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Background: Resuscitation with hypertonic saline/dextran (HSD) has been suggested to be efficacious in patients who have traumatic brain injury and are hypotensive. We undertook a cohort analysis of individual patient data from previous prospective randomized double-blinded trials to evaluate improvements in survival at 24 hours and discharge after initial treatment with HSD in patients who had traumatic brain injury (head region Abbreviated Injury Score > or = 4) and hypotension (systolic blood pressure < or = 90 mm Hg)., Methods: All variables and end points were defined before initiation of data handling. Investigators were blind as to the treatment. Case report forms were received from six studies. Of these, 223 patients met the inclusion for traumatic brain injury. Comparisons between HSD and standard of care were made using stratified analysis and logistic regression to assess efficacy, confounding, and interaction. Potential confounding variables of pre-fluid treatment, Glasgow Coma Scale score (3-8 vs. 9-15), injury type, and systolic blood pressure can be considered a priori factors that were known before randomization. Effects of the various trials was also considered., Results: Treatment with HSD resulted in a survival until discharge of 37.9% (39 of 103) compared with 26.9% (32 of 119) with standard of care (p = 0.080). Using logistic regression, adjusting for trial and potential confounding variables, the treatment effect can be summarized by the odds ratio of 2.12 (p = 0.048) for survival until discharge., Conclusions: Patients who have traumatic brain injuries in the presence of hypotension and receive HSD are about twice as likely to survive as those who receive standard of care.

Objective: To evaluate the use of 250 mL of a 7.5% sodium chloride solution, both with and without added dextran 70, for the prehospital resuscitation of hypotensive trauma patients., Design: Double-blind randomized trial., Setting: Six trauma systems served by helicopter transport., Patients: Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport., Interventions: Infusion of study solution, in the field or during transport, followed by conventional isotonic solutions as needed. Solutions studied in four cohorts were as follows: (1) lactated Ringer's; (2) 7.5% sodium chloride (hypertonic saline); (3) 7.5% sodium chloride combined with 6% dextran 70; and (4) 7.5% sodium chloride combined with 12% dextran 70., Main Outcome Measures: Blood pressure response; survival to time of hospital discharge among the treatment groups; and survival compared with that predicted by norms from the Major Trauma Outcome Study (MTOS)., Results: The mean (+/- SD) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer's solution group (34 +/- 46 vs 11 +/- 49 mm Hg, P < .03). Overall survival in the four treatment groups was 49%, 60%, 56%, and 45% (not statistically significant). Survival in the hypertonic saline solution group, however, was significantly higher than that predicted by the MTOS norms (60% vs 48%, P < .001). Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group (P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis; with survival in the hypertonic saline solution group [34%] vs lactated Ringer's solution group [12%])., Conclusions: Prehospital infusion of 250 mL of 7.5% sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms. Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5% sodium chloride resuscitation. Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70.

Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock, and seem to be effective in resuscitating trauma patients with severe injuries. In this study, the contribution of the dextran component was investigated in a prospective, three-armed, double-blind, randomized trial. Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of (1) normal saline (NS); (2) 7.5% NaCl (HS, for hypertonic saline); or (3) 7.5% NaCl in 6% dextran 70 (HSD). Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients' conditions indicated. By predetermined hypothesis, the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology. The 7.5% NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology. The addition of a colloid, in the form of 6% dextran 70, did not offer any additional benefit, at least in this setting of rapid urban transport.

To evaluate the use of hypertonic saline/dextran solutions in the prehospital resuscitation of severely injured patients, we administered 250 mL of either 7.5% sodium chloride/dextran 70 (HSD) (n = 83) or lactated Ringer's solution (n = 83), followed by conventional isotonic fluids, to 166 trauma patients with systolic blood pressures less than or equal to 100 mm Hg, in a prospective, randomized, double-blinded clinical trial. Patients in the sodium chloride/dextran 70 group required less fluid before hospitalization and arrived in the emergency department with higher systolic blood pressures than patients in the lactated Ringer's solution group. The rate of survival to hospital discharge for the entire cohort was 64% for patients in the sodium chloride/dextran 70 group vs 59% for patients in the lactated Ringer's solution group. The rate of survival to hospital discharge for the patients with severe head injuries was 32% for the sodium chloride/dextran 70 group vs 16% for the lactated Ringer's solution group. Actuarial survival for patients with severe head injuries in the sodium chloride/dextran 70 group compared with patients with severe head injuries in the lactated Ringer's solution group did not quite reach statistical significance. There were no adverse side effects associated with sodium chloride/dextran 70 administration. Administration of small volumes of sodium chloride/dextran 70 before hospitalization increased the blood pressure of severely injured patients more effectively than did lactated Ringer's solution and showed tendencies toward improving survival in the patients with severe head injuries.

In an effort to find the best hypertonic saline-dextran solution (HSD) for prehospital use, 33 chronically catheterized sheep were bled using a fixed pressure shock model (50 mm Hg x 2 hours) and resuscitated with 4 ml/kg of HSD solution (2-minute bolus). In the first set of experiments colloid was varied and sodium chloride was held constant, as 7.5% NaCl was paired with either 0%, 6%, or 12% dextran 70. A dose-response relationship existed, with cardiac output increasing 20% with each sequential dextran 70 concentration. Mean arterial blood pressure was higher in animals that were resuscitated with either the 7.5% NaCl/6% dextran 70 or 7.5% NaCl/12% dextran 70 solution (p less than 0.05). Using the optimal dextran 70 concentration from the first set of experiments (i.e., 12%), solute was varied in a second set of experiments comparing 0.9%, 3.8%, 7.5%, or 10% NaCl/12% dextran 70. Again, dose-response features were demonstrated, as cardiac output increased as a function of NaCl concentration. However, this response plateaued with the 7.5% NaCl concentration and no advantage was obtained by increasing the NaCl concentration to 10%. We conclude that a 4-ml/kg bolus of 7.5% NaCl/12% dextran 70 solution may be a more effective form of therapy than those previously evaluated. This new solution is now being included in our ongoing clinical trials.

Although it had been known for several years that central venous injections of hypertonic salt solutions with added dextran could effectively resuscitate animals from hemorrhagic shock, it was not known whether peripheral injections could result in the same beneficial effects. Chronically instrumented, unrestrained, and unanesthetized sheep were subjected to a moderate degree of hemorrhagic shock and then resuscitated with a 2-minute infusion of 7.5% NaCl/6% dextran 70 in a volume of 5 ml/kg body weight. Infusions were made into the cephalic vein, the femoral artery, or, centrally, the superior vena cava. All three routes of injection promptly reestablished arterial pressure and cardiac output. All gave equivalently good restoration of plasma volume. None of the injections damaged the vessels, as determined either by gross inspection or by histologic examination. Thus the solution was safe and effective when given peripherally. It might be useful in the field resuscitation of hypovolemic patients.

Animal studies and preliminary field patient trials suggest that hypertonic saline solutions can achieve resuscitation of hypovolemic shock with extremely small volumes. In the study reported here, we evaluated the effects of a hypertonic 7.5% NaCl/6% Dextran 70 (HSD) solution in the resuscitation of patients in the emergency room. Thirty-two patients were randomized into a prospective, randomized, placebo-controlled, double-blinded trial in which 250 ml of either HSD or, as a control, lactated Ringers (LR) was used as the initial fluid for resuscitation of patients with systolic blood pressures of 80 mmHg or less. The test solution was given intravenously, usually through a saphenous vein cut-down, over a period of 2-5 minutes. Conventional isotonic solutions were then given as necessary with an average of 2500 ml of fluid being given over the first 30 minutes of resuscitation. Survival was not improved, and the trial proved to be of most interest with regard to measurement of physiological quantities, which might have been expected to have been substantially abnormal because, in many cases, the measurements were made shortly after the infusion ran in. Very few abnormalities, however, were in fact detected. With the exception of one patient, the highest sodium concentration was 156 mEq/l, the highest chloride concentration was 126 mEq/1, and the highest osmolality was 401 mOsm/kg, and this value was obtained in a patient in the control LR group. Osmolality correlated far better with blood alcohol levels (Spearman's rank correlation coefficient = 0.81) than with any other variable, including sodium and chloride concentrations. The HSD solution was safe to use.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringer's solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field.

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.