Michael P. Kinsky

Burn resuscitation: crystalloid versus colloid versus hypertonic saline hyperoncotic colloid in sheep.

OBJECTIVES The present study was undertaken to assess the fluid balance and hemodynamic effects during the first 8 hrs of resuscitation in animals with a large body surface area burn, using lactated Ringers solution, 6% hetastarch, and hypertonic saline dextran. DESIGN A prospective, blinded, controlled, terminal study, using anesthetized animals. The initial baseline period was followed by scald injury, and three different treatment regimens were administered from coded bags to achieve a physiologic end point. SETTING University laboratory. SUBJECTS Eighteen female sheep (35 to 45 kg) were anesthetized with isoflurane. INTERVENTIONS Test solutions (10 mL/kg of either lactated Ringers solution, hetastarch, or hypertonic saline dextran) were infused 30 mins after the scald injury at a rate to restore and maintain the baseline oxygen delivery (DO2) value. MEASUREMENTS AND MAIN RESULTS Cardiovascular hemodynamics, plasma sodium concentration, plasma colloid osmotic pressure, and fluid balance were measured before and after scalding and resuscitation. After the initial 10-mL/kg test solution dose was given, lactated Ringers solution was infused to achieve the same end point of baseline DO2 for the remainder of the 8 hrs. The scald caused an initial 30% reduction in cardiac output, a 20% reduction in mean arterial pressure, and 10% to 15% increase in hematocrit. All three test solutions restored and maintained baseline DO2 within 1 hr. However, hetastarch and hypertonic saline dextran reduced the net fluid volume over 8 hrs by 48% and 74%, respectively, compared with lactated Ringers solution. Edema in the burn wound was not affected by treatment, while hypertonic saline dextran reduced edema in nonburned skin compared with both lactated Ringers solution and hypertonic saline dextran. Plasma colloid osmotic pressure was significantly higher in the hetastarch and hypertonic saline dextran groups. A continuous decrease in plasma sodium concentrations from baseline values (140 to 145 mmol/L) was measured in the lactated Ringers solution and hetastarch groups (130 to 133 mmol/L) over 8 hrs. Plasma sodium concentrations in the group receiving hypertonic saline dextran were increased (150 to 155 mmol/L) at 4 hrs, but returned toward baseline by 8 hrs. CONCLUSIONS Net volume loading can be reduced markedly by initial resuscitation of large body surface area burn injury using a colloid (hetastarch), and can be further reduced by use of hypertonic saline colloid. Hyponatremia was apparent in the isotonic crystalloid- and colloid-treated animals, but not in those animals treated with hypertonic saline colloid.

Enteral resuscitation of burn shock using World Health Organization Oral Rehydration Solution : A potential solution for mass casualty care

Enteral resuscitation could provide a means to resuscitate burn shock when intravenous (IV) therapy is unavailable, such as in mass disasters. We evaluated the extent of intestinal absorption and resuscitative effects of World Health Organization Oral Rehydration Solution after a 40% TBSA burn in anesthetized swine compared with the IV infusion of lactated Ringer’s infused by Parkland formula. Plasma volume (PV) was measured using indocyanine green dye dilution. Intestinal absorption was assessed using phenol red as a nonabsorbable marker. Changes in hematocrit, hemodynamics, and measured PV showed equivalent resuscitative effects of enteral and IV resuscitation. The duodenal fluid absorption rate started at 77 ± 32 ml/hr per meter of intestine during the first hour and increased to 296 ± 40 ml/hr during the fourth hour of resuscitation, with a total of 93 ± 2% of World Health Organization Oral Rehydration Solution infused into the intestine being absorbed. Intestinal absorption rates after burn injury are sufficient to resuscitate a 40% TBSA burn.

Resuscitation of severe thermal injury with hypertonic saline dextran: effects on peripheral and visceral edema in sheep.

BACKGROUND Edema of tissue not directly injured by heat is a common complication after resuscitation of burn shock. Hypertonic 7.5% NaCl 6% dextran (HSD) infusion reduces early fluid requirements in burn shock, but the effects of HSD on peripheral and visceral tissue edema are not well-defined. METHODS We measured the microcirculatory absorptive pressures of burned and nonburned skin and tissue water content of skin and other tissues in anesthetized sheep after 70% to 85% total body surface area scald and resuscitation. Fluid infusion was initiated 30 minutes after injury using 10 mL/kg HSD (n = 11) or lactated Ringers (LR) (n = 12), with infusion rates titrated to restore and maintain preburn oxygen delivery (DO2). Thereafter, both groups received LR infusions as needed to maintain DO2 until the studys end at 8 hours. Colloid osmotic pressure was measured in plasma, and combined interstitial colloid osmotic and hydrostatic pressures were measured in skin. RESULTS Both treatments successfully restored DO2, but fluid requirements were less with the HSD group than with the LR group (43+/-19 mL/kg vs. 194+/-38 mL/kg, respectively, p < 0.05). The peripheral and visceral tissue water contents at 8 hours postinjury until the end of the study in both burn groups were significantly higher than in nonburn controls. However, HSD-treated sheep had significantly less water content in the colon (less 28%), liver (less 9%), pancreas (less 55%), skeletal muscle (less 21%), and nonburned skin (less 12%) compared with LR-treated sheep (p < 0.05 for each). HSD-treated sheep maintained significantly higher (3 to 5 mm Hg) plasma colloid osmotic pressure than LR-treated sheep. CONCLUSION There were no observed differences in edema in burn skin between the two treatment groups. The early volume-sparing effect of HSD and reduction in tissue edema are likely attributed to an increased extracellular osmolarity and a better maintenance of the plasma oncotic pressure.

Closed-Loop Control of Fluid Therapy for Treatment of Hypovolemia

Closed-loop algorithms and resuscitation systems are being developed to control IV infusion rate during early resuscitation of hypovolemia. Although several different physiologic variables have been suggested as an endpoint to guide fluid therapy, blood pressure remains the most used variable for the initial assessment of hemorrhagic shock and the treatment response to volume loading. Closed-loop algorithms use a controller function to alter infusion rate inversely to blood pressure. Studies in hemorrhaged conscious sheep suggest that: (1) a small reduction in target blood pressure can result in a significant reduction in volume requirement; (2) nonlinear algorithms may reduce the risk of increased internal bleeding during resuscitation; (3) algorithm control functions based on proportional-integral, fuzzy logic, or nonlinear decision tables were found to restore and maintain blood pressure equally well. Proportional-integral and fuzzy logic algorithms reduced mean fluid volume requirements compared with the nonlinear decision table; and (4) several algorithms have been constructed to the specific mechanism of injury and the volume expansion properties of different fluids. Closed-loop systems are undergoing translation from animal to patient studies. Future smart resuscitation systems will benefit from new noninvasive technologies for monitoring blood pressure and the development of computer controlled high flow intravenous pumps.

Muscle Protein Metabolism Responds Similarly to Exogenous Amino Acids in Healthy Younger and Older Adults during NO-Induced Hyperemia

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.

The role of interstitial starling forces in the pathogenesis of burn edema

The formation and sustainability of burn edema require substantial change in net microvascular forces. We directly measured interstitial hydrostatic pressure (Pi) and total interstitial absorptive pressure (Pi + IIi), in dermis of anesthetized sheep, before and after a 70% to 85% total body surface area scald and during fluid resuscitation. The most rapid change occurred in Pi in the burn wound, which rapidly decreased from its baseline value of approximately -2 mm Hg to -11 mm Hg in the first 5 minutes, and thereafter increased but remained approximately -4 mm Hg through 4 hours of resuscitation. Pi in nonburned skin slowly increased from its preburn level -2 mm Hg, to become positive +1 mm Hg after 4 hours of resuscitation. The total interstitial absorptive pressure, Pi + IIi, slowly declined similarly from 15 to 16 mm Hg to approximately 10 to 11 mm Hg over 6 hours of resuscitation in both burned and nonburned dermis. Taken together, these data suggest that the rapid formation of burn edema is the result of development of a negative Pi in the burn wound, and its sustainability is the result of a large increase in interstitial compliance. Edema in nonburned skin did not start until after fluid resuscitation was initiated, and then developed as the plasma oncotic pressure declined from 21 to 10 mm Hg.

Transpulmonary thermodilution for hemodynamic measurements in severely burned children

IntroductionMonitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients.MethodsThis prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra- and intergroup comparisons.ResultsSeventy-nine patients with a mean age (±SD) of 9 ± 5 years and a mean TBSA burn (±SD) of 64% ± 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury.ConclusionsContinuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay.

Effect of esmolol on fluid therapy in normovolemia and hypovolemia.

ABSTRACT &bgr;-Adrenergic agonists can enhance vascular volume expansion after a fluid bolus. The present study addresses how the &bgr;-adrenergic antagonist esmolol influences volume expansion and fluid balance during normovolemia (series 1) and hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For series 1, continuous infusion of 50 to 100 µg·kg−1·min−1 esmolol (n = 6) or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg−1 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with 50 to 100 µg·kg−1·min−1 esmolol (n = 6) or control (no drug; n = 6) 30 min before a-20 mL kg−1 hemorrhage. Fluid resuscitation (0.9% NaCl) was begun 30 min after hemorrhage. The 24-mL kg−1 20-min bolus was followed by titrated fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate changes in plasma volume (&Dgr;PV), extravascular volume (&Dgr;EVV = fluid in − urinary output − &Dgr;PV), volume expansion efficiency (VEE = fluid in / &Dgr;PV), and fluid distribution ratio (&Dgr;PV/&Dgr;EVV). Hemodynamics for both series were similar with the exception of heart rate. In series 1, peak &Dgr;PV was 9.1 ± 1.0 mL kg−1 in control and 3.7 ± 1.0 mL kg−1 at study end. Esmolol resulted in a lower peak &Dgr;PV (6.4 ± 2.0 mL kg−1) and a negative &Dgr;PV (−0.4 ± 0.6 mL kg−1) at studys end. Urinary output was lower, and EVV was greater with esmolol. In series 2, esmolol increased fluid requirements (67 ± 7 mL kg−1) compared with control (54 ± 5 mL kg−1). Esmolol reduced &Dgr;PV/&Dgr;EVV. These data suggest that esmolol impairs the vascular retention of fluid and may increase the amount of volume support during fluid resuscitation.

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 ± 6.2 mL/kg for HPY and 39.4 ± 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Burn-Induced Cardiac Dysfunction Increases Length of Stay in Pediatric Burn Patients

The aim of this study was to evaluate cardiac function and clinical outcomes in perioperative pediatric burn patients. Transesophageal echocardiography data were collected on 40 patients from 2004 to 2007. Of the 40 patients who received exams, a complete set of cardiac parameters and outcome variables was obtained in 26 patients. The mean age of the patients was 9.7 ± 0.9 years, and the mean TBSA burn size was 64 ± 3%. Patients were divided into two groups based on systolic function. One group represented patients with ejection fractions of >50% and the other ⩽50%. Clinical variables were then compared among the groups. In our cohort, systolic dysfunction was observed in 62% of patients (EF ⩽ 50%). Systolic dysfunction was associated with a statistically significant increase in number of surgeries, ventilator days, and length of stay in the intensive care unit. The length of stay in patients with preserved systolic function and those with systolic dysfunction was 34.3 ± 3.3 days and 67.2 ± 4.0 days, respectively. Diastolic function measurements were obtained in 65%, and 88% had evidence of diastolic dysfunction. Diastolic dysfunction was not associated with any statistically significant correlations. This study lends evidence to the well-supported basic science models showing cardiac dysfunction after burns. Additionally, it shows that cardiac dysfunction can have clinical consequences. To our knowledge, this is the first study that shows the clinical sequelae of systolic dysfunction in the perioperative pediatric burn population.