Dan Drobin

Volume Kinetics of Ringer's Solution in Hypovolemic Volunteers

BACKGROUND The amount of Ringers solution needed to restore normal blood volumes is thought to be three to five times the volume of blood lost. This therapy can be optimized by using a kinetic model that takes accounts for the rates of distribution and elimination of the infused fluid. METHODS The authors infused 25 ml/kg Ringers acetate solution into 10 male volunteers who were 23 to 33 yr old (mean, 28 yr) when they were normovolemic and after 450 ml and 900 ml blood had been withdrawn. One-volume and two-volume kinetic models were fitted to the dilution of the total venous hemoglobin and plasma albumin concentrations. RESULTS Withdrawal of blood resulted in a progressive upward shift of the dilution-time curves of both markers. The two-volume model was statistically justified in 56 of the 60 analyzed data sets. The hemoglobin changes indicated that the body fluid space expanded by the infused fluid had a mean total volume of 10.7 l(+/-0.9 SEM). The elimination rate constant (kr) decreased with the degree of hypovolemia and was 133 ml/min (22 ml/min [SEM]), 100 ml/min (39 ml/min [SEM]), and 34 ml/min (7 ml/min [SEM]), respectively (P < 0.01). Plasma albumin indicated a slightly larger body fluid space expanded by the infused fluid, but kr was less (P < 0.02). Hypovolemia reduced the systolic and diastolic blood pressures by approximately 10 mmHg (P < 0.05). CONCLUSIONS The dilution of the blood and the retention of infused Ringers solution in the body increases in the presence of hypovolemia, which can be attributed chiefly to a reduction of the elimination rate constant.

Kinetics of isotonic and hypertonic plasma volume expanders.

Background Major differences in plasma volume expansion between infusion fluids are fairly well known, but there is a lack of methods that express their dynamic properties. Therefore, a closer description enabled by kinetic modeling is presented. Methods Ten healthy male volunteers received, on different occasions, a constant-rate intravenous infusion over 30 min consisting of 25 ml/kg of 0.9% saline, lactated Ringers solution, acetated Ringers solution, 5 ml/kg of 7.5% saline, or 3 ml/kg of 7.5% saline in 6% dextran. One-, two-, and three-volume kinetic models were fitted to the dilution of the total venous hemoglobin concentration over 240 min. Osmotic fluid shifts were considered when hypertonic fluid was infused. Results All fluids induced plasma dilution, which decreased exponentially after the infusions. The ratio of the area under the dilution-time curve and the infused fluid volume showed the following average plasma-dilution dose-effect (efficiency), using 0.9% saline as the reference (= 1): lactated Ringers solution, 0.88; acetated Ringers solution, 0.91; hypertonic saline, 3.97; and hypertonic saline in dextran, 7.22 (“area approach”). Another comparison, based on kinetic analysis and simulation, showed that the strength of the respective fluids to dilute the plasma by 20% within 30 min was 0.94, 0.97, 4.44, and 6.15 (“target dilution approach”). Between-subject variability was approximately half as high for the latter approach. Conclusions The relative efficiency of crystalloid infusion fluids differs depending on whether the entire dilution-time profile or only the maximum dilution is compared. Kinetic analysis and simulation is a useful tool for the study of such differences.

Lower dose of hypertonic saline dextran reduces the risk of lethal rebleeding in uncontrolled hemorrhage.

To challenge whether the recommended dose of 4 mL/kg of 7.5% sodium chloride in 6% Dextran (HSD) is optimal for fluid resuscitation in uncontrolled hemorrhage, 30 anesthetized pigs were randomized to receive a 5-min intravenous infusion of either 1, 2, or 4 mL/kg of HSD beginning 10 min after inducing a 5-mm laceration in the infrarenal aorta. In addition to conventional hemodynamic monitoring, the blood loss was calculated as the difference in blood flow rates between flow probes placed proximal and distal to the injury. The results show that the bleeding stopped between 3 and 4 min after the injury and amounted to 338 ± 92 mL (mean ± SEM), which corresponds to 28.5% ± 6.6% of the estimated blood volume. After treatment with HSD was started, six rebleeding events occurred in the 1-mL group, 11 in the 2-mL group, and 16 in the 4-mL group. The amount of blood lost due to rebleeding increased significantly with the dose of HSD and was also associated with a fatal outcome. The total blood loss was 408 mL in the survivors and 630 mL in the nonsurvivors (median, P < 0.007). The mortality in the three groups was 20%, 50%, and 50%, respectively. In conclusion, infusing 4 mL/kg of HSD after uncontrolled aortic hemorrhage promoted rebleeding and increased the mortality, while a dose of 1 mL/kg appeared to be more suitable.

Distribution and elimination of crystalloid fluid in pre-eclampsia.

Pre-eclampsia (PE) is a disease of pregnancy associated with peripheral oedema and hypovolaemia, but few details are known about how women with PE handle a volume load of crystalloid fluid compared with healthy pregnant women. To study this issue, Ringers acetate solution (12.5 ml/kg of body weight) was given by intravenous infusion over 30 min to eight women with PE and to eight healthy pregnant women matched with respect to gestational week (mean, 34 weeks). Venous blood was sampled and excreted urine was collected over 90 min to study the time course of the volume expansion by means of volume kinetic analysis. The results show that the size of the central body fluid space expanded by the infused fluid was smaller in PE (mean, 2940 ml compared with 4240 ml respectively; P<0.04), and the clearance constants for distribution (100 ml/min compared with 43 ml/min; P<0.04) and elimination (125 ml/min compared with 36 ml/min; P<0.02) were higher in the women with PE than in the controls. Less excess volume accumulated in the central body fluid space in the presence of PE, whereas the rates of distribution and elimination were higher during and for 15 min after the infusion. It is concluded that Ringers acetate solution fluid is both distributed and eliminated faster in women with PE than in matched pregnant controls.

Bilateral vagotomy inhibits apnea and attenuates other physiological responses after blunt chest trauma.

BACKGROUND Behind armor blunt trauma (BABT) is defined as the nonpenetrating injury resulting from a ballistic impact on body armor. Some of the kinetic energy is transferred to the body, causing internal injuries and, occasionally, death. The aim of this study was to investigate if apnea and other pathophysiological effects after BABT is a vagally mediated reflex. METHODS Sixteen anesthetized pigs wearing body armor, of which five were vagotomized, were shot with a standard 7.62 mm assault rifle. These animals were compared with control animals (n = 8), shot with blank ammunition. We performed bilateral vagotomy before the shot and assessed the outcome on the apnea period, respiration, circulation, and brain function. Animals were monitored during a 2-hour period after the shot. RESULTS Nonvagotomized animals had a mean apnea period of 22 (6-44) seconds. This group also showed a significant decrease in oxygen saturation compared with control animals. Furthermore, electroencephalogram-changes were more pronounced in nonvagotomized animals. In contrast, vagotomized animals were protected from apnea and showed only a minor decrease in oxygen saturation. All exposed animals showed impaired circulation, and postmortem examination revealed a pulmonary contusion. CONCLUSION This study shows that apnea after BABT is a vagally mediated reflex that can be inhibited by bilateral vagotomy. Our results indicate that the initial apnea period is an important factor for hypoxia after BABT. Supported ventilation should begin immediately if the affected person is unconscious and suffers from apnea. It should continue until the neurologic paralysis disappears and sufficient spontaneous breathing begins.

Effects of Fluid Resuscitation With Hypertonic Saline Dextrane or Ringerʼs Acetate After Nonhemorrhagic Shock Caused By Pulmonary Contusion

BACKGROUND Injured lungs are sensitive to fluid resuscitation after trauma. Such treatment can increase lung water content and lead to desaturation. Hypertonic saline with dextran (HSD) has hyperosmotic properties that promote plasma volume expansion, thus potentially reducing these side effects. The aim of this study was to (1) evaluate whether fluid treatment counteracts hypotension and improves survival after nonhemorrhagic shock caused by lung contusion and (2) analyze whether resuscitation with HSD is more efficient than treatment with Ringers acetate (RA) in terms of blood oxygenation, the amount of lung water, circulatory effects, and inflammatory response. METHODS Twenty-nine pigs, all wearing body armor, were shot with a 7.62-mm assault rifle to produce a standardized pulmonary contusion. These animals were allocated into three groups: HSD, RA, and an untreated shot control group. Exposed animals were compared with animals not treated with fluid and shot with blank ammunition. For 2 hours after the shot, the inflammatory response and physiologic parameters were monitored. RESULTS The impact induced pulmonary contusion, desaturation, hypotension, increased heart rate, and led to an inflammatory response. No change in blood pressure was observed after fluid treatment. HSD treatment resulted in significantly less lung water (p < 0.05) and tended to give better Pao2 (p = 0.09) than RA treatment. Tumor necrosis factor-α release and heart rate were significantly lower in animals given fluids. CONCLUSION Fluid treatment does not affect blood pressure or mortality in this model of nonhemorrhagic shock caused by lung contusion. However, our data indicate that HSD, when compared with RA, has advantages for the injured lung.

Leukocytosis after fluid loading and induction of epidural anesthesia

The present study shows that leukocytosis occurs from fluid loading and from the small amounts of adrenaline given epidurally. Five healthy volunteers received an intravenous infusion of 25 ml·kg−1 b.w. of Ringers acetate solution over 15, 30, 45, and 80 min, and epidural anesthesia (EDA) was induced in 25 urology patients using mepivacaine 2% with or without adrenaline 1∶200 000. In the volunteers, we found that the total leukocyte count increased by up to 33% within 1 h after rapid volume loading. This increase was accounted for by neutrophils and lymphocytes. In the patients, the leukocyte count increased by 32% during the onset of EDA when mepivacaine with adrenaline was used. This increase was accounted for by lymphocytes. Our results suggest that caution is needed when interpreting the importance of a raised leukocyte count in samples taken in association with fluid loading and also when EDA is induced by a local anesthestic solution that contains adrenaline.