Postburn Period Research Articles

Early Mortality and Temperature Regulation in Burned Mice following Administration of Catecholamines and Adrenergic Receptor Blocking Drugs

The effect of catecholamines and adrenergic receptor blocking drugs on mortality and body temperature was studied in mice subjected to burn, tourniquet, and endotoxin shock at an environmental temperature of 25 degrees C. Epinephrine and norepinephrine (0.5 mg/kg) injected intraperitoneally postburn increased shock mortality significantly (p less than 0.05); pretreatment with these catecholamines had no effect. Pretreatment of burn- and tourniquet-traumatized mice with propranolol (25 mg/kg) significantly decreased shock mortality, while pretreatment with dibenamine (25 mg/kg) significantly lowered early mortality after endotoxin. None of the catecholamines or their blocking drugs significantly prevented the characteristic immediate fall in core temperature after the three types of shock. At 6 days postburn, however, a combination of propranolol and dibenamine caused a marked fall in core temperature (p less than 0.05). These results indicate that beta-catecholamine agonists could play an important role in acute burn mortality and that both alpha- and beta-catecholamine agonists could significantly influence body temperature regulation and metabolic rate during the late postburn period.

Late Results Following Treatment of Deep Burns of the Hands

During a 10-year period, 467 patients with burns involving the hands have been treated, 290 of whom during the past 5 years. Two groups of patients were examined: the first were those who had received treatment between 1967 and 1971 using the exposure method and the reconstruction with skin grafts only after the spontaneous separation of the eschars, and the second, using the closed method and early or late excision of the necrotic tissue followed by covering with split-thickness grafts. In this second group are included also those patients whose burns can be classified as medium depth at the time of admission but in whom experience has shown that one is dealing with lesions with a tendency to become deeper during the post-burn period. For these cases a dermabrasion of the lesions was performed without covering with free grafts. In the cases subjected to surgery using the technique of tangential excision and dermabrasion in order to reach the more difficult areas such as the interdigital spaces, dermabrasion was only performed between the 2nd and the 28th day. The removal of the burned tissue was followed by covering with free grafts, except in those cases in which the depth was in doubt. The results obtained have demonstrated that in the first group the scars have led to serious invalidating consequences which have necessitated long and complex surgical reconstruction programmes. In the second group almost complete function has been restored with the aid of only minimal surgical correction, most often in the interdigital spaces. We would like to emphasize the usefulness of surgery in those cases on the borderline between medium and full thickness. The tendency of these lesions to become deeper has often led to scars which are very similar to those following the deep lesions.

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).

Emergency Nursing Care of the Burned Patient

The emergency nursing care of patients with major burns presents one of nursing's greatest challenges. Priority is given to lifesaving measures. After a quick overall assessment, a careful estimate of fluid and electrolyte loss is made. An issue in burn care is whether colloids should be given in the immediate postburn period. Large amounts of fluid are always given, and balanced salt solutions are being used increasingly without colloid. The patient's response to fluid therapy can be monitored by central venous pressure readings, vital signs, and hourly measurements of urinary output. Psychologic and physiologic stress intensify the problems and should be kept to a minimum. Only after other aspects of care have been attended is attention directed to care of the burn wound.

Hyperglucagonemia and hepatic ketogenesis in burned swine.

A porcine burn model demonstrates hypoglycemia in spite of hyperglucagonemia. The ketone response to free fatty acids is defined for the normal and burned pig. Ketogenesis is augmented beyond that expected from free fatty acids during the postburn period. These metabolic changes may be related to the hyperglucagonemia and/or the relative hypoinsulinemia observed in the burned pig.

Morphological changes of lymph nodes of children following acute thermal burns

Summary The morphology of lymph nodes in children following acute thermal burns was correlated with immunological function. Lymph nodes from different parts of the body were obtained from 100 autopsies of burned children, with survival time ranging from 10 hours to 114 days post burn. Marked depletion of thymic-dependent areas was noted; this began early in the post-burn period during the time in which the number of peripheral blood lymphocytes decreased. This change was accompanied by an increase in pyroninophilic cells in the bursal-dependent areas of the nodes. This study revealed that morphological alterations in the lymphoid tissues of burned children were present for as long as 114 days post burn.

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.

Effect of Thermal Trauma on Numbers and Function of T and B Cells from Mouse Spleen

Swiss-Webster female mice were given a moderately severe burn, and studies were carried out on the number and function of T and B cells from the spleens of burned and normal mice. The results showed a significant decrease (p less than 0.05) in the number of T and B cells for 2-3 days after burning with a rapid return to normal and a subsequent rise above normal at 14 and 21 days postburn (p less than 0.05). In the test for function, burned mice had a significant decrease in spontaneous mitotic activity of both T and B cells during the 21-day postburn period. When spleen lymphocytes were incubated with purified mitogens, both T and B cells showed a significantly diminished mitotic response in most of the burned animals.

REDUCTION IN C3 CONVERSION IN PATIENTS WITH SEVERE THERMAL INJURY

Serum opsonic activity for E. coli 075, concentration of native C3 and C3 conversion by inulin were determined in the sera of five patients with burns involving 45% to 80% total body surface during 3 weeks postburn. In all patients, opsonic activity, C3 concentration, and C3 conversion were reduced during the first week following the injury. C3 was restored to normal or elevated levels by the end of the first week postburn and remained normal or elevated thereafter for the duration of the study. In two patients, opsonic activity and C3 conversion were markedly reduced during the entire 3-week postburn period. In the other three patients, opsonic activity was fully restored to normal within 1 week postburn and, in two of these patients, remained normal thereafter for the duration of the study. In the other patient, opsonic activity became reduced again during the third postburn week. C3 conversion in all five patients remained at a low normal or abnormal level during the entire period of study. Addition of normal human serum to the burn sera fully restored opsonic activity to normal but did not normalize C3 conversion. The results suggest that reduced opsonization is related to a deficiency of serum proteins, whereas reduced C3 conversion may be caused by a circulating inhibitor. Both abnormalities were shown to be associated with microbial infections in burned patients.

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.

Fiberoptic bronchoscopy in acute inhalation injury.

Fiberoptic bronchoscopy proved to be a simple, safe, and accurate method of diagnosing acute inhalation injury. Both the anatomic level and the severity of large airway injury were easily identified. The identification of a supraglottic and infraglottic component to inhalation injury was not only helpful in determining the appropriate therapy but also in predicting ultimate pulmonary complications. When bronchoscopy was used in conjunction with the 133Xenon scintiphotoscan, both large and small airway injuries could be identified. The only clinical situation where bronchoscopy failed to identify an inhalation injury was in the immediate postburn period if the patient wasin hypovolemic shock. In this particular clinical circumstance the characteristic mucosal alterations may be absent; yet if bronchoscopy is performed after hypovolemic shock has been corrected, mucosal changes characteristic of inhalation injury will be seen.

Lymphoid Response of the Burn Patient

Clinical observations have long suggested immunologic compromise in burned patients. Resolution of the immune system into cooperative dual components of T-cells mediating delayed hypersensitivity and B-cells mediating antibody responses prompted the present survey of T-cell and B-cell changes after acute thermal burn injury. Adults and children sustaining extensive burn injuries were studied for up to 60 days after injury. T-cell function was assessed by lymphocyte counts, in vitro lymphocyte synthesis of RNA and DNA with and without mitogenic stimulation, and lymphocyte response and stimulatory capacities in the mixed lymphocyte culture (MLC) reaction. B-cell function was studied by quantitation of the major classes of circulating immunoglobulins. Transient lymphocytopenia, increased RNA and DNA synthesis rates by both mitogenstimulated and unstimulated lymphocytes, and impairment of lymphocyte response and stimulation in the MLC were observed early in the postburn period. These parameters tended to normalize by the third week after injury. Immunoglobulin levels, particularly IgG, were depressed significantly the first week postburn, but were normal or elevated by 60 days. These studies document both T-cell and B-cell changes postburn,which appear to be reversible with the recovery phase. A transient shift of circulating lymphocytes toward the B-cell type is suggested and early depression of immunoglobulin levels is notable. Both types of changes likely contribute to the immunologic compromise of the acutely burned patient.

PROGRESSIVE PULMONARY INSUFFICIENCY AND OTHER PULMONARY COMPLICATIONS OF THERMAL INJURY

Progressive pulmonary insufficiency appears to be a universal response to the lung to a variety of injuries which damage the pulmonary-capillary emdothelium. Persistent hyperventilation, unresponsive to the administration of oxygen, is the earliest clinical sign of this complication of trauma and should prompt close monitoring of pulmonary function (measurement of arterial blood gas and pH levels, Vd/Vt A-aDo2, minute ventilation, vital capacity and inspiratory force) to assess the severity of the disease, the need for mechanical ventilatory support and the effectiveness of treatment. Other pulmonary complications of burn injury range from carbon monoxide poisoning and narcotics overdosage in the immediate postburn period through marked hyperventilation directly related to burn size occurring in the absence of significant parenchymal change to later occurring hematogenous and airborne pneumonia. Inhalation injury, a chemical tracheobronchitis which significantly increases the mortality of a given-sized burn, may be present immediately postburn but clinically inapparent for 48-72 hours. 133Xenon lung scans permit early diagnosis of this pulmonary injury and the timely institution of a graduated therapeutic response keyed to the severity of pulmonary disability. Knowledge of the pathogenesis of each of these complications is requisite for the physician caring for burn patients and permits the employment of rational preventive and therapeutic measures.

Histological aspects of burn wound healing

The damage caused by thermal trauma is augmented by the subsequent inflammatory response in a similar fashion to reperfusion injury. Animal studies have demonstrated a significant role for neutrophils in this delayed damage, but little is known about the numbers of neutrophils or other leucocytes that enter human skin following burns. We have longitudinally examined profiles of leucocyte migration into five cases of human partial thickness burns in relation to continued dermal microvascular destruction during the acute post-burn period. All burn wounds had a rapid influx of neutrophils that was followed by a delayed influx of macrophages. Compared to the controls, the two superficial burns also had rapid and sustained influx of CD4 and CD8 lymphocytes via patent post capillary venules in the dermal superficial vascular plexus, whilst in the three deeper burns, in which this superficial vascular plexus was occluded, the number of lymphocytes decreased. These results suggest that the patterns of leucocyte extravasation were dependent on the initial level of vascular occlusion, indicating that the dermal microvascular anatomy plays a pivotal role in determining the composition of the extravascular inflammatory cell infiltrates. The potential importance of this finding is highlighted by the differences in wound behaviour associated with the different leucocyte profiles.

Fluid Volume and Electrolyte Changes of the Early Postburn Period

The fact that over half of all burn deaths still occur within the first 10 days following thermal insult suggests that both the initial resuscitation and the subsequent fluid volume changes and alterations in electrolyte metabolism play significant roles in the high mortality percentage associated with the early postburn period.

Ultrastructural alterations in peripheral blood lymphocyte profiles following acute thermal burns

Acute thermal burns result in impaired cellular immunity. This is reflected by an immediate lymphocytopenia, impaired delayed skin hypersensitivity, decreased allograft rejection potential, depletion of thymic dependent areas of lymphoid tissue, failure of peripheral blood lymphocytes (PBL) to respond to PHA, and a defect in both the response and stimulation capacity of PBL in mixed lymphocyte culture. The present study investigates the ultrastructure of the PBL of patients with acute thermal burns and correlates their morphology with the immunological defects previously shown to be present. Based upon their ultrastructural morphology, the PBL were divided into five cell types: small lymphocytes, large lymphocytes with dispersed ribosomes, large lymphocytes with aggregate ribosomes, large lymphocytes with varying amounts of rough endoplasmic reticulum, and plasma cells. The serial studies performed in 14 adult burn patients were compared with similar studies performed in a group of 15 normal controls. On the first day post-burn, the PBL profile did not differ significantly from that of a normal group of adults although the lymphocyte count in peripheral blood was already decreased. By the second day a significant shift in the morphology of the PBL towards cells having larger quantities of rough endoplasmic reticulum had occurred coincident with a marked fall in the percentage of small lymphocytes present. With the passage of time this change became more pronounced. By 6–10 days post-burn, a mean of more than 30% of the PBL could be identified as either immature or mature plasma cells. Following this time of maximal change a return toward normal was seen, so that by Day 21–23 post-burn, the PBL profile had returned to essentially normal values. A comparison of these studies with other studies performed on patients with acute thermal burns makes it apparent that in the immediate post-burn period a marked defect in cellular immunity or T-cell function occurs simultaneously with a marked stimulation in humoral immunity or B-cell function. The latter abnormality is reflected by the development of a polyclonal gammopathy and the development first of a marked B-lymphocytosis followed by a marked plasmacytosis coincident with the return of PBL counts to normal. The mechanisms causing these changes in the burn patient are not known.