Hypertonic Saline Bolus Research Articles

An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia

The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). Laboratory experiment. University laboratory. Male Wistar rats weighing 240-330 g. Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 +/- 0.7 vs. 85 +/- 1.4, mean +/- se), and almost blunted neuronal cell death (hippocampal CA1, 2150 +/- 191 vs. 884 +/- 141 neurons/mm; cortex, 1746 +/- 91 vs. 1060 +/- 112). In contrast, delayed treatment resulted in no sustained effects. Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

A Single Bolus of 3% Hypertonic Saline with 6% Dextran Provides Optimal Initial Resuscitation After Uncontrolled Hemorrhagic Shock

The optimal fluid for early resuscitation of hemorrhagic shock would restore perfusion without increasing blood loss, hypothermia, acidosis, or coagulopathy. This study examined effects of a single bolus of hypertonic saline (HTS) with or without (+/-) dextran (D) after uncontrolled hemorrhage (UH) and determined optimal fluid composition. Fifty swine were anesthetized and underwent invasive line placement, celiotomy, splenectomy, suprapubic catheterization, and grade V liver injury. After 30 minutes of UH, blinded fluid resuscitation was initiated with a 250-mL bolus. Animals were randomized to five groups: normal saline (NS), 3% HTS (3%), 3% HTS/6% D (3% D), 7.5% HTS (7.5%), or 7.5% HTS/6% D (7.5% D). Mean arterial pressure (MAP) and tissue oxygen saturation (StO2) were recorded. Laboratory and thrombelastography (TEG) data were collected every 30 minutes. Animals were sacrificed 120 minutes after injury. Analysis of variance was used to compare groups. Significance was defined as p < 0.05. Baseline characteristics and laboratory values were similar in all groups. All groups achieved a similar degree of shock. Two NS and two 3% animals did not survive to 120 minutes. Fluids containing dextran produced a significantly greater increase in MAP (p < 0.02). Animals receiving 3% D maintained a higher MAP 90 minutes after fluid bolus. Also, 7.5% +/- D produced a significantly greater initial increase in StO2 (p < 0.05). This effect declined after fluid bolus while 3% D continued to improve tissue oxygenation. Significant differences developed between groups in TEG values, hematocrit, fibrinogen, urine sodium, serum sodium, serum chloride, and urine output. A single bolus of 3% D after uncontrolled hemorrhagic shock produces an adequate and sustained rise in MAP and StO2 and attenuates hypercoagulability. Resuscitation with 7.5% +/- D produces significantly increased urine output accompanied by a decline in MAP and StO2 over time. A single bolus of 7.5% D results in significant dilutional anemia and relative hypofibrinogenemia.

Protective effect of dexamethasone on osmotic-induced demyelination in rats

Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood–brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats ( P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.

Hypertonic saline enhances host response to bacterial challenge by augmenting receptor-independent neutrophil intracellular superoxide formation.

This study sought to determine whether hypertonic saline (HTS) infusion modulates the host response to bacterial challenge. Sepsis was induced in 30 Balb-C mice by intraperitoneal injection of Escherichia coli (5 x 107 organisms per animal). In 10 mice, resuscitation was performed at 0 and 24 hours with a 4 mL/kg bolus of HTS (7.5% NaCl), 10 animals received 4 mL/kg of normal saline (0.9% NaCl), and the remaining animals received 30 mL/kg of normal saline. Samples of blood, spleen, and lung were cultured at 8 and 36 hours. Polymorphonucleocytes were incubated in isotonic or hypertonic medium before culture with E. coli. Phagocytosis was assessed by flow cytometry, whereas intracellular bacterial killing was measured after inhibition of phagocytosis with cytochalasin B. Intracellular formation of free radicals was assessed by the molecular probe CM-H(2)DCFDA. Mitogen-activated protein (MAP) kinase p38 and ERK-1 phosphorylation, and nuclear factor kappa B (NFkappaB) activation were determined. Data are represented as means (SEM), and an analysis of variance test was performed to gauge statistical significance. Significantly reduced bacterial culture was observed in the animals resuscitated with HTS when compared with their NS counterparts, in blood (51.8 +/- 4.3 vs. 82.0 +/- 3.3 and 78.4 +/- 4.8, P = 0.005), lung (40.0 +/- 4.1 vs. 93.2 +/- 2.1 and 80.9 +/- 4.7, P = 0.002), and spleen (56.4 +/- 3.8 vs. 85.4 +/- 4.2 and 90.1 +/- 5.9, P = 0.05). Intracellular killing of bacteria increased markedly (P = 0.026) and superoxide generation was enhanced upon exposure to HTS (775.78 +/- 23.6 vs. 696.57 +/- 42.2, P = 0.017) despite inhibition of MAP kinase and NFkappaB activation. HTS significantly enhances intracellular killing of bacteria while attenuating receptor-mediated activation of proinflammatory cascades.

Antero-posterior activity changes in the superficial masseter muscle after exposure to experimental pain.

The aim of this randomized, controlled, double-blind study was to examine how the activation pattern of the masseter muscle changes during natural function when experimental pain is induced in a discrete anterior area of the muscle. In 20 subjects, three bipolar surface electrodes and three intramuscular fine-wire electrodes (antero-posterior mapping) were simultaneously attached above and in the right masseter muscle to record the electromyographic (EMG) activity during unilateral chewing before and after infusion of a 0.9% isotonic and 5% hypertonic saline bolus in the anterior area of the muscle. The activity of the contralateral masseter muscle was registered by surface electrodes. In addition, the development of pain intensity was quantitatively measured with a numerical rating scale (NRS). While both saline concentrations caused pain, the hypertonic solution evoked stronger pain. The experiments also provided evidence of a significant although differential activity reduction of the ipsilateral masseter muscle in the antero-posterior direction. The activity reduction decreased with increasing distance from the location of the infusion. The results support the idea that the strategy of differential activation protects the injured muscle while simultaneously maintaining optimal function.

Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension.

To review the literature on the use of hypertonic saline (HS) in treating cerebral edema and intracranial hypertension. Review of scientific and clinical literature retrieved from a computerized MEDLINE search from January 1965 through November 1999. Pertinent literature is referenced, including clinical and laboratory investigations, to demonstrate principles and efficacy of treatment with HS in patients with intracranial space-occupying pathology. The literature was reviewed to summarize the mechanisms of action, efficacy, adverse effects, systemic effects, and comparisons with standard treatments in both clinical and laboratory settings. HS has an osmotic effect on the brain because of its high tonicity and ability to effectively remain outside the bloodbrain barrier. Numerous animal studies have suggested that fluid resuscitation with HS bolus after hemorrhagic shock prevents the intracranial pressure (ICP) increase that follows resuscitation with standard fluids. There may be a minimal benefit in restoring cerebral blood flow, which is thought to be mitigated through local effects of HS on cerebral microvasculature. In animal models with cerebral injury, the maximum benefit is observed in animals with focal injury associated with vasogenic edema (cryogenic injury). The ICP reduction is seen for < or =2 hrs and may be maintained for longer periods by using a continuous infusion of HS. The ICP reduction is thought to be caused by a reduction in water content in areas of the brain with intact blood-brain barrier such as the nonlesioned hemisphere and cerebellum. Most comparisons with mannitol suggest almost equal efficacy in reducing ICP, but there is a suggestion that mannitol may have a longer duration of action. Human studies published to date reporting on the use of HS in treating cerebral edema and elevated ICP include case reports, case series, and small controlled trials. Results from studies directly comparing HS with standard treatment in regard to safety and efficacy are inconclusive. However, the low frequency of side effects and a definite reduction of ICP observed with use of HS in these studies are very promising. Systemic effects include transient volume expansion, natriuresis, hemodilution, immunomodulation, and improved pulmonary gas exchange. Adverse effects include electrolyte abnormalities, cardiac failure, bleeding diathesis, and phlebitis. Although unproven, a potential for central pontine myelinolysis and rebound intracranial hypertension exists with uncontrolled administration. HS demonstrates a favorable effect on both systemic hemodynamics and intracranial pressure in both laboratory and clinical settings. Preliminary evidence supports the need for controlled clinical trials evaluating its use as resuscitative fluid in brain-injured patients with hemorrhagic shock, as therapy for intracranial hypertension resistant to standard therapy, as firstline therapy for intracranial hypertension in certain intracranial pathologies, as small volume fluid resuscitation during spinal shock, and as maintenance intravenous fluid in neurocritical care units.

Estimation of parallel conductance by dual-frequency conductance catheter in mice.

The conductance catheter method has substantially enhanced the characterization of in vivo cardiovascular function in mice. Absolute volume determination requires assessment of parallel conductance (V(p)) offset because of conductivity of structures external to the blood pool. Although such a determination is achievable by hypertonic saline bolus injection, this method poses potential risks to mice because of volume loading and/or contractility changes. We tested another method based on differences between blood and muscle conductances at various catheter excitation frequencies (20 vs. 2 kHz) in 33 open-chest mice. The ratio of mean frequency-dependent signal difference to V(p) derived by hypertonic saline injection was consistent [0.095 +/- 0.01 (SD), n = 11], and both methods were strongly correlated (r(2) = 0.97, P < 0.0001). This correlation persisted when the ratio was prospectively applied to a separate group of animals (n = 12), with a combined regression relation of V(p(DF)) = 1.1 * V(p(Sal)) - 2.5 [where V(p(DF)) is V(p) derived by the dual-frequency method and V(p(Sal)) is V(p) derived by hypertonic saline bolus injection], r(2) = 0.95, standard error of the estimate = 1.1 microl, and mean difference = 0.6 +/- 1.4 microl. Varying V(p(Sal)) in a given animal resulted in parallel changes in V(p(DF)) (multiple regression r(2) = 0.92, P < 0.00001). The dominant source of V(p) in mice was found to be the left ventricular wall itself, since surrounding the heart in the chest with physiological saline or markedly varying right ventricular volumes had a minimal effect on the left ventricular volume signal. On the basis of V(p) and flow probe-derived cardiac output, end-diastolic volume and ejection fraction in normal mice were 28 +/- 3 microl and 81 +/- 6%, respectively, at a heart rate of 622 +/- 28 min(-1). Thus the dual-frequency method and independent flow signal can be used to provide absolute volumes in mice.

Direct Determination of Blood Recirculation Rate in Hemodialysis by a Conductivity Method

Blood recirculation is one of the key factors of decreasing dialysis efficiency. Determination of recirculation rate (R) is necessary to optimize effective dialysis delivery and to monitor vascular access function. R can be directly measured by a conductivity method in paired filtration dialysis (PFD), a double-compartment hemodiafiltration system that permits direct access to plasma water via the ultrafiltration stream. Measurement of R, in this system, involves the first of two conductivity sensors integrated in a urea monitor (UMS, BelIco-Sorin, Mirandola, Italy), and two saline injections. The rise in conductivity (deltaC1) induced by a 2.7 ml bolus of hypertonic saline 20% (mg/dl) in the arterial line serves for calibration, and is followed by an equivalent injection into the venous line, giving rise to deltaC2. The ratio deltaC2/deltaC1 equals R. A comparison between R values obtained with this method and with the low-flow technique in 31 chronic dialysis patients during 138 PFD sessions is reported. Mean R+/-SD by the conductivity method was 5.1+/-2.0 and 5.7+/-2.0% after 65 and 155 minutes of PFD (correlation coefficient, r = 0.75), whereas it was 6.4+/-4.9% and 5.5+/-4.6% after 30 sec of low blood pump flow for urea and creatinine markers, respectively (r = 0.35). After 120 sec of low flow, mean R increased to 9.0+/-5.1 and 8.8+/-4.6% for urea and creatinine, respectively (r = 0.45). Considerable discrepancies were found in R values measured simultaneously with the two blood markers. Statistically significant differences were found between the two measurement modalities (blood-side and conductivity); the correlation coefficients (r) varied between 0.28 and 0.41. The observed differences in mean R results do not seem considerable from a clinical perspective. The best agreement between blood-side and conductivity R measurements was obtained with Rcreat after 30 sec of low flow. Overall, a wider distribution was found in R values from blood-side determinations, most likely consequent to variability in the dosing method. The conductivity method appears more accurate and simple in assessing total R, and can be readily automated and integrated into the dialysis machine. The authors, therefore, recommend evaluation of R using methods not based on chemical blood concentration values.

Alkalinization is ineffective for severe hyperkalemia in nonnephrectomized dogs. Hyperkalemia Research Group.

To determine whether alkalinization with sodium bicarbonate (NaHCO3) in near-lethal hyperkalemia either lowers potassium (K) rapidly or shortens duration of cardiac conduction disturbances. A controlled canine laboratory investigation of 3 treatments for severe hyperkalemia. Conditioned dogs (n = 8; 17-30 kg) received, in random order, 2 mmol/kg of each of 3 treatments (matched in sodium and water) in separate experiments > or = 1 week apart: 1.05% NaHCO3 over 60 minutes (infusion therapy); 8.4% NaHCO3 over 5 minutes, then 14 mL/kg sterile water over 55 minutes (bolus therapy); 8.4% NaCl over 5 minutes, then 14 mL/kg sterile water over 55 minutes (saline therapy). Prior to administering one of the above therapies, the animals were anesthetized with 0.5-2.5% isoflurane and ventilated to maintain a normal PCO2. After 30 minutes of equilibration, 2 mmol/kg/hr (loading dose) of a 2-mmol/mL KCl solution was given until idioventricular or relative junctional bradycardic dysrhythmias were sustained for 15 minutes. Then KCl was decreased to 1 mmol/kg/hr (maintenance dose) for 2 hours and 45 minutes. Treatment was begun after 45 minutes of maintenance KCl infusion. The pretreatment K level (all studies) was 9.06 +/- 0.82 mmol/L (mean +/- SD). Although the mean K level decreased more after saline therapy than after bolus therapy at every time, differences were neither statistically significant nor clinically important during the first 30 minutes. The means of the differences in decreases (saline minus bolus) were small, 0.26 (95% CI, -0.48 to 1.00) at 15 minutes, 0.16 (95% CI, -0.67 to 0.98) at 30 minutes. Dysrhythmia duration was shorter with bolus therapy than for saline therapy in only 1 of 5 dogs (p = 0.38). Hypertonic saline bolus lowered plasma K as effectively as NaHCO3 bolus in this animal model within the first 30 minutes. Clinically meaningful decreases due to alkalinization alone within 30 minutes are unlikely.

Short term volume effects of a hypertonic saline bolus during neurosurgery

Intracranial hypertension which does not respond to customary hyperosmotic agents may successfully be treated with hypertonic saline. The absence of diuresis and the maintainance of intravascular volume are supposed to be the main advantages of hypertonic sodium chloride. Volume overload and toxic hyperosmolality from frequent application of such solutions are possible disadvantages. The presented experiments checked the time course of intravascular volume shifts after a 100 ml 1-molar saline bolus in 14 patients during neurosurgery using plasma protein concentration changes. An initial intravascular volume expansion of about 270 ml remained quite unchanged for the first 8 minutes, followed by a nearly linear decrease. Extrapolation of the curves demonstrated that the preinfusion state would have been reached after about 20 minutes. Osmolality remained increased by about 4 mosmol/kg 15 min after the bolus. Thus it appears that repetitive infusion of these amounts of hypertonic saline will cause no serious volume overload if 30 minutes intervals are kept, but osmolality should be checked before each bolus.

Continuous measurement of left ventricular volume in animals and humans by conductance catheter.

An eight-electrode conductance catheter previously developed by us and used to determine stroke volume in dogs was applied in human beings and dogs to measure absolute left ventricular volume quantitatively. For calibration we developed the formula V(t) = (1/alpha)(L2/sigma b)G(t) - Vc, where V(t) is time-varying left ventricular volume, alpha is a dimensionless constant, L is the electrode separation, sigma b is the conductivity of blood obtained by a sampling cuvette, and G(t) is the measured conductance within the left ventricular cavity. Vc is a correction term caused by the parallel conductance of structures surrounding the cavity and is measured in two ways. The first method, applicable in the anesthetized animal, consists of temporary reduction of volume to zero by suction. The second method uses a transient change in sigma b by injection of a small bolus of hypertonic saline (dogs) or 10 ml of cold glucose (humans) into the pulmonary artery. The validity of the formula was previously established for the isolated postmortem canine heart. The predicted linearity, slope constant alpha, and accuracy of Vc for the left ventricle in vivo were investigated by comparing the conductance volume data with results from independent methods: electromagnetic blood flow measurement for stroke volume and indicator dilution technique for ejection fraction (dogs), thermal dilution for cardiac output (12 patients), and single-plane cineventriculography for V(t) (five patients). In all comparisons, linear regression showed high correlation (from r = .82 [n = 46] to r = .988 [n = 20]) while alpha, with one exception, ranged from 0.75 to 1.07 and the error in Vc ranged from 0.5% to 16.5% (mean 7%). After positioning of the catheter, no arrhythmias were observed. It is concluded that the conductance catheter provides a reliable and simple method to measure left ventricular volume, giving an on-line, time-varying signal that is easily calibrated. Together with left ventricular pressure obtained through the catheter lumen, the instrument may be used for instantaneous display of pressure-volume loops to facilitate assessment of left ventricular pump performance.