|Hypertonic solution for pediatric patients
Soluções hipertônicas em pediatria
|Werther Brunow de Carvalho|
J Pediatr (Rio J) 2003;79 Suppl 2:S187-S94
Objective: To describe the current knowledge and indications for use of hypertonic saline solutions in pediatrics patients.
Sources of data: Medline recent review articles and personal files.
Summary of the findings: Basic physiologic principles were reviewed concerning the distribution of fluid inside the intravascular, interstitial and intracellular compartments. We also reviewed the findings concerning the mechanisms responsible for the rapid onset of cardiocirculatory effects and the additional effect of the colloid component. Finally, we present the medical terms used in the context of small-volume resuscitation, the indications for clinical use, the evidence from clinical research (hemorrhagic shock, preclinical trauma care, septic shock, and head trauma), and the disadvantages and potential adverse effects of small-volume resuscitation.
Conclusions: Resuscitation by means of hypertonic saline solutions associated or not with colloid solutions is one of the most innovative concepts for primary resuscitation from trauma and shock established in the past decade. Currently, the spectrum of potential indications involves not only prehospital trauma care, but also perioperative and intensive care therapy. However, additional randomized double-blind studies are required with both children and adult patients to confirm the advantages of the method in terms of survival.
Figure 1 -Plasma osmolar concentration, interstitial and intracellular fluid. Note that the main cation in the plasma and in the interstitial fluid is sodium, while in the intracellular fluid the main cation is potassium. Adaptad from West JBE ( ), 1985.
Although intracellular and interstitial osmolality are identical, plasma
osmolality is slightly higher resulting in important clinical implications
for the choice of resuscitation fluid. Plasma has a much higher protein
concentration than the interstitial space and these molecules do not pass
trough vascular endothelium.
A term that is used to describe a solution is its tonicity which refers
to its osmolality relative to plasma. A solution is said to be isotonic
when the normal cells of the organism can be suspended in this environment
with no alteration in volume. This implies that the solution has the same
osmolality as plasma, and they are therefore isoosmolar. Habitually used
solutions, such as saline at 0.9% and Ringer lactate are isotonic. The
sodium in these solutions will primarily remain within the extracellular
space. Therefore, an infusion of saline at 0.9% can result in expansion
of the total extracellular space distributed so that 1/3 of the volume
is in the intravascular space and 2/3 is in the interstitial space, resulting
in no increase to extracellular osmolality nor intracellular volume.
Figure 2 -Body fluids, causes of hypovolemia and the impact of the infusion of hypertonic saline solution in the mobilization of the intravascular compartment. Adaptad from Guyton AC, 1991 ( ).
Additionally during shock and ischemia, there is an increase in endothelial
cell volume due to lost adenosine triphosphate (ATP) and cell membrane
exchange dysfunction, resulting in water accumulation in the cells. Therefore,
any mobilization of water from the intracellular compartment, would have
two important advantages: 1) a rapid increase in plasma volume, of 3 to
4 times the infused volume; 2) normalization of endothelial cell volume
and luminal diameter recovering small vessels, with increased blood flow
in microcirculation as a result (Figure 3).
Figure 3 -Microcirculatory effects of hyperosmotic/hyperoncotic solutions.
The term small-volume resuscitation was used by Nakayama et al., 1984 (), in reporting on an experimental model of hemorrhagic shock using sheep, in which there was recovery of cardiac output and a significant increase in systemic pressure immediately after infusion of a hypertonic saline solution (NaCl 7.5% = 2,400 mosm/l). Following this, a number of different clinical and experimental studies were carried out to investigate hypertonic solutions (NaCl, glucose, mannitol, sodium bicarbonate, sodium acetate, saline with lactate, urea, Tris-Cl), with variable doses, (4-6 ml/kg), differing concentrations of sodium chloride (1.5-30% NaCl), speed of infusion (2-15 minutes) and different administration routes (intravenous, intraosseous). This research also evaluated efficacy in respect of restoration of macro and microcirculatory parameters, organ dysfunction and survival rates.
Researchers were concerned about the resuscitation response soon after small-volume resuscitation, when a hypertonic saline solution is used in isolation, therefore the saline solution (7.2-7.5%) was combined with a colloid solution which has an elevated capacity to bond with water (dextran 60/70 4.2-24% or hydroxyethyl starch 60-20%), in order to preserve intravascular volume, thus obtaining a synergic effect from the increase in plasma osmolality with resultant mobilization of intracellular water and increase in plasma oncotic pressure in an attempt to conserve the volume effect (). Consequentially, the meaning of small-volume resuscitation or hypertonic small-volume resuscitation changed, currently indicating primary resuscitation from hypovolemia and shock by means of a hypertonic saline-colloid solution (Table 1).
Table 1 -
Based on experimental data obtained in cases of traumatic and hemorrhagic
shock, it is possible to sum up the effects of primary resuscitation with
hypertonic saline solution in isolation or in combination with hyperoncotic
solutions as being (
- Immediate increase in systemic pressure and cardiac output with reduced
peripheral vascular resistance.
Current data from controlled clinical trials has shown that the use of small-volume resuscitation is practicable and effective compared with conventional fluid therapy for primary resuscitation of patients with trauma (A list of potential indications for small volume resuscitation in emergency care, during the perioperative period and in critically ill patients can be found in Table 2. ), and also in the emergency room ( ). Research into the pre-hospital stage of resuscitation have demonstrated favorable results in cases of severe trauma requiring immediate surgery ( ). Data from a multicenter study ( ) suggest that patients with trauma and hypotension, presenting a Glasgow coma score less than or equal to 8 may benefit from resuscitation with an NaCl solution at 7.5%. A revision performed by the Cochrane Library, however, revealed that there is a problem in terms of a lack of data proving the efficacy of hypertonic crystalloids in reducing mortality among patients with hypovolemia with or without head traumas ( ).
Table 2 -
There are a number of different solutions available which contain hypertonic saline associated with a colloid agent (Table 3).
Table 3 -
Some of the combined solutions (hypertonic NaCl/colloid) are not available in our region, but in physiological terms the colloid adds specific beneficial effects, multiplying the effect of the hypertonic saline solution. However, the addition of a colloid compound can lead to an increased incidence of side effects, such as anaphylactic reaction.
Researching thermal lesions, Horton et al. (), employing an experimental model using burnt pigs (45% of body surface area burnt), employed intravenous infusion with small volumes of saline at 7.5%/6% dextran-70 as a supplement to standard resuscitation with Ringer lactate. This strategy improved heart contraction performance, reduced cardiac myocyte damage and reduced total volume of fluids during the first 24 hours post burn. In 1973, Monafo et al. ( ), described the resuscitation of 25 children and 81 adults with a burnt area greater than 20%, using hypertonic saline solution at a number of different concentrations continuously. The data indicated that resuscitation volumes were 20 to 25% lower than those calculated by the Parkland formula. In 1983, Bowser et al. ( ), evaluated 39 children with large areas of burns resuscitated with hypertonic solution (17 patients), hypotonic solution (11 patients) or colloid (11 patients). Resuscitation with hypertonic solution resulted in lower sodium and water losses via the burn; produced a more significant increase in urinary volume than Ringer lactate infusion during the first 24 hours post burn; resulted in less weight gain; and had a better cost-effectiveness ratio than resuscitation with colloid solution. There were no statistically significant differences between the group on hypertonic solution and colloid solution, in respect of morbidity and mortality. These investigations concluded that hypertonic solutions are simple, safe and effective for acute burn management. More recently, Murph et al. ( ) evaluated the systemic and resuscitation effects and also the safety of infusions of NaCl 7.5%/6% dextran-70 solution, given as a support during standard resuscitation with Ringer lactate after severe thermal damage, concluded that there were no adverse side effects related to hemodynamic or metabolic condition after infusion of the combined solution. Early administration of the combined solution after severe thermal lesion can reduce cardiac dysfunction related to burning.
The use of hyperosmotic solutions during heart surgery was first carried
out by Boldt et al. (
In 1997, Wade et al. () performed a meta-analysis of research in which hypertonic saline solution/dextran or hypertonic saline solution in isolation had been used as the primary fluid therapy for patients with traumatic lesions. The analysis included eight studies evaluating a total of 1,170 patients. The inclusion criterion for trauma patients was systolic arterial pressure below 100 mmHg. There were no significant differences in 30-day survival rates when hypertonic saline solution (7.5%) was compared with Ringer lactate, however, there was a 5.1% increase in survival rates when hypertonic saline solution/dextran (NaCl 7.5%/6% dextran-70) was compared.
When the role of hypertonic solutions in septic shock was analyzed, animal research (), demonstrated a significant reduction in albumin leakage, in neutrophil counts from broncho-alveolar lavage and in the degree of histopathological damage when compared with resuscitation with Ringer lactate. There are few studies of humans which have evaluated hypertonic solution in patients with sepsis. One of these demonstrates improvements in resuscitation parameters among clinically stable sepsis patients ( ). Twenty-none patients were included in the study and received either 250 ml saline or hypertonic solution (NaCl 7.5%/8% dextran-70). Cardiac index and systolic volume were greater in the group that received hypertonic solution, with differences being most apparent 1 hour after infusion.
Currently there is interest in the use of hypertonic solutions as osmotic
substances which increase intravascular volume and combat increased intracranial
Figure 4 -
Another prospective study, by Kanna et al. (), evaluated the effect of prolonged infusion of NaCl solution at 3% with 10 pediatric patients with traumatic brain damage and refractory hypertension intracranial despite conventional treatments.
Hypertonic solution of NaCl works by increasing sodium and serum osmolality, creating an osmotic gradient which transfers water from the intracellular compartment of the brain to the interstitial, thus reducing cerebral edema and intracranial pressure. While mannitol has a similar action, sodium chloride has a more favorable reflection coefficient (1.0) than does mannitol (0.9), making hypertonic solutions ideal agents when these effects are desired. Hypertonic solution can also normalize the resting membrane potential and cell volume, restoring the intracellular electrolyte balance of damaged cells, suggesting that this treatment could have preferential benefits in damaged areas of the brain ().
The infusion in bolus of a hypertonic NaCl solution to a peripheral vein at a concentration above 10% causes significant hemolysis while solutions at 7-7.5% are reported to be safe. Although the concept of resuscitation with hypertonic solutions involves a considerable increase in osmolar charge, work carried out to date does not report any acute clinical signs of hyperosmolality. Serum osmolality reduces after the first 4-8 hours of infusion and, after 24 hours there is no difference between patients who have received hypertonic saline solution and controls ().
There may also be electrolyte disturbances, primarily related to the sodium. Neuropathological signs of continuous central myelinolysis were not found in any of the patients that died. Chlorine levels also increase and may be associated with acidosis (hyperchloremic acidosis).
The addition of a crystalloid solution is also not immune to risks,
primarily anaphylactic reactions. However, none of the controlled clinical
trials attributed adverse effects to the colloid component (
Table 4 -
Other effects of hypertonic solutions
Some physiological alterations associated with hypertonic fluids include
alterations to the cytotoxicity of leukocytes (
|Werther Brunow de Carvalho - Department of Pediatrics, School of Medicine, Universidade Federal de São Paulo. PICU, Hospital São Paulo, Hospital Santa Catarina and Beneficiência Portuguesa de São Paulo, São Paulo, SP, Brazil.|
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