G. C. Kramer

A comparison of several hypertonic solutions for resuscitation of bled sheep

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.

3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients.

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 Ringers 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.

Infusion of very hypertonic saline to bled rats: Membrane potentials and fluid shifts

Anesthetized rats were subjected to a moderate degree of hemorrhagic shock, lowering their mean arterial pressure to approximately 50 mm Hg for approximately 100 min. At the end of the shock period, resting skeletal muscle transmembrane potentials had depolarized from a baseline value of -82 mV to -65 mV; intracellular water had increased by 13%; and intracellular sodium and chloride contents had doubled. Eight rats were then given an infusion of very hypertonic saline (2400 mOsmole/kg, calculated osmolality) in a volume equal to only 10% of the volume of shed blood; another eight rats were given the equivalent amount of sodium and chloride in an isotonic solution (volume equal to 80% of shed blood). The mean arterial pressure in the rats that were given the very hypertonic saline returned to 81 mm Hg, compared to 55 mm Hg in the animals given normal saline. The membrane potentials in the hypertonic group polarized back to near normal- -78 mv--compared to no changes in the normal saline group. Intracellular water returned to preshock values in the hypertonic group as did intracellular sodium and chloride contents. Cellular contents in the normal saline group remained at shock levels. It was concluded that, in rats, infusion of small amounts of hypertonic saline can reverse some of the cellular abnormalities induced by hemorrhagic shock.

The effects of hypoproteinemia on blood-to-lymph fluid transport in sheep lung.

We studied the effects of reducing the plasma protein concentration on flow and composition of pulmonary lymph in 12 unanesthetized sheep. Whole blood was removed while red cells were returned and lactated Ringers was infused at a rate sufficient to maintain pulmonary vascular pressures at baseline values. A 44–54% reduction in plasma protein concentration resulted in a decrease in the plasma oncotic pressure from 18.6 ± 1.1 to 7.8 ± 0.9 mm Hg. Within an hour after plasmapheresis, lymph flows increased to a maximum of 4 times baseline. Subsequently, lymph flow gradually decreased and were close to baseline at 24 hours. The plasma-to-lymph oncotic gradient was reestablished in 5 hours due to decreased lymph protein. Maintained elevation of lymph flow with hydrostatic and oncotic gradients at baseline values suggest that the blood-to-lymph barrier offers leas resistance to fluid transport. The calculated filtration coefficient increased 2- to 3-fold after plasmapheresis. Protein clearances remained normally coupled to lymph flows. Thus the enhanced fluid transport cannot be attributed to a permeability change In the large pore pathways. Hypoproteinemia may alter the interstitial gel so that there is less resistance to fluid movement. Such changes in fluid conductivity between blood capillaries and lymphatics may augment the lymphatic safety factor against pulmonary edema during hypoproteinemia.

Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns

Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringers was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.

Wick sampling of interstitial fluid in rat skin: Further analysis and modifications of the method ☆

UNLABELLED We compared modifications of the wick technique for analysis of interstitial fluid in rat subcutis. Nylon wicks were implanted for 60 min in back skin of rats after anesthesia with pentobarbital or after sacrifice by potassium chloride injection. Wicks were implanted dry or loaded with saline or varied dilutions of rat serum. Implantation of dry wicks and wicks loaded with diluted serum in living, anesthetized animals produced similar results; the protein concentration of wick fluid averaged about 60% that of the plasma protein concentration. The saline loaded wicks produced wick fluid with a lower protein concentration, average about 45% that of plasma protein concentration. The lower concentrations apparently resulted from simple dilution. Wick fluid sampled from dead animals had similar total protein concentrations, but in the dead animals there was a lower concentration of the large plasma proteins and a relatively higher concentration of the smaller proteins. CONCLUSIONS Wick implantation in living animals causes a transitory inflammatory reaction and a decrease in the size selectivity of macromolecular sieving, but local osmotic forces bring about a concentration equilibrium with undisturbed interstitium. Implantation of dry wicks in subcutis either in vivo or post mortem provides a simple, direct method for sampling the total protein concentration and colloid osmotic pressure of interstitial fluid. Implantation of dry wicks postmortem permits measurement of individual component protein concentrations and evaluation of molecular selectivity between plasma and interstitium.

Effects of hypertonic saline on regional function and blood flow in canine hearts during acute coronary occlusion

Small-volume resuscitation using hypertonic saline (7.5%) is effective for various types of shock. Recently, hypertonic saline has been proposed for fluid management in patients with impaired cardiovascular function. Whether hypertonic saline is safe in the compromised heart during coronary occlusion is not known. We examined the effects of hypertonic saline at 4 mL · kg−1 on myocardial function and blood flow during acute coronary occlusion. In anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers. Myocardial contractility was assessed using percent of systolic shortenings measured in both normal or ischemic regions. Blood flow distribution was measured using radioactive microspheres. Percent of systolic shortening and blood flow in the normal myocardium, unaltered by coronary occlusion, increased significantly after hypertonic saline from 11.0 ± 1.1% to 13.7 ± 1.4% and from 120 ± 13 mL · min−1 · 100 g−1 to 169 ± 13 mL · min−1 · 100 g−1, respectively. In the ischemic myocardium, occlusion of the left anterior descending coronary artery markedly decreased percent of systolic shortening from 13.0 ± 1.2% to 9.3 ± .9% and blood flow from 98 ± 13 mL · min−1 · 100 g−1 to 19 ± 10 mL · min−1 · 100 g−1. At peak effect of hypertonic saline contractility and blood flow in the ischemic myocardium decreased to 7.4 ± .8% and 12 ± 5 mL · min−1 · 100 g−1, respectively. Five of the nine dogs developed premature ventricular beats during hypertonic saline infusion. However, no significant changes were observed when normal saline was given at equivalent volumes to hypertonic saline in six dogs. Hypertonic saline was associated with significant increases in heart rate (from 116 ± 3 beats · min−1 to 129 ± 5 beats · min−1) and cardiac output (from 2.54 ± .17 L · min−1 to 3.32 ± .26 L · min−1). Except for an improved perfusion in the skin, hepatic arterial, and coronary beds, blood flow to the muscle, spleen, jejunum, kidney, and brain was not significantly altered by hypertonic saline. Our data demonstrates variant effects of hypertonic saline on either normal or ischemic myocardium. Whereas contractile function and blood flow in the normal myocardium were improved after hypertonic saline infusion, further decreases in blood flow and contractile function in region distal to coronary occlusion could lead to worsening of ischemic injury. These data suggest that hypertonic saline may be deleterious in hearts with impaired contractile function caused by ischemia.

DETERMINANTS OF LYMPH FLOW AND COMPOSITION

Publisher Summary According to Starlings hypothesis, the rate of fluid movement across capillary walls depends on the balance of hydrostatic (P) and colloid osmotic (Π) forces. Under normal conditions, a small net loss of fluid from the capillaries is compensated for by lymphatic drainage of leaked fluid and solutes from the interstitium. Filtration rate and lymph flow can be increased by raising capillary hydrostatic pressure or by lowering plasma colloid osmotic pressure or by combinations of these procedures. The results of a study described in the chapter show that the increase in lymph flow for a given decrease in transcapillary colloid osmotic pressure difference is 1.4 to 1.8 times as great as that produced by an equivalent increase in hydrostatic pressure. For a given increase in lymph flow, decreasing colloid osmotic pressure produces a larger increase in blood–lymph protein clearance. Both these observations are contrary to expectation based on fluid and protein transport through large pores or channels, with low reflection coefficients for plasma proteins.

Laser Doppler velocimetry of tracheal blood flow in sheep

A laser-Doppler velocimetry (LDV) apparatus was adapted to assess sheep airway blood flow. The LDV signal obtained was compared to microsphere determinations of blood flow to tracheal tissues utilizing 15 microns radioactive microspheres injected before and after intubation and anesthesia, during hemorrhagic hypotension, and after reinfusion-resuscitation. During hemorrhagic hypotension, airway wall blood flow decreased to 16% of control by the microsphere method and to 30% by LDV. After reinfusion-resuscitation, airway wall blood flow increased over control values 40% and 33% by the two methods, respectively. Although at low flows LDV values were greater than microsphere determinations, the overall LDV recordings correlated with airway microsphere flow determinations of tracheal wall blood flow (R = 0.85) and tracheal mucosa flow (R = 0.81), but not with tracheal muscularis flow (R = 0.32). With certain but significant limitations, such as calibration in absolute units, stability of position placement, motion artifacts, and the effects of mechanical irritation-induced hyperemia, LDV represents a relatively noninvasive means for qualitatively evaluating changes in the microcirculatory blood flow of airway mucosa.

Small-Volume Resuscitation with Hypertonic Saline Dextran Solution

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 Ringers solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringers 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.