Fluid shift is moderate and short-lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets.

BACKGROUND: Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. METHODS: Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. RESULTS: Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. CONCLUSION: Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Porcine surfactant (Curosurf) for acute respiratory failure after near-drowning in 12 year old.

This case report describes rapid and persistent improvement after one single dose of porcine surfactant (Curosurf) 0.5 ml/kg(-1) (40 mg/kg) intratracheally for adult respiratory distress syndrome (ARDS) with severe oxygenation failure 8 h after freshwater near-drowning in a 12-year-old girl.

Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

OBJECTIVE: Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass. METHODS: A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated. RESULTS: Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study. CONCLUSION: Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

[Outbreak of multiresistant Acinetobacter baumannii infection]. / Utbrudd av infeksjon med multiresistent acinetobacter baumannii.

BACKGROUND: Nosocomial infections caused by multiresistant gram-negative bacteria represent an increasing problem, especially among intensive care patients. A serious outbreak of infection caused by multi-resistant Acinetobacter baumannii occurred in four burn patients. Acinetobacter is a gram-negative coccibacilli which is widespread in nature, and has been reported as an increasing problem in critically ill patients. MATERIALS AND METHODS: The outbreak strain was introduced from Alicante, Spain, by a transferred patient. This strain was resistant to all commonly available systemic antibiotics (including the karbapenems and all aminoglycosides), and sensitive only to polymyxin B. Two patients were critically ill, one of them died in septic shock. RESULTS: The ward was closed for admission of new patients and hygiene precautions were strengthened. Extensive testing of staff and equipment revealed multi-resistant A baumannii on a shower trolley shared by several patients. The outbreak strain was also identified by restriction endonuclease analysis. The patients were kept strictly isolated until their burn wounds were sufficiently healed to allow them to be discharged to their homes. INTERPRETATION: Following discharge of the last patient and extensive cleaning and disinfection of the entire ward, the particularly resistant strain has not reoccurred. Still, this experience may warrant screening for multiresistant gram-negative rods in patients transferred from regions where broad resistance to antibiotics is a common problem.

Markedly increased lymphatic removal of hyaluronan from skin after major thermal injury.

Hyaluronam (HYA) (formerly hyaluronic acid) is an important constituent of the interstitial matrix in skin. Following major burn injury plasma HYA is known to increase markedly. The present study investigated to what extent the lymphatic removal of HYA from skin is affected following major burn injuries. Under ketamine anaesthesia a 30 per cent full thickness scald injury was inflicted on sheep previously provided with a chronic prefemoral lymph fistula. Animals were resuscitated for 24 h using lactated Ringer's infusion as needed to restore and maintain cardiac output within +/- 10 per cent of baseline. Following burn injury, lymph flow from thermally injured tissue gradually increased to 10-25 times above baseline. The baseline HYA concentration in lymph was 4.3 +/- 1.1 micrograms/ml; the HYA concentration in lymph was not significantly altered postinjury. The lymphatic HYA flux (flow x concentration) increased postinjury to 5-30 times control. The HYA concentration in plasma was 162 +/- 12 ng/ml at baseline; postinjury plasma HYA peaked at two to three times baseline at 4-8 h after the injury. At 24 h postinjury plasma HYA was reduced compared to baseline. In conclusion, after major burn injury the lymphatic transport of HYA from the injured area into the systemic circulation increased markedly, leading to elevated plasma concentrations of this high molecular weight connective tissue component.

Retention and distribution of polygeline (Haemaccel) in the rat.

The plasma substitute polygeline (Haemaccel registered) contains a large fraction of molecules sufficiently small to cross the capillary and glomerular membranes. Plasma volume expansion, tissue extravasation and renal elimination of this artificial colloid were quantified using 125I-labelled polygeline molecules. In pentobarbital anaesthetized rats, either 10 ml 3.5% polygeline (n = 8) or 10 ml 0.9% saline (n = 8) was infused intravenously over 60 min. The plasma volume was assessed by the 3 min distribution volume for I-albumin and the plasma volume changes over time were calculated from erythrocyte volume fractions. The plasma volume increased by 4.6 (2.0) ml (mean (SD)) at the end of the Haemaccel infusion compared with 2.1 (1.8) ml after the saline infusion (P = 0.02). One hour later the increase was 2.4 (1.5) and 1.6 (1.0) ml respectively, not significantly different (P = 0.20). Extravasation of labelled polygeline was greatest in the kidney, possibly due to cellular uptake. Skin and skeletal muscle contained 4-5 times more polygeline than could be attributed to intravascular radioactivity, but still uptake in these tissues did not reach one percent of the amount injected. Following a 60 min infusion and a 60 min interval, 23 (4)% of the polygeline was recovered intravascularly, 43 (9)% had been excreted in urine, leaving 33% to other compartments. Thus, more polygeline was distributed to the interstitium than remained in the circulation. This calls for further investigations into the handling and effect of polygeline in this extravascular compartment.

Fluid shifts following 7% hypertonic saline (2400 mosmol/L) infusion.

Small volumes of hyperosmolar saline solutions may rapidly improve MAP and CO in hemorrhagic shock. In the present study, the effects of infusion of 7% NaCl on interstitial fluid volume and intracellular fluid volume were determined. In anesthetized, normovolemic rats either 7% NaCl (1.1 mL/100 g, intravenously), acetated Ringer's solution (10 mL/100 g), or no fluid (controls) were infused and extracellular volume (ECV) and plasma volume were determined in samples from skin, skeletal muscle, small intestine, liver, and lung. Intracellular volume was determined as local tissue water content minus ECV. Extracellular fluid volumes were 21.1 +/- .6 mL/ 100 g(mean +/- SEM; n = 6) (control animals), 26.1 +/- .4 mL/100 g (following 7% NaCl) (p < .05), and 32.8 +/- .5 mL/100 g (following Ringer's) (p < .05). Following 7% NaCl ECV increased by four to five times the infused volume. With 7% NaCl ECV in skin, muscle and intestine increased significantly, whereas cell volume was reduced by 10% in muscle and liver. Skeletal muscle, constituting > 40% of body mass with a large cell volume, was the main source for fluid mobilized by administration of 7% NaCl.

[Patients with burns admitted to hospitals in 1992. Fewer cases and shorter length of stay also in Norway?]. / Brannskadede innlagt i sykehus i 1992. Faerre skadetilfeller og kortere liggetid også i Norge?

Patients admitted for care of acute burns in Norway in 1992 were compared with patients in an earlier national survey in 1977. In 1992, 635 patients were admitted for acute burns in Norway, 20% less than in 1977. 8,975 hospital days were spent on care of acute burns, a 45% reduction compared with 1977. 58 patients (10% of all burn cases admitted to hospital) were referred to the National Burn Centre in Bergen. The number of deaths from fire and burn injury was similar to the number in 1977 (68 persons). Despite a moderate reduction in the total number of burns we found no evidence of a significant reduction in the number of severe burns. To achieve optimal functional and cosmetic results, extensive burns still deserve the special care offered in a regional Burn Centre.

Increased plasma concentrations of hyaluronan after major thermal injury in the rat.

Hyaluronan (HYA) is an ubiquitous polysaccharide in connective tissue interstitium; its normal plasma concentration is in the nanogram/ml range. Following major burn injury in sheep, plasma HYA can increase to levels tenfold greater than normal. The present study aimed to determine the effects of major cutaneous burns on plasma HYA concentration in rat, since in this species, the HYA elimination kinetics may better resemble those in man. Thermal injury did not alter the weight-average molecular weight of HYA in skin. HYA concentration in plasma was 46 +/- 4 ng/ml (mean +/- SEM) in controls. Three hours after scald burns to 40% of the body surface area, plasma HYA was 61 +/- 10 ng/ml in unresuscitated animals (P less than 0.1 vs. controls). After fluid replacement by lactated Ringer's plasma HYA was 75 +/- 8 ng/ml (P less than 0.01 vs. control), whereas plasma infusion prevented the elevation of plasma HYA. HYA also increased significantly after lactated Ringer's infusion in noninjured animals. The increased plasma concentration of HYA after major burns is probably a consequence of increased lymph flow, increasing its transport from skin interstitium. Possibly, plasma concentrations of connective tissue components may be used as indicators of the severity and extent of burn injuries.

Pathogenesis of edema formation in burn injuries.

One of the obvious acute features of cutaneous thermal injury is the swelling of the involved tissue. This swelling is caused by a fluid shift from circulating plasma. Along with the evolution of intravenous fluid therapy in trauma and surgery, the implementation of such therapy to burn victims has improved survival. Edema generation aggravated by fluid therapy may, however, represent a source of increased morbidity. This paper presents a review of the literature on postburn edema generation, focusing mainly on fluid physiology. It is well documented that fluid is lost from the circulation into burned tissue because of a moderate increase in capillary permeability to fluid and macromolecules and a modest increase in hydrostatic pressure inside the perfusing microvessels. Recently it was discovered that a very negative interstitial pressure develops in thermally injured skin. This pressure constitutes a strong "suction" adding markedly to the edema generating effect of increased capillary permeability and pressure.

Elevated hyaluronan blood concentrations in severely burned patients.

Hyaluronan (HYA) is a polysaccharide found in the interstitial matrix in most tissues. HYA is removed by lymphatic drainage and degraded in local lymph nodes and in the liver. Its normal concentration in human plasma is very low (10-100 micrograms l-1). Following major burn injury in sheep plasma HYA can increase to levels tenfold greater than normal. In the present study, serum HYA concentrations were determined in 10 severely burned patients (burn size: 28 +/- 5% of body surface area (mean +/- SEM)). Serum HYA concentration was 206 +/- 71 micrograms l-1 at 24 h post-injury, twice the upper normal HYA concentration, and remained moderately elevated for the first week post-injury. It appears that mobilization and transport of HYA from the tissues is increased after thermal injury. Increased systemic concentrations of an interstitial matrix component have not previously been reported in burn patients. Possibly, plasma concentrations of connective tissue components might serve as indicators of the severity and extent of burn injuries.

Microvascular exchange during burn injury: IV. Fluid resuscitation model.

The present work is a continuation of studies concerned with mathematical modelling and simulation of microvascular fluid and protein exchange following burn injuries [Bert et al.: Circulatory Shock 28: 199-219, 1989: Bowen et al.: Circulatory Shock 28: 221-233, 1989]. The model has been extended to include the effects of different types of fluid resuscitation on the circulatory and microvascular exchange systems. The model and a statistical fitting procedure were used to find the ranges of fitting parameter values that best describe the changes in interstitial fluid volume and protein mass as well as transcapillary protein extravasation for three sets of experiments (no resuscitation, resuscitation with Ringer's or resuscitation with plasma). Typical changes in mass exchange related parameters postburn that resulted in simulation predictions which were a good fit to the experimental data include: an increase in the large pore pathway for protein of 100 times in the injured skin and 5 times in non-injured skin and skeletal muscle, an increase in fluid filtration coefficients in injured skin of 10 times and an instantaneous decrease of 50% in the area available for exchange in injured skin at the time of the burn.

Increased hyaluronan flux from skin following burn injury.

Hyaluronan (formerly hyaluronic acid) is an important constituent of the interstitial matrix in skin. Following major burn injury in animal models, plasma hyaluronan can increase to levels 10-fold greater than normal. The present experiments were designed to determine whether this is a result of the increased lymph flow (QL) accompanying the injury or of an increased release of hyaluronan from the burned skin and subcutaneous tissue. The lateral saphenous vein and a prenodal lymphatic were cannulated in the hindpaw of five anesthetized canines. Hindpaw venous pressure was elevated until the total protein concentration in lymph declined to steady-state levels, and QL and hyaluronan flux (QL X [hyaluronan]) was measured. A minor burn was inflicted by immersion of the paw into 100 degrees C water for five sec, and measurements were repeated at regular intervals for a minimum of 4 hr. Burn injury resulted in significant and persistent increases in QL (154 +/- 61 microliters/min versus 562 +/- 105 microliters/min 4 hr postburn) and lymph total protein concentration (1.34 +/- 0.04 g/dl versus 4.08 +/- 0.18 g/dl 4 hr postburn), while lymph hyaluronan concentration fell (3.01 +/- 0.20 micrograms/ml versus 2.1 +/- 0.16 micrograms/ml 4 hr postburn). The resultant increase in hyaluronan flux (0.42 +/- 0.13 microgram/min versus 1.17 +/- 0.22 microgram/min 4 hr postburn) appears to be a function of lymph flow rather than burn-induced release of skin hyaluronan. Hence, the increased plasma concentration of hyaluronan following major burns is likely a consequence of increased lymph flow from the site of injury.

Marked increase of plasma hyaluronan after major thermal injury and infusion therapy.

Hyaluronan (HYA) is an important structural element in skin and is presumably participating in regulation of the interstitial fluid volume. HYA is transported via the lymphatics from the tissues to the blood, where its concentration is normally very low. Fluid flux through the interstitium is markedly increased after thermal injury. The present study was performed to determine whether major thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep subjected to 40% BSA full-thickness scald burns, plasma HYA concentration increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than 0.01). To clarify whether this rise represented an increased "washout" of interstitial HYA, attributable either to the burn injury or the subsequent fluid therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3 times baseline. Lung lymph flow and its concentration of HYA increased, leading to an increase in the lymphatic flux of HYA to 10-20 times baseline. In peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated Ringer's markedly increased lymphatic removal of HYA. However, plasma concentrations of HYA were 3 times higher after thermal injury than following fluid challenge alone, suggesting that thermal injury per se may also increase input of HYA into the systemic circulation.

Thermal skin injury: effect of fluid therapy on the transcapillary colloid osmotic gradient.

The effects of fluid therapy on interstitial colloid osmotic and hydrostatic pressures in thermally injured skin were investigated in anesthetized rats subjected to full-thickness scald burns to 40% of the body surface area and resuscitation for 3 hr by either lactated Ringer's or plasma. Interstitial fluid hydrostatic pressure (Pif) was reduced from -2 mm Hg to -20 to -40 mm Hg after injury, which will profoundly increase transcapillary filtration. Following the onset of fluid therapy, Pif increased to slightly positive values. In control, colloid osmotic pressure in plasma (COPp) was 20.6 +/- 0.4 mm Hg and in interstitial fluid (COPif) 13.7 +/- 0.3 mm Hg (means +/- SEM). The transcapillary oncotic pressure gradient (COPgrad = COPp-COPif) was 6.9 +/- 0.4 mm Hg. Following nonresuscitated thermal injury, COPp declined to 18-19 mm Hg (P less than 0.05) and COPif was reduced to 10.4 +/- 0.5 mm Hg (P less than 0.05). Fluid therapy by lactated Ringer's markedly reduced COPp (12.3 +/- 0.3 mm Hg; P less than 0.05), and COPgrad was almost abolished (2.6 +/- 0.7 mm Hg; P less than 0.05). In contrast, plasma infusion maintained COPp, whereas COPgrad increased significantly (11.1 +/- 1.2 mm Hg; P less than 0.05). Noncolloid saline solutions have been preferred for the initial fluid therapy for burns. The present study provides evidence that this will reduce both COPp and COPgrad, a situation in which edema formation will be favored.

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 Ringer's 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.

Mechanisms behind increased dermal imbibition pressure in acute burn edema.

We have measured tissue pressures in excised rat skin subjected to in vitro burn injury and investigated the mechanisms behind the increased imbibition (swelling) pressure in burned skin. Skin pieces wrapped in aluminum paper were immersed into boiling hot water for 10, 30, or 60 s. Dermal imbibition pressure was measured with micropipettes and tissue osmometry as interstitial fluid hydrostatic pressure (Pif) and/or interstitial fluid colloid osmotic pressure (COPif). COPif was also measured in interstitial fluid sampled with intradermal wicks. Control values of Pif (micropipettes) and of COPif (wick fluid) averaged -1.5 mmHg and -17.5 mmHg, respectively. An increase in imbibition pressure was seen after thermal injury. After 10 s of heat exposure, the imbibition pressure gain was mainly due to a strongly negative hydrostatic pressure (Pif mean value -33.3 mmHg). Pif became slightly positive and COPif increasingly negative after longer exposure (mean Pif 0.3 and mean COPif -133 mmHg after 60-s exposure). Collagen degradation and water solubility increased with extension of the heat exposure time. Thermal degradation of collagen seems to be the main mechanism responsible for the generation of increased imbibition pressure.

Thermal skin injury: I. Acute hemodynamic effects of fluid resuscitation with lactated Ringer's, plasma, and hypertonic saline (2,400 mosmol/l) in the rat.

Heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and cardiac index (CI) were measured in anesthetized rats subjected to a 40% body surface area full-thickness scald burn. Postburn intravenous fluid therapy with lactated Ringer's (5 ml/hr), plasma (2.5 ml/hr), or very hypertonic saline (2,400 mosmol/l) (0.75 ml/hr) was compared to unburned or burned, untreated controls. HR and CVP were not influenced significantly by thermal injury. MAP decreased steadily in the untreated group from 110 mmHg to 80 mmHg at 3 hr postburn. In the fluid-treated groups MAP did not change significantly. During the first 15 min postburn, CI was reduced to 58-71% of control values (P less than 0.01). CI increased during Ringer's and plasma infusion to 74-80% of control values (P less than 0.02 vs. unburned). Despite infusion therapy, hematocrit increased from 48 to 52%, clearly less than in the unresuscitated group (increase from 48 to 58%). Theoretically, the 2,400 mosmol/l saline would expand extracellular volume by five to six times the infused volume. Still, CI was reduced by 55% at 3 hr postburn in the hypertonic saline as well as in the burned, untreated group (P less than 0.001 vs. unburned). The low CI was mainly due to a reduced stroke volume.