Early Postburn Period Research Articles

Pilot study into the IgG1 and IgG2 subclass response to polyvalent pseudomonas vaccine in burned adults

The IgG1 and IgG2 subclass response to thermal injury has been measured in a group of eight burned adults who received a single intramuscular injection of 0.5 ml of polyvalent pseudomonas vaccine (PPV), within hours of burn injury. The response in three of these patients is compared with the response in three matched patients who did not receive the vaccine. This single dose regimen of PPV did not appear to stimulate the early production of IgG1 or IgG2 and if subclass deficiency contributes to the risk of sepsis or toxin-mediated disease, as previous workers have established (Schur et al., 1970; Oxelius et al., 1981), then there is no apparent benefit in active immunization to reduce the risk in the early postburn period.

The Relationship between the Percentage of Circulating B Cells, Corticosteroid Levels, and Other Immunologic Parameters in Thermally Injured Patients

Thermal injury is known to induce alterations in the immune system, but the precise mechanisms have yet to be elucidated. We investigated the temporal relationship between serum and urine corticosteroid levels, the number of circulating B cells, serum immunoglobulin levels, and delayed hypersensitivity reactions in the postburn period. Fifteen adult patients (mean age, 44 years) admitted with thermal burns greater than 20% body surface area (BSA) (mean, 50%) were evaluated during four postburn periods. Using a bacterial adherence assay in blood smears, we observed an increased percentage of B lymphocytes (20.3%) in the early postburn period compared to normal controls obtained during the same time period (13.1%). The percentage of B cells gradually decreased during the subsequent 4 weeks and was not influenced by the eventual clinical outcome. The changes in B-cell percentage were paralleled by changes in the level of urine 17-hydroxysteroids. Serum IgG concentrations were low during the initial postburn period in survivors and nonsurvivors and returned to normal and above-normal levels in the late postburn period in both groups. The delayed hypersensitivity skin test reactions were also depressed in the immediate postburn period and returned to normal only in the surviving group at the end of the second postburn week. We speculate that the increased endogenous secretion of stress hormones results in an increase in circulating B cells secondary to their release from lymphoid organs and that the normalization of hormone levels as wound healing ensued was associated with the return of B cells to the lymphoid organs. This lymphocyte redistribution may result in polyclonal cellular interactions, with subsequent B-cell activation, and increased IgG production.

The decrease in peripheral blood CD4+ T cells following thermal injury in humans can be accounted for by a concomitant decrease in suppressor-inducer CD4+ T cells as assessed using anti-CD45R

Using single- and two-color fluorescence flow cytometry, 10 thermally injured human subjects were assessed over time for both percentages and absolute numbers of lymphocytes comprising peripheral blood lymphocyte subpopulations. The CD3+ lymphocyte percentage decreased significantly in the early postburn period, and this decrease could be accounted for entirely by a concomitant decrease in the CD4+ lymphocyte percentage. Further, the decline in CD4+ percentage was due to a specific decrease in the suppressor-inducer subset of CD4 as defined using anti-CD45R. No change in the helper-effector subset of CD4 was noted. The percentage of CD8+ lymphocytes did not change significantly at any time postburn nor did subsets of CD8 as defined using anti-CD11. Numerical changes in lymphocyte subsets were dominated by a general lymphopenia occurring on Day 4 following injury. However, suppressor-inducer ( CD4+ CD45R+ ) T cells also decreased significantly on postburn Day 1. These results further elucidate phenotypic changes in immunoregulatory subsets following major injury and suggest a possible basis for depressed autologous mixed lymphocyte responsiveness of burn patient T cells, one of the functional immunologic defects associated with severe injury.

Analysis of altered capillary pressure and permeability after thermal injury

In order to investigate the effects of thermal injury on microvascular hemodynamics and permeability, hindpaw arterial ( P A), venous ( P V), and capillary ( P C) pressures, blood ( Q B) and lymph ( Q L) flows, and lymph ( C L) and plasma ( C P) total protein concentrations were measured before and for 3 hr after a 10-sec 100°C scald burn in 11 dogs. Prior to injury in eight experiments (Group I—permeability analysis) venous pressure was elevated by outflow restriction until the minimal C L C P was obtained. In three experiments (Group II—hemodynamic analysis) outflow was not restricted. Lymph and plasma protein fractions ranging in size from 37 to 120 Å were measured using gradient gel electrophoresis and capillary equivalent pore sizes were calculated. In the early postburn period, P C increased from 24 ± 2 (mean ± SE)to 47 ± 5 mm Hg ( P < 0.05) and precapillary resistance ( R A) decreased from 6.6 ± 0.2 to 2.5 ± 0.2 mm Hg/ml/min/100 g ( P < 0.05) while postcapillary resistance ( R V) remained unchanged. Pre- to postcapillary resistance ( R A R V ) fell by 74%. The reflection coefficient for total proteins (calculated as σ = 1 − C L C P ) decreased from 0.87 ± 0.01 to 0.45 ± 0.02 ( P < 0.01). Permeability of the postburn capillary endothelium was described by using two populations of equivalent pores. Preburn pore radii were 50 and 300 Å with 13% of the capillary filtrate passing through the large pores. Pore radii increased after injury to 70 and 400 Å with 49% of the filtrate passing through the large pores. The postburn total tissue filtration coefficient ( K f) increased to 2.4 times the control. Over the first 3 hr postburn, 53% of the increase in capillary filtration was attributable to increased capillary pressure and 47% to increased permeability. We conclude that the early rapid edema formation following thermal injury is the result of marked increases in both capillary filtration pressure and filtration through large nonsieving pores.

The effect of rapid resuscitation upon cardiac index following thermal trauma in a porcine model.

Minipigs were divided into four experimental groups: nonburned control (C); burn, minimal resuscitation (MR); burn, standard resuscitation (SR); and burn, rapid resuscitation (RR). Resuscitation was begun 30 minutes postburn and hemodynamics were measured through 24 hours postburn. At 30 minutes postburn, the three burn groups demonstrated a significant decrease in cardiac index % (CI%). At 1 1/2 hours postburn, the RR group CI% was significantly greater than for the SR group and not significantly different from that of controls. At 2 hours postburn, fluid was abruptly decreased in the RR group and the salutary effect on CI promptly dissipated. In this model, the early decrement in CI following thermal injury is responsive to rapid resuscitation, concluding that the etiology of decreased CI following thermal trauma is at least partially due to inadequate volumes of fluid administration in the early postburn period.

Protein loss across burn wounds.

One factor contributing to negative nitrogen balance in burned patients is protein loss through the burn wound. There is, however, little information on the amount and type of protein lost by this route. This study was designed to quantitate protein loss through burn wounds. Multiple full- and partial-thickness burns on 29 patients were studied. Sampled burn sites were dried and occlusive sponge dressings (2'' X 2'') were applied and left in place for 1 hour. The central 1 square-inch portion of the dressing was then removed, rinsed in distilled water, and total protein, albumin, and globulin were measured in the water wash. Considerable protein losses were measured. These losses were greatest in the first 3 postburn days, being somewhat greater in full-thickness burns (0.98 +/- 0.82 mg/cm2/hr) compared to partial-thickness burns (0.59 +/- 0.41 mg/cm2/hr) during this period mean +/- SD). Subsequent to the first 3 postburn days, protein loss in all burn types decreased to a relatively steady rate of loss of approximately 0.25 mg/cm2/hr. Based upon these data, average daily protein losses during the first postburn week can be estimated by the following equation: 24-hour protein loss through burn surface (gm) = 1.2 X body surface area (m2) X % burn (%). On subsequent days, protein is lost at approximately half this rate. These data demonstrate significant protein losses through burn wounds greater than recent studies have considered. It is possible that inadequate nutritional replacement of these protein losses is partly responsible for the marked negative nitrogen balance of the early postburn period.

The effect of route of nutrient administration on the nutritional state, catabolic hormone secretion, and gut mucosal integrity after burn injury.

So that the efficacy of route of nutrient administration in thermal injury could be determined, a comparison was made between immediate enteral vs parenteral feedings in burned guinea pigs. Thirty-five guinea pigs underwent both catheter gastrostomy and jugular vein catheterization. On postoperative day 8, burned animals [30% total body surface area (TBSA)] were divided into an intragastrically (ig) fed group (N = 14) and a parenterally (iv) fed group (N = 14). Animals in each group received 175 kcal/kg/day with a solution of identical nutrient value beginning 2 hr after burn. The body weight change until postburn day (PBD) 8 and the average nitrogen balance were significantly better in the ig group than in the iv group. Values were also higher for the iv group than for the ig group in the early postburn period for urinary vanillyl mandelic acid (VMA) (p less than 0.05), plasma cortisol (p less than 0.05), and plasma glucagon (p less than 0.05). Also, the iv group showed reduced mucosal weight and thickness compared to the ig group on PBD 1 (p less than 0.02). There were significant negative correlations between VMA excretion and body weight change, and between plasma cortisol and jejunal mucosal structure (thickness and weight). These findings suggest that immediate postburn enteral nutrition can provide better nutritional support than parenteral nutrition through the maintenance of gut mucosal integrity and the prevention of increased secretion of catabolic hormones.

Serum lipid peroxide levels of patients suffering from thermal injury

Lipid peroxide levels and activities of various enzymes were examined in sera from five thermally injured patients. In all patients examined, serum lipid peroxide levels were increased in the early post-burn period, and thereafter activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase and lactate dehydrogenase in the sera became elevated in most patients. From these observations, it is considered that increased lipid peroxides in the bloodstream during the early post-burn period would cause damage to various organs, permitting the leakage of the enzymes into the blood. These results support the view that lipid peroxide may be regarded as a ‘burn toxin’.

The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model.

A number of vasoactive substances, including serotonin, have been implicated in the pathophysiology of burn shock. Ketanserin, a specific serotonin antagonist, was investigated in a porcine burn shock model. Fifteen swine were given a mean 44% total body surface area full-thickness scald burn and received fluid resuscitation with Ringer's lactate for 24 hours postburn. The swine were divided into three groups: Group I (control group) received no ketanserin; Group II received ketanserin as a single intramuscular dose preburn and continuously via intravenous drip postburn; and Group III received ketanserin continuously via intravenous drip postburn only. The ketanserin-treated groups demonstrated improved cardiac index, decreased pulmonary artery pressures, and smaller arteriovenous oxygen content differences compared to the control group in the early postburn period. Ketanserin should be investigated further as a possible adjunctive therapeutic agent during burn shock resuscitation.

Fluid Resuscitation After Major Burns

IN THE 1940s, hypovolemic shock in the early postburn period was the leading cause of death after severe burn injury. Today, with our current knowledge of the massive fluid shifts and vascular changes that occur, early mortality has decreased considerably. The failure rate for adequate volume restoration is less than 5%, even for deep burns involving up to 85% of the total body skin surface. 1 The problem of nonreversible shock has now been replaced by that of generalized burn edema formation, a problem clearly less lethal but one that can result in serious morbidity. Tissue ischemia due to an increase in interstitial pressure is one complication of edema. 2 Pulmonary insufficiency, as a result of both a decrease in chest wall compliance from tissue edema and an increase in blood volume during edema mobilization, is another potential complication. Hypovolemia can be corrected and edema at least partially controlled, however,

Research:Protection from Catabolism in Major Burns: A New Formula for the Immediate Enteral Feeding of Burn Patients

The hypermetabolic state of patients with a major burn indicates an immediate need for calories and protein. These patients are at high risk for sepsis with intravenous hyperalimentation (IVH), and enteral feedings are not attempted during the resuscitation period, usually lasting 7 to 10 days. Twelve patients with major burns (40% to 70%) were fed nasoduodenally in the early postburn period with a new solution (3.5% Aminosyn, 25% Polycose, with appropriate addition of electrolytes and vitamins based on IVH solutions). All patients reached positive nitrogen balance in 9.8 ± 2.3 days and tolerated the enteral feeding extremely well, with no complaints of bloating or diarrhea. Metabolic assessment showed remarkable stability in these patients; the characteristic signs of hypermetabolism such as hyperglycemia and hypo-or hyperinsulinemia were absent. Furthermore, there was no persistent neutrophilia or leukocytosis, and a significant (P 0.001) increase in absolute lymphocytes between Day 0 and Day 14 of feeding. These data indicate that early enteral feeding of Polycose: Aminosyn is safe and well tolerated and that the small intestine will absorb nutrients readily in the early postburn period, leading to positive nitrogen balance, preventing loss of serum protein levels, assisting in the maintenance of normal carbohydrate metabolism, and restoring granulocytes and lymphocytes to normal ratios.

Evaluation of the burn wound with perfusion fluorometry.

Determination of depth of burn injury using vital dyes has been unsatisfactory. The present study evaluated the ability of the fiberoptic perfusion fluorometer to assess the depth of burn in the early postburn period. Sixty-three burns were examined with the fluorometer after intravenous administration of sodium fluorescein. The fluorescein kinetics were monitored for 1 hour within the first 48 hours and again between the third and sixth days postburn. The rate of fluorescein uptake and burn wound fluorescence was determined and compared to that of normal unburned skin. Depth of burn was confirmed by biopsy and healing characteristics. Fluorometric analysis during both study periods consistently distinguished between partial-thickness and full-thickness burns. Partial-thickness burns uniformly exhibited fluorescence within 10 minutes; full-thickness burns showed nil fluorescence. None of the patients experienced a change in skin color or complications from the small dose of fluorescein given.

Effect of thermal injury on lipid peroxide levels of rat

Since the report of Cannon and Bayliss (1) who believed that fluid loss from circulation was not sufficient to account for the circulatory failure commonly seen in battle casualties, occurrence of “toxic factor” has gathered much attention. In fact, in these cases fluid therapy is very successful in acute phase, but late death often occurs. Accordingly, many investigations on toxic factor after burn injury have been carried out. Among them, the following reports drew our attention. Allgöwer et al. (2) claimed to have identified the toxin as a lipid-protein polymer formed from a component of cell walls of the skin. Helmkamp et al. (3) found significant reduction in the levels of polyunsaturated fatty acids such as linoleate, arachidonate, and docosahexaenoate in red cell membrane phospholipid of severely burned humans. Loebl et al. (4) suggested that erythrocyte destruction in early postburn period would be due to a substance circulating in thermally injured patients. Rai and Courtemanche (5) described that with an increase in burn index, the fall in vitamin A level became greater. Sugiyama et al. (6) recently reported that extensive release of prostaglandins into the blister a few hours after burn injury would partly explain general symptoms of the burn syndrome. From these reports, we suspected that burn toxin might be similar to lipid peroxides. In the present study, therefore, the levels of lipid peroxides in animal tissues and serum of postburn period were measured.

How different therapeutic measures can effect host defence in experimental burns

TWELVE years ago Dr Wesley Alexander, the chairman of this session, emphasized that it is important to determine the effects of immunological defects on burn victims before one can hope for any rational therapy (Alexander and Moncrief, 1966). We have studied cell proliferation and cell injury in different organs post burn. However, we have concentrated on a narrow field of the host defence mechanisms, the granulocytes, using them as an indicator in evaluating the effects of different therapeutic measures on burn pathology. Mouse (femoral) bone marrow cells were collected at different intervals after a fullthickness, 25 per cent scald burn. The cells were labelled with tritiated thymidine (SH-TdR) in vitro. The total radioactivity incorporated in the cells was then measured; in the earlier works autoradiographic analyses were also made. It occurred that granulocyte production was strongly depressed at the early post-burn period and part of the mature granulocytes in the bone marrow was even destroyed (Asko-Seljavaara, 1974a). Serum collected at the same post-burn period inhibited intact bone marrow cells in the culture (Asko-Seljavaara, 1974b). We could also confirm the findings of other investigators (Eurenius and Brouse, 1973) that a massive release of mature granulocytes occurs from the bone marrow (Fig. 1) (Asko-Seljavaara, 1974a). When a release of the large granulocyte storage pool is combined with an inhibition of granulocyte production, the bone marrow becomes exhausted at the end of the first week post-burn. The released granulocytes may also produce additional I I M A R R O W BLOOD T I S S U E S i J t [ I I GRANULOPOIESIS MATURATION ] [ [

Volume and fluid replacement in the early post-burn period: an animal experimental study

FOR several years we have performed our experimental burn studies by scalding young domestic pigs (Ahnefeld and Haug, 1976). The pig can be well compared to humans in respect of blood circulation, chemical reactions and skin quality (Kolb, 1967). Furthermore, it is possible to take blood samples of suflicient number and volume for determining the various physical and chemical parameters. We wished to produce major burns and we adopted scalding in order to induce burn shock. From our investigations we discovered that this experimental burn shock represents factors known to occur in human burn shock (Ahnefeld and Haug, 1974).

Peripheral blood T and B lymphocytes in patients with burns. II. Sequential rosette analyses considering burn severity and pseudomonas sepsis

Lymphocytes have been enumerated by E rosette assay for T lymphocytes and by EA and EAC rosette assay for B lymphocytes in 49 burn patients sequentially for 30 days following thermal injury. Severity of burn was used as a classification in a separate analysis of patients. Significant depressions in T lymphocyte percentages and counts per mm 3 were seen in the early post-burn period, the magnitude of which increased with increasing severity of burn. There was a trend towards elevated levels of EAC rosetting cells in mild to moderate injury but there was an absolute depression in severe injury. Extreme depressions of T lymphocytes have been consistently seen in patients who coincidentally developed clinically evident pseudomonas sepsis.

T Lymphocyte Rosette Formation After Major Burns

The ability of lymphocytes to form rosettes with sheep erythrocytes was studied in the acute burn period to quantitate T lymphocytes. Seventeen adult patients with burns of greater than 15% body surface area were studied serially and compared to normal controls. The absolute number of total rosette-forming cells (RFC) averaged 1,229.1 +/- 92.8/cu mm (SEM) for controls. In patients, a comspicuous decrease in absolute number of total RFC occurred at days 3 to 5 postburn (578.0 +/- 144.2/cu mm) (P less than .001) and during days 6 to 10 (799.8 +/- 106.1/cu mm) (P less than .01). Similarly, the percentage total RFC in patients at days 6 to 10 (48.9% +/- 3.3%) was significantly lower than controls (73.9% +/- 0.7%) (P less than .01). The decrease in total RFC did not correlate with the total lymphocyte count or the cortisol level. These findings suggest that T lymphocytes are decreased or have altered rosette-forming ability in the early postburn period and are in accordance with other reports of impaired cellular immunity following burns.

The effect of early excision on bone-marrow cell growth in burned mice

Tritiated thymidine was used in vitro to study mouse bone-marrow cell proliferation at different intervals after severe burn injury. As observed before, strong inhibition was seen in bone-marrow cell production in the early post-burn period, which impairs host resistance to infections. When the wound area was excised early, the inhibition in bone-marrow cell production was totally eliminated. When the excision was made 2–4 hours post burn 3 H-TdR incorporation into the bone-marrow cells was even significantly increased. It is suggested that early removal of necrotic tissue can reduce deleterious antigenic materials and hence decrease general cell destruction and growth inhibition in the burned organism.

Metabolic and nutritional aspects of thermal injury

A MARKEDLY elevated resting metabolic expenditure, as measured by increased oxygen consumption, following major thermal or soft-tissue injury, was first noted in I953 by Cope and his associates. These and other investigators (Gubler and Zimina, 1963; Roe et al., 1965; Roe and Kinney, 1965; Gump et ai., I970) have repeatedly documented the presence of this hypermetabolic response even though thyroid function remains normal and the presence of other known hyperdynamic disease states, such as pregnancy, Paget's disease and cirrhosis, is excluded. Resting metabolic rates of I50-200 per cent of normal have been measured following major thermal injury, and they persist at this elevated level for 2-8 weeks until wound coverage is accomplished. Total caloric expenditures of 5000 kcal/day have been measured during the early post-burn period, by both direct and indirect calorimetry, in extensively burned patients. The hypermetabolism exhibited by burned or traumatized patients is in marked contrast to the hypometabolic rates observed in other semistarvation states. Benedict'sclassicstudies in 1915 revealed a prompt reduction in oxygen consumption to 80 per cent of normal when body-weight had fallen by 10 per cent during starvation. In traumatized patients metabolic expenditure promptly rises despite weight losses of much greater magnitude. It is now well recognized that weight loss in traumatized individuals results from increased gluconeogenesis with striking losses of muscle protein (Cahill, 1970a, b). The non-traumatized starving patient quickly adapts after several days to the utilization

INTRARENAL REDISTRIBUTION OF BLOOD FLOW IN THE EARLY POSTBURN PERIOD

We interpret the findings of the present study and other studies reported here to indicate that alterations of renal outer to inner cortical blood flow distribution develop in the early postburn period. These alterations are similar to those observed by other investigators in animals subjected to various other traumatic events. Such flow redistributions were observed in both untreated animals and those receiving intravenous fluid resuscitation. Sharp reductions in urinary chloride and sodium concentrations observed in conjunction with these blood flow shifts may be a reflection of the relatively greater perfusion of juxtamedullary nephrons, which are alleged to have greater salt-retaining characteristics than their outer cortical counterparts.