h). Do not alter blood grouping or coagulation or
platelet adhesiveness. Do not accumulate in the body and do not affect the kidney. Ana-
phylactic reactions (0.34%) [29].
Hydroxyethyl starch (HES) is currently the most widely used synthetic colloid. Derived
from ethoxylated amylopectin from corn, this molecule is similar to glycogen, lending it
interesting features since the body does not recognize it as foreign matter. According to
their molecular weight and degree of hydroxiethylation, they vary in lifetime and vole-
mic effect (Table 13.4). The most recent have minimal side effects. Large volumes can be
used to achieve enhanced expandability; retention in the intravascular space is 4-6
hours. Improve blood rheology and microcirculation, do not have pro-inflammatory
properties, and effects on coagulation are negligible. Low incidence of anaphylactic re-
actions (0.05%). Produce less edema than crystalloids and remain longer in the intravas-
cular space [20,24,34,35].
The most important considerations when using a specific colloid are: the probability of
anaphylactoid reactions; the tendency to increase bleeding; the development of tissue
edema; renal involvement; and how the colloid affects immune response. Accordingly,
starches between 100-200 MW would be the most suitable colloids [36].
13.2.3 Mannitol
Mannitol, a six-carbon sugar, has been used for over half a century and is a mainstay
in medical treatment for cerebral edema and reducing intracranial pressure. Solutions
are available in 20 and 25%, with an osmolarity of 1098 and 1375 mOsm/l, respective-
ly. It is not metabolized and is excreted unchanged in urine [37]. Under normal condi-
tions, mannitol cannot cross the intact BBB, but when the BBB is impaired or with re-
peated doses, it may accumulate in the interstitium and the normal blood-brain gradient
is reversed, thus worsening cerebral edema [38]. Mannitol reduces ICP by the following
mechanisms:
• Produces expansion of plasma, decreasing blood viscosity and hematocrit, thus in-
creasing cerebral blood flow and delivery O2. This action is more marked when the
CPP is <60 mmHg [39-41].
• The osmotic effect facilitates the drainage of cerebral edema. This effect starts about
15-30 min after administration and lasts for at least 1.5-6 h depending on the clinical
condition. This effect persists but needs an intact barrier.
• Improves cerebral perfusion by improving blood rheology [42].
• Normal cerebral blood flow is maintained despite the reduction in vessel diameter
(reflex vasoconstriction). There is a decrease in cerebral blood volume and therefore
ICP decreases. For this mechanism to work properly, the autoregulation mechanism
must be intact.
• Mannitol also has antioxidant effects, but the contribution of this mechanism is not
clear.
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Side effects associated with the use of mannitol include pulmonary edema, cardiac fail-
ure, headache, nausea, vomiting, dehydration, rebound edema, electrolyte disorder
and acute tubular necrosis [38,41].
PPC Management
The reduction in ICP in patients with acute severe traumatic brain injury was original-
ly the only parameter considered in the management of HEC and the prevention of
secondary ischemia. Later, clinical observations focused on CPP, a variable derived by
subtracting the value of ICP from mean arterial pressure [5,6,12]. While recent stud-
ies have shifted the focus to CPP management, it is clear that current clinical practice
and guideline recommendations advise increasing blood pressure to maintain a CPP
above a “critical threshold” in the treatment of patients with acute brain injury [49-
51].
A CPP of 60 mmHg appears sufficient to limit secondary injury, but it is not devoid of the
risk of regional cerebral ischemia. Hypo-osmolality and hypovolemia are harmful and
patients should be kept normovolemic by avoiding the use of hypotonic fluids [52]. Ini-
tially saline 0.9% it can be used, but concentrations of SSH may vary according to each
individual case.
Management of Vasospasm
Volume expansion in subarachnoid hemorrhage (SAH) has two major functions: to pre-
vent clinical vasospasm and in acute intervention when clinical symptoms of vasospasm
manifest [53]. The clinical effectiveness of volume expansion and improvement of he-
modynamics in the treatment of cerebral vasospasm has been explained physiologically
by increased CBF in response to increased CPP [54].
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SSH Mannitol
• Prehospital? • Diffuse injury
• Patients with inadequate resuscitation, • Euvolemic patient with adequate volume
hypovolemia resuscitation
• Need to use small volumes • Osmolarity <320 mOsm/l
• CPP/TAM low at the expense of low • CPP low at the expense of elevated ICP
• hyponatremia • Intact autoregulation
• Need for continuous osmotic infusion therapy • Bolus continuous infusion useful
• Refractory to manitol
Table 13.5. Uses of SSH and mannitol.
CPP = Cerebral perfusion pressure TAM = ?
ICP = Intracranial pressure
Overload-induced hypertension was one of the first therapies used for treatment of va-
sospasm in patients with SAH. Subsequently, improved neurologic outcomes were re-
ported in patients treated with volume expansion, hemodilution and induced hyperten-
sion (triple-H therapy) [55,56].
13.4 Conclusions
Proper patient care is based on neurocritical assessment of neurological symptoms and
neuromonitoring findings coupled with close monitoring of hemodynamic status in or-
der to minimize secondary neuronal injury.
Currently, there is no magic bullet in the management of fluids in the critically patient,
and it seems unlikely that a protocol will meet all requirements for all patients and dif-
ferent levels of resuscitation.
Fluid resuscitation with either crystalloids or colloids is generally safe and effective in
critically patients, but these agents may be potentially beneficial (e.g., sepsis) or po-
tentially harmful (e.g., head injury) in certain patient populations. Modern fluid resus-
citation protocols should be designed to minimize complications and secondary insults
related to water therapy. Management of the neurological patient volume (as in all crit-
ically patients) should be based on a triad note:
• Fluid management.
• Type of patient.
• Goals and objectives.
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