13

Fluid Therapy in Acute Brain Injury

Gustavo Piñero 1
Neurological Intensive Care Coordinator. Intensive Therapy Service for Acute Municipal Hospital
1

“Dr.Leonidas Lucero”, Bahía Blanca, Argentina

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 Fluids Commonly Used in Neurocritical Care

Fluids commonly used in neurocritical care can be grouped into crystalloids (isotonic
crystalloids, and hypertonic crystalloids) and colloids (natural colloids (albumin), and ar-
tificial colloids (gelatins, dextrans and starches).

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.

decrease peripheral resistance [3,20,22,23]. The interest of these solutions in neurocrit-

ical care lies in their effects on cerebral hemodynamics by improving cerebral blood flow
(CBF) and decreasing intracranial pressure (ICP). The mechanisms of action for these so-
lutions are described in Table 13.2.
Their importance resides in their ability to expand with a small volume, but their effects
are transient: increased diuresis and natriuresis, reduced cell swelling, including endo-
thelial, and improved microcirculation [24].
However, their use can lead to hyperosmolarity, hyperchloremic acidosis, volume over-
load, renal failure, cerebral hemorrhage, pontine myelinolysis, hypernatremia and hy-
pokalemia [25].
They can be given as a continuous infu-
sion or bolus. A concentration of 2% can Mechanism of action Effect
be given by the peripheral route; how- Osmotic • Reduces brain water
ever, solutions with a concentration ≥3% content
may cause local irritation and local tissue • Reduces the mass effect
damage. • Prevents or treats
Practical aspects in the administration of elevated ICP
hypertonic crystalloids are the following: Hemodynamic • Increases TAM and CPP
• The rate of complications is low with • Improves organ
perfusion
close monitoring of serum sodium.
(Keep Na+ 145-155 mEq/l, serum os- Vasoregulation  • Optimizes cerebral
molarity <320 mOsm/l). perfusion
• Prevents or treats
• They are given with an infusion pump.
elevated ICP
Caution is warranted since they are
Immunomodulation • Modulates
not compatible with all medications,
inflammatory response
including some that are compatible • Reduces secondary
with 0.9% saline. Avoid administering injury
medications and transfusions with hy- Neurochemical • Normalizes neuronal
pertonic saline (SSH). membrane potentials
• General care: control the hydration • Limits neurochemical
status and assess the infusion accord- changes secondary to
ing to age (greater risk of complica- injury
tions in the elderly). Hypernatremic  • Prevents and treats
• Laboratory monitoring: Check serum hyponatremia
sodium every 6 h. In patients with Na+ Table 13.2. Mechanisms of action of hypertonic
levels <160  mmol/l there is a higher crystalloid solutions.
risk of renal failure, pulmonary edema CPP = Cerebral perfusion pressure
and heart failure. The problem is great- ICP = Intracranial pressure
er if the levels remain elevated for
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Composition per liter Plasma SSH 3% SSH 7.5% 23%

Osmolarity 290 1016 2586 7790
Sodium (mEq) 140 513 1293 3933
Table 13.3. Mechanisms of action of hypertonic 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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HES HES HES HES 200/0.5 HES 450/0.7

70/0.5 130/0.4 200/0.5 (Pentastarch) (Hetastarch)
Concentration (%) 6 6 6 10 6
Volemic effect (h) 1-2 3-4 3-4 3-4 5–6
MW (average) Daltons 70,000 130,000 200,000 200,000 450,000
Maximum dose (ml/kg) 33 30-50 33 20 20
Table 13.4. Characteristics of hydroxyethyl starch (HES).

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].

13.3 Use of Fluids in Neurocritical Care

13.3.1 Hemodynamic Management
Initial Resuscitation
In the early care of neurocritical patients, a set of general measures should be initiated
to achieve hemodynamic stability and an adequate oxygen supply with the aim to lim-
it or prevent secondary brain injury. Cerebral ischemia is considered the central mech-
anism of secondary damage. Clinical studies have shown that hypoxia and hypotension
are associated with poor prognosis [12,23,43,44]. The choice of fluid for maintaining
normovolemia plays a role in the treatment of acute brain injury.
Normal blood pressure should be achieved or maintained as soon as possible, based on
fluid administration and eventually with vasopressors. We recommend the administra-
tion of fluids to prevent or limit the time the patient is hypotensive [43]. Most prehospi-
tal crystalloid solutions are isotonic hypertonic solutions, which have been used in some
smaller studies with or without the association of colloids [45].
The initial objectives of water management should be: maintenance of adequate circu-
lating blood volume, a slightly decreased cerebral interstitial volume, and a tendency to
serum hyperosmolarity [46].
The administration of glucose solutions in these patients is not recommended, unless
there is a risk of hypoglycemia because hyperglycemia may exacerbate ischemic injury
[47,48].

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].

13.3.2 Osmolar Therapy in the Management of Cerebral Edema

The proper treatment of cerebral edema, and hence of increased ICP, improves cere-
bral perfusion and reduces mechanical damage caused by tissue compression. The goal
of therapy is the reduction of osmolar brain water and limiting secondary brain injury.
In the management of cerebral edema secondary to cerebral hypertension, the appro-
priate use of intravenous solutions and monitoring the internal environment are main-
stays in the treatment and prognosis of brain injury, because it is important to know the
benefits and likely side effects of the solutions commonly used in the treatment of this
disease.
Initial water resuscitation with crystalloid solutions should be performed while strictly
monitoring the plasma concentrations of sodium since hyponatremia is associated with
worsening of brain edema. The use of hypotonic fluids is contraindicated, as is the use
of dextrose solutions given the risk of hyperglycemia and its deleterious effects on the
injured brain [47,48].
Many studies have compared mannitol with SSH. The reality is that we understand there
are differences between the two substances that make them useful in different stages of
brain injury. Table 13.5 compares the best use of both these substances [57-60].

13.3.3 Changes in Na+ and Body Water

Patients usually present neurocritical water balance disorders; this is particularly but not
exclusively the case in patients with SAH. The incidence of hyponatremia depends on
the threshold for diagnosis (Na+ <135 mmol/l) is common in neurological patients and is
particularly associated with SAH, severe head trauma and meningitis. The causes of hy-
ponatremia are numerous, but the syndrome of inappropriate of antidiuretic hormone
(SIADH) secretion or the cerebral salt-wasting syndrome (CSW) occurs more frequently
in neurocritical patients [61,62]. In addition, administration of hypotonic fluids is a com-
mon cause of iatrogenic hyponatremia [63]. The close monitoring of urine output, lev-
els of nitric oxide in blood and urine and intravascular volume are of vital importance to
the most appropriate choice of fluid for every situation.
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Hypernatremia is defined as a serum sodium concentration >145 mmol/l; it is common

in critically patients and is often an indicator of disease severity or underlying process.
Hypernatremia is usually associated with water deficit, due to either inadequate fluid in-
take or excessive loss.

13.3.4 Therapeutic Hypothermia

The therapeutic use of hypothermia in neurocritical patients as a neuroprotective thera-
py has gained interest in recent years after the encouraging results found in post-cardiac
arrest patients [64,65]. Owing to the complexities of neurocritical patients, the promis-
ing results obtained experimentally have not been seen in clinical practice; nonetheless,
hypothermia is used by many neurological intensive care facilities.
Intravenous infusion of large cold volumes (4 °C) is one of the more conventional tech-
niques for inducing hypothermia. This method has been successfully used in studies of
patients with sudden death. Although it rapidly decreases body temperature, the meth-
od has several contraindications associated with the massive infusion of fluids [66]. The
most commonly used fluids are 0.9% saline or lactated Ringer’s solution, calculated at a
dose of 30-40 ml/kg.

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.

References
1. Shapira Y, Artru AA. Brain edema and neurologic status with rapid infusion of 0.9%
saline of 5% dextrose after head trauma. J. Neurosurgery Anesthesiol 1995; 7:
17‑25
2. Shenkin HA, Bezier HS, and Bouzarth WF. Restriction of fluid intake. Rational man-
agement of neurosurgical patient. J Neurosurg 1976; 45: 432-9
3. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in
determining outcome from severe head injury. J Trauma 1993; 34: 216-22
312
Fluid Therapy in Acute Brain Injury

4. Schmoker J, Zhuang J, Shackford S. Hemorrhagic hypotension after brain injury

causes an early and sustained reduction in cerebral oxygen delivery despite nor-
malization of systemic oxygen delivery. J Trauma 1992; 32: 714-9
5. Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion: management protocol and
clinical results. J Neurosurg 1995; 83: 949-62
6. The Brain Trauma Foundation, American Association of Neurological Surgeons,
Joint Section on Neurotrauma and Critical Care. Hypotension. J Neurotrauma 2000;
17: 591-5
7. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational approach to perioperative
fluid management. Anesthesiology 2008; 109: 723-40
8. Cooper D. Salines, Osmoles and Albumin. Critical Care and Resuscitation 2005; 7:
177-80
9. Weil MH, Henning RJ, Puri VK. Colloid oncotic pressure: clinical significance. Crit
Care Med 1979; 7: 113-6
10. Paczynsky R. Osmotherapy: Basic concepts and controversies. Critical Care Clinics
1997; 13: 105-32
11. Grocott MP, Mythen MG, Gan JT. Perioperative fluid management and clinical out-
comes in adults. Anesth Analg 2005; 100: 1093-106
12. Robertson CS. Management of cerebral perfusion pressure after traumatic brain
injury. Anesthesiology 2001; 95: 1513-17
13. Grande PO, Asgeirsson B, Nordstrom CH. Physiologic principles for volume regula-
tion of a tissue enclosed in a rigid shell with application to the injured brain. J Trau-
ma 1997; 42: S23-S31
14. Zornow MH, Todd mm, Moore SS. The acute cerebral effects of changes in plasma
osmolality and oncotic pressure. Anesthesiology 1987; 67: 936-41
15. Mcltlew D, Stephen C. Solutions for volume resuscitation in trauma patients. Curr
Opin Crit Care 1999; 5: S23-S28
16. Bellomo R, Morimatsu H, French C et al. The effects of saline or albumin resusci-
tation on acid-base status and serum electrolytes. Crit Care Med 2006; 34: 2891-7
17. Chappell D, Jacob M. A rational approach to perioperative fluid management Anes-
thesiology 2008; 109: 723-40
18. Balogh Z, McKinley BA, Cocanour CS, et al. Secondary abdominal compartment
syndrome is an elusive early complication of traumatic shock resuscitation. Am J
Surg 2002; 184: 538-43
19. Bagshaw S, Bellomo R. The influence of volume management on outcome. Curr
Opin Crit Care 2007; 13: 541-8
20. Boldt J. Do plasma substitutes have additional properties beyond correcting vol-
ume deficits? Shock 2006; 25: 103 -16
21. Holte K, Sharrock NE, Kehlet H. Pathophysiology and clinical implications of periop-
erative fluid excess. Br J Anaesth 2002; 89: 622-32
22. Soteras I, Fácil JM, Capella E, et al. Revisión bibliográfica sobre el empleo de suero
salino Hipertónico. Emergencias 2006; 18: 72-8
23. Shackford SR, Bourguignon PR, Wald SL, et al. Hypertonic saline resuscitation of
patients with head injury: a prospective, randomized clinical trial. J Trauma 1998;
44: 50-8
313
 Intensive Care in Neurology and Neurosurgery

24. Maier S, Holz-Hölzl C. Microcirculatory parameters after isotonic and hypertonic

colloidal fluid resuscitation in acute hemorrhagic shock. J Trauma 2009; 66: 337-45
25. Ogden A, Mayer S, Connolly E. Hyperosmolar agents in neurosurgical practice: the
evolving role of hypertonic saline. Neurosurgery 2005; 57: 207-15
26. White H, Cook D, Venkatesh. The use of hypertonic saline for treating intracranial
hypertension after traumatic brain injury. Anesth Analg 2006; 102: 1836-46
27. Johnson AL, Criddle LM. The salt indications for and implications of using hyperton-
ic saline. Critical Care Nurse 2004; 24: 36-48
28. American Thoracic Society. Evidence-based Colloid Use in the Critically Ill: Amer-
ican Thoracic Society Consensus Statement. Am J Resp Crit Care Med 2004; 170:
1247-59
29. Mora R, Ruiz A, Abraham A, et al. Terapia de fluidos en pacientes adultos crítica-
mente enfermos. Rev Col Anest 2005, 33: 25-49
30. Chamorro C, Romera MA, Márquez J. Farmacología de los coloides sintéticos Emer-
gencias 2004; 16: S28-S35
31. The SAFE Study Investigators. A comparison of albumin and saline for fluid resusci-
tation in the intensive care unit. N Engl J Med 2004; 350: 2247-56
32. The SAFE Study Investigators Saline or Albumin for Fluid Resuscitation in Patients
with Traumatic Brain Injury. N Engl J Med 2007; 357: 874-84
33. Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid reactions to colloid plas-
ma substitutes: frequency, risk factors, mechanisms. Ann Fr Anesth Reanim 1994;
13: 301-10
34. Jamnicki M, Bombeli T, Seifert B, et al. Low- and medium molecular- weight hy-
droxyethyl starches: comparison of their effect on blood coagulation. Anesthesiol-
ogy 2000; 93: 1231-7
35. Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis. An-
esthesiology 2005; 103: 654-60
36. Boldt J. Fluid choice for resuscitation of the trauma patient: a review of the phys-
iological, pharmacological, and clinical evidence. Can J Anesth 2004, 51: 500-13
37. Rudehill A, Gordon E, Ohman G, et al. Pharmacokinetics and effects of mannitol on
hemodynamics, blood and cerebrospinal fluid electrolytes, and osmolality during
intracranial surgery. J Neurosurg Anesthesiol 1993; 5: 4-12
38. Kobayashi T, Ichikawa T, Kondo R, et al. Pharmacokinetic study of mannitol in sub-
jects with increased ICP - Acta Neurochir Suppl (Wien) 1994; 60: 538-40
39. Muizelaar JP, Lutz HA 3rd, Becker DP. Effect of mannitol on ICP and CBF and corre-
lation with pressure autoregulation in severely head injured patients. J Neurosurg
1984; 61: 700 -6
40. Mendelow AD, Teasdale GM, Russell T, et al. Effect of mannitol on cerebral blood flow
and cerebral perfusión pressure in human head injury. J Neurosurg 1985; 63: 43-8
41. Myburgh JA, Lewis SB. Mannitol for Resuscitation in Acute Head Injury: Effects on
Cerebral Perfusion and Osmolality. Crit Care Resusc 2000; 2: 14-8
42. Burke A, Quest DO, Chien S, et al. The effects of mannitol on blood viscosity. Neu-
rosurg 1981; 55: 550- 53
43. The Brain Trauma Foundation. The American Association of Neurological Surgeons.
The Joint Section on Neurotrauma and Critical Care. Resuscitation of blood pres-
sure and oxygenation. J Neurotrauma 2000; 17: 471-8
314
Fluid Therapy in Acute Brain Injury

44. Chestnut RM. Management of brain and spine injuries. Critical Care Clinics 2004;
20: 25-55
45. Cooper DJ, Myles PS, Mc Dermott FT, et al. Prehospital hypertonic saline resuscita-
tion of patients with hypotension and severe traumatic brain injury: a randomized
controlled trial. JAMA 2004; 291: 1350-7
46. Baker AJ, Park E, Hare GMT, et al. Effects of resuscitation fluid on neurologic physi-
ology after cerebral trauma and hemorrhage. J Trauma 2008; 64: 348-57
47. Rovlias A, Kotson S. The influence of hyperglycemia on neurological outcome in pa-
tients with severe head injury. Neurosurgery 2000; 46: 335-43
48. Lam AM, Winn HR, Cullen BF, et al. Hyperglycemia and neurological outcome in pa-
tients with head injury. J Neurosurg 1991; 75: 545-51
49. Chambers IR, Treadwell L, Mendelow AD. Determination of threshold levels of ce-
rebral perfusion pressure and intracranial pressure in severe head injury by using
receiver-operating characteristic curves: an observational study in 291 patients. J
Neurosurg 2001; 94: 412-6
50. Juul N, Morris GF, Marshall SB, et al. Intracranial hypertension and cerebral per-
fusion pressure: influence on neurological deterioration and outcome in severe
head injury. The Executive Committee of the International Selfotel Trial. J Neuro-
surg 2000; 92: 1-6
51. Balestreri M, Czosnyka M, Hutchinson P, et al. Impact of intracranial pressure and
cerebral perfusion pressure on severe disability and mortality after head injury.
Neurocrit Care 2006; 4: 8-13
52. The Brain Trauma Foundation, American Association of Neurological Surgeons,
Joint Section on Neurotrauma and Critical Care. Cerebral Perfusion Thresholds. J
Neurotrauma 2007; 24(Supp 1): S59-S65
53. Tummala R, Sheth RN, Heros RC. Hemodilution and fluid management in neurosur-
gery. Clinical Neurosurgery 2006; 53: 238-251
54. Komotar R, Schmidt J, Starke RM, et al. Resuscitation and critical care of poor-
grade subarachnoid hemorrhage. Neurosurgery 2009; 64: 397-411
55. Hoff RG, vDijk GW, Algra A, et al. Fluid balance and blood volume measurement af-
ter aneurysmal subarachnoid hemorrhage. Neurocrit Care 2008; 8: 391-7
56. Hoff R, Rinkel G, Verweij B. Blood volume measurement to guide fluid therapy af-
ter aneurysmal subarachnoid hemorrhage. A prospective controlled study. Stroke
2009; 40: 2575-7
57. Horn P, Munch E, Vajkoczy P, et al. Hypertonic saline solution for control of elevat-
ed intracranial pressure in patients with exhausted response to mannitol and bar-
biturates. Neurol Res 1999; 21: 758-64
58. Qureshi AI, Suarez JI, Bhardwaj A, et al. Use of hypertonic (3%) saline/acetate infu-
sion in the treatment of cerebral edema: Effect on intracranial pressure and lateral
displacement of the brain. Crit Care Med 1998; 26: 440-6
59. Suarez JI, Qureshi AI, Bhardwaj A, et al. Treatment of refractory intracranial hyper-
tension with 23.4% saline. Crit Care Med 1998; 26: 1118-22
60. Suarez JI. Hypertonic saline for cerebral edema and elevated intracranial pressure.
Cleve Clin J Med 2004; 71 (Suppl 1): S9-S13
61. Rabinstein AA, Wijdicks EF. Hyponatremia in critically ill neurological patients. Neu-
rologist 2003; 9: 290-300
315
 Intensive Care in Neurology and Neurosurgery

62. Harrigan MR. Cerebral salt wasting syndrome: a review. Neurosurgery 1996; 38:
152-60
63. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med 2000; 342: 1581-9
64. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-
hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557-63
65. The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia
to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:
549-56
66. Tisherman SA. Hypothermia and injury. Current Opinion in Critical Care 2004; 10:
512-9

316