Beneficial effects of a hypertonic solution for resuscitation in the presence of acute hemorrhage.

Crystalloid solutions such as Ringer's lactate have become the standard for initial volume replacement after hemorrhage. Although the relative merits of blood, colloid, and crystalloid have been extensively studied, little attention has been directed toward determining the optimal composition of the crystalloid solution. Based on the beneficial properties of hypertonic lactated saline solution in burn resuscitation, we have extended its use to acute hemorrhage. Using an awake canine model analogous to the clinical situation, we compared hypertonic lactated saline solution with Ringer's lactate solution for resuscitation in the presence of acute blood loss. The hypertonic lactated saline solution group required less fluid to restore and maintain cardiac output and blood pressure while maintaining better urine output. Although the Ringer's lactate solution group had increased shunt function indicative of pulmonary dysfunction, the shunt function in the hypertonic lactated saline solution group did not differ from that in the control group. Serum sodium and osmolality values were higher in the hypertonic lactated saline solution group, but at no time did they approach toxic levels.

Effect of adrenal medullectomy on responses in heat production, plasma catecholamines and body temperature of burned rats to changes in the temperature of the hypothalamus.

Burn (B) and control (C) rats with and without adrenal medullectomy (Adx) 9-11 days postburn underwent warning and cooling of the preoptic anterior hypothalamus (POAH) during calorimetry at 22 degrees and 28 degrees C ambient. Blood was drawn for catecholamine assay during each displacement of the POAH temperature (Thy). The heat production (Hp) for the AdxB group at 22 degrees and 28 degrees C was not different from the Hp for the sham AdxB group (80 +/- 4 vs 86 +/- 8 at 22 degrees C, 58 +/- 8 vs 64 +/- 7 W/m2 at 28 degrees C) in spite of there being no detectable circulating epinephrine (E) for the AdxB groups. Cooling of the POAH of the AdxB 22 degrees C group, however, did not induce a further increment in Hp, in contrast to all other groups. Thy demonstrated good significant negative linear correlation with Hp for all groups. The resulting slopes were not significantly different from one another, indicating no difference in thermal sensitivity of the POAH between the groups. In four of eight groups plasma norepinephrine (NE) demonstrated positive correlation with Hp and in five of eight groups negative correlation with Thy, Plasma E values did not correlate with Hp and demonstrated negative correlation with Thy in two of four possible groups. These data show that postburn hypermetabolism is not dependent on E in the rat and suggest that NE may be calorigenic in burned rats.

Effect of alpha adrenergic blockade on thermoregulation in adrenal demedullated burned rats.

This study in burned rats studied at two ambient temperatures (22 degrees and 28 degrees C) and housed at 28 degrees C was designed to investigate the role of catecholamines in the maintenance of thermal homeostasis following burn injury. Two weeks prior to burn or sham burn, animals underwent adrenal medullectomy or sham adrenal medullectomy. Between postburn days 9 and 13, simultaneous direct and indirect calorimetry was performed following administration of 2mg/kg of phentolamine (alpha adrenergic blocking agent) via a carotid arterial line. Following administration of phentolamine, heat production and body temperature decreased and heat loss increased immediately. The cooling slopes for the burn groups were significantly steeper than for the control groups, within ambient temperatures. Within ambient temperatures, the presence or absence of the adrenal medulla had no discernible effect on the cooling slope of the burns or the controls. The burned animals cooled 1.9-3.5 times faster at 22 degrees than at 28 degrees C, and controls cooled 2.0-3.9 times faster at 22 degrees than at 28 degrees C. Phentolamine produced a several-fold increase in serum concentrations of both norephinephrine (NE) and epinephrine (E), indicating a gross overlap in alpha and beta adrenergic receptor utilization for E and NE. The progressive cooling of the adrenal demedullated burn group at 22 degrees C following phentolamine administration seems to indicate that norepinephrine is calorigenic for rats under these experimental circumstances. These experimental results indicate a relatively non-essential role for catecholamines in the maintenance of thermal homeostasis within the thermal neutral zone in the rat.

The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats.

This study investigates the hypothesis that indomethacin's ability to prevent "fever" following burn injury in rats is mediated via decreased plasma concentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing indomethacin placed in the peritoneal cavity. Seven days later full thickness scald burns to 50% of the body surface area were produced. Following burn injuries, daily blood samples were obtained from a carotid catheter for assay of lipopolysaccharide (LPS), interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body temperature (T(B)) and activity index were obtained every five minutes by telemetry. There were four experimental groups: burn + indomethacin (B-In); burn + polyethylene glycol (Peg) (B-Peg); control + indomethacin (C-In); and control + Peg (C-Peg). Burned animals demonstrated a significant two-fold increase in plasma IL-1alpha levels (p=0.004) and a seven-fold increment in IL-6 (p=0.0001) through the 7th PBD, and indomethacin administration had no significant effect upon the cytokine plasma levels. There were no significant increases in IL-1beta, TNF-alpha or LPS in any group. Indomethacin eliminated the chronic increase in T(B) following burn injury, and this effect was not produced by changes in plasma levels of the endogenous pyrogens IL-1alpha and IL-6.

Vagotomy modifies but does not eliminate the increase in body temperature following burn injury in rats.

INTRODUCTION: Rats with burn injury to > or = 50% of the BSA demonstrate a significant increase in body temperature (T(B)) during light hours, and decrease of circadian variation in T(B). This study investigated the hypothesis that part or all of the signal for increased T(B) in rats with burn injury is transmitted to the central nervous system by way of afferent vagal fibers. METHODS: Four groups of animals were studied: Burn-Sham Vagotomy; Control-Sham Vagotomy; Burn-Vagotomy and Control-Vagotomy. Anesthetized animals had bilateral subdiaphragmatic vagotomy (VagX) or sham VagX performed, and AM radio transmitters were implanted in the peritoneal cavity for the purpose of recording T(B) and activity index (AI). Following a one week recovery period, burn animals received scald burns equal to 50.3 +/- 2.5% BSA. RESULTS: The main effect of VagX upon T(B) was a small but significant reduction in T(B) during dark hours. At least 87% of this decrease in post-burn T(B) was also present for the control vagotomy group. Vagotomy had no effect on the increase in T(B) for the burn groups during light hours. During dark hours, VagX significantly reduced T(B) in burns and controls, and burn injury significantly reduced activity. CONCLUSIONS: One may speculate that afferent vagal signals are partially responsible for maintenance of T(B), with or without burn injury, and that the major signal for increase in T(B) for animals with burn injury is not a neural one via afferent vagal pathways.

Retrospective evaluation of admission criteria for paediatric electrical injuries.

In the medical community, the practice of admitting all electrical burns for 24-48 h of observation, monitoring and laboratory evaluation is widespread. This retrospective review of paediatric electrical burns was conducted to determine which patients may safely be treated as outpatients. Retrospective analysis of all paediatric burns admitted between 1980 and 1991 identified 35 patients with electrical injuries. Patients were divided into two groups for analysis: those burned by exposure to household voltages (120-240 V; n = 26) and those exposed to high voltages, in excess of 1000 V (n = 9). The majority of household electrical injuries occurred secondary to contact with the household 120 V (21/26). Contact with an extremity accounted for the largest number of these injuries (18/26). The mouth was the second most frequent site of injury (7/26). Most of these patients (20/26) had < 1 per cent BSA burn. No patient in the household-voltage group had an arrythmia that required treatment, nor were there any identified examples of compartment syndrome or other vascular complications. Seven patients did require minimal skin grafting. No deaths occurred in either group. The patients in the household-voltage group were significantly younger. High-voltage electrical injuries occurred in an older patient population and required more aggressive care and surgical intervention. This was evident at the time of initial evaluation. Based on these data, healthy children with small partial-thickness electrical burns and no initial evidence of cardiac or neurovascular injury do not appear to need hospital admission.

The interrelationships between wound management, thermal stress, energy metabolism, and temperature profiles of patients with burns.

This prospective randomized study was performed to evaluate the metabolic and thermal responsiveness of patients with burns to thermal stress with three protocols of wound care: group I (n = 7) treated with dressings and variable ambient temperature selected for patients subjective comfort; group II (n = 7) treated without dressings and variable ambient temperature for patient comfort; group III (n = 6) treated without dressings and ambient temperature of 25 degrees C, electromagnetic heaters were set to achieve patient subjective comfort; and group IV (n = 6) healthy volunteers. After baseline partitional calorimetry was performed, individual patients were cold-challenged while subjectively comfortable by sequentially lowering either the ambient temperature or the output from the electromagnetic heaters. Heat balance and temperatures were obtained after each perturbation in external energy support. For patients in groups I and II, subjective perception of thermal comfort (warm, neutral, neutral and fed, cool, or cold) was more strongly correlated (p < 0.02) with the changes in the rate of heat production than the actual ambient temperature. For patients treated with electromagnetic heaters, changes in heat production were most strongly correlated with the energy output from the electromagnetic heaters. Even though the environmental conditions required to achieve a particular level of comfort are quite different between treatment groups, the difference in temperature between the patient's surface and ambient is approximately the same for groups I, II, and IV for each subjective state.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential excision and grafting of the burn injuries of 1507 patients treated between 1967 and 1986: end results and the determinants of death.

The development of a more aggressive approach to burn wound management, leading to complete excision within 72 hours after burn, has led some to conclude that total early excision is a major force behind improved survival rates. We have summarized the results of treatment of 1507 patients with burn injuries treated between 1967 and 1986. Wounds were managed with use of standard topical therapy, occlusive dressings, and staged excision and grafting of full-thickness injury or deep dermal injury (not healed by 21 days). Data were analyzed with use of a logistic-regression model because, with the exception of older patient cohorts, the data did not fit the probit model. The major determinants predicting death were the percentage of body surface area burned, age, smoke inhalation, and the percentage of full-thickness burn. Concordance was 97%. These data show that aggressive sequential wound excision and grafting produces end results comparable with those achieved with complete early burn wound excision for similar age ranges and injury. Early harvest of available donor sites in patients with large burns may be more important to survival than complete early wound excision.

The effect of wound management on the interaction of burn size, heat production, and rectal temperature.

Metabolic and temperature data were collected for 56 patients with burns managed with four wound care protocols. Group I (n = 7) treated with dressings and variable ambient temperature selected for patient subjective comfort; group II (n = 7) managed without dressings and variable ambient temperature for patient comfort; group III (n = 6) no dressings, ambient temperature of 25 degrees C and the output of electromagnetic heaters adjusted for patient comfort; group IV (n = 36) dressings and ambient temperature of 28 degrees C. All groups were cold challenged: groups I and II by sequentially lowering ambient temperature, group III by decreasing the electromagnetic heater output, and group IV by removing dressings with ambient temperature remaining at 28 degrees C. Only groups II and IV demonstrated correlation between percent body surface area burn and heat production. The slope of the regression for group IV neutral was significantly less than that for group IV cold and group II neutral and cold. The relationship between percent body surface area burn and rectal temperature for groups I, II, and III neutral was equal to .03 degrees C increase in rectal temperature per 1% body surface area burn (Y = 37 + 0.03; r = 0.74; df 18; p < 0.01) and was not significantly different when cold. This predicts a 1.5 degrees C increase in rectal temperature for a patient with a 50% body surface area burn who does not have sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy balance studies and plasma catecholamine values for patients with healed burns.

We report heat balance studies and plasma catecholamine values for 49 children and young adults with healed burn wounds (age range 0.6 to 31 years and burn range 1% to 82% body surface area burned; mean 41%). All measurements were made during the week of discharge. Heat production for patients with healed burns was not significantly different from predicted normal values. However, compartmented heat loss demonstrated a persistent increment in evaporative heat loss that was secondary to continued elevation of cutaneous water vapor loss immediately after wound closure. A reciprocal decrement in dry heat loss was demonstrated (as a result of a cooler average surface temperature, 0.84 degree C cooler than the average integrated skin temperature of five normal volunteers who were studied in our unit under similar environmental conditions). Mean values for plasma catecholamines were in the normal range: epinephrine = 56 +/- 37 pg/ml, norepinephrine = 385 +/- 220 pg/ml, and dopamine = 34 +/- 29 pg/ml. In conclusion, patients with freshly healed burn wounds have normal rates of heat production; however, there is a residual increment in transcutaneous water vapor loss, which produces surface cooling and decreased average surface temperature, which in turn lowers dry heat loss by an approximately equivalent amount.

Relationships between heat production, heat loss, and body temperature for rats with burn injuries between 26% and 63% of the body surface area.

Burn injury in man is characterized by increased body temperature proportional to burn wound size and may represent fever and/or hyperthermia. A nonseptic animal model used to study this phenomena has not been described. To test the hypothesis that large burn injuries in rats would produce increased body temperature, the rectal, skin, and body temperatures were sequentially measured and were calculated for rats in the control group and rats with burn injuries covering 26% to 63% of the body surface area [< or = 35%, 36% to 45%, and > or = 46% body surface area]. The group with burns covering > or = 46% of the body surface area had significantly higher rectal temperatures than did at least one other group on postburn days 7, 9, 11, 13, 18, and 20. On postburn days 7 and 11 this increase was significantly higher than that of all burn and control groups. Animals did not demonstrate any overt evidence of wound infection. These data do not establish a cause for increased body temperature after burn injury but suggest that a reproducible animal model may be possible for the study of the cause of increased body temperature after burn injury.

Guinea pigs with large burns are consistently hypermetabolic without an associated increment in rectal temperature.

This study was conducted to examine the guinea pig as a suitable model for the study of the postburn hypermetabolic response and the febrile response that accompanies burn injury in man. Thirty animals were randomly assigned to four groups: > 50% body surface area burn (n = 6); 45% to 50% body surface area burn (n = 10); < 45% body surface area burn (n = 6); and controls (n = 8). On postburn days 3, 7, 11, 13, and 15, sequential temperature measurements were made. On postburn days 7 to 15, the randomly selected burn group (n = 12) and the control group (n = 8) had calorimetry studies performed. Sequential rectal temperature data demonstrate that the guinea pig does not mount a prolonged or consistent febrile response after burn injury (p > 0.05 for burn group vs control group on postburn days 7 to 13; p < 0.05 for postburn days 3 and 15 only). However, the burned guinea pig is significantly hypermetabolic after burn injury, with significant increases in dry and evaporative heat loss. The hypermetabolic response was proportional to burn wound size. Guinea pigs are not an ideal model for the study of the postburn febrile response; however, this is an excellent model for the study of postburn hypermetabolism.

Polyclonal antibodies to rat interleukin-6 attenuate fever in rats after burn injuries: a preliminary report.

Rats with 50% total body surface area full-thickness burn injuries have sustained increases in body temperature without evidence of sepsis. In this animal model, the only known endogenous pyrogen consistently present in plasma is interleukin-6 (IL-6). We investigated the hypothesis that IL-6 acts as an endogenous pyrogen and produces the observed increase in body temperature. Body temperature and activity index were recorded every 5 minutes for control rats and rats with burns (50% total body surface area scald burns) for a period before the burn injuries and through the eighth day after the burn injuries. On the fifth day after the burn injuries, between 8 and 9 AM, control animals and animals with burns were given an intra-arterial dose of IL-6 polyclonal neutralizing antibody (IL-6 pAb) that was equivalent to one half of the neutralizing dose of IL-6 pAb. This calculation was based on plasma levels of IL-6 obtained from rats with burns in previous studies and on the neutralizing capability of the IL-6 used. On the sixth and seventh days after the burn injuries, a full neutralizing dose of IL-6 pAb was given. Blood samples were obtained for IL-6 assays at baseline and after treatment with IL-6 pAb but were lost because of the failure of an ultracold freezer. A one half neutralizing dose of IL-6 pAb produced no discernible effect on the body temperature of the control animals or of the animals with burns. On the sixth and seventh days after the burn injury, IL-6 pAb produced 45% and 34% respective decreases in body temperature compared with the animals with burns that received saline solution (P < .05 for both comparisons). On the eighth day after the burn injuries, the effect had completely dissipated. We concluded that our results support the idea that increased circulating levels of IL-6 may be causally related to fever that occurs in nonseptic rats with large burn wounds.

The response in heat production, plasma catecholamines, and body temperature of burned rats to hypothalamic temperature displacement.

Rats, with the preoptic anterior hypothalamus implanted with two thermodes and a thermocouple reentry tube, had simultaneous direct and indirect calorimetry performed [during the ninth to eleventh postburn day interval] at ambient temperatures of 22 degrees and 28 degrees C. During calorimetry, blood was drawn at baseline and near the end of each period of displacement of the preoptic anterior hypothalamus temperature for catecholamine assay. Cooling the preoptic anterior hypothalamus resulted in a significant increase in heat production and plasma epinephrine and norepinephrine concentrations for both burn and control groups at 22 degrees C and 28 degrees C (p < 0.05 for all comparisons). Heat production demonstrated consistent negative linear correlation with preoptic anterior hypothalamic temperature. Plasma epinephrine values correlated with preoptic anterior hypothalamic temperature for only the controls at 28 degrees C ambient, whereas norepinephrine had significant linear correlation with heat production for all groups and significant negative linear correlation with preoptic anterior hypothalamic temperature. These data indicate norepinephrine may be more important than epinephrine in the maintenance of postburn hypermetabolism in this rat burn model while demonstrating that the hypermetabolism is appropriately responsive to perturbation of preoptic anterior hypothalamic temperature.

Pathogenesis of fever in a rat burn model: the role of cytokines and lipopolysaccharide.

We investigated the possible causal relationship between interleukin-6 (IL-6) and increased body temperature (T(B)) in a rat burn model. Transmitters for measuring core temperature and estimating activity were implanted in the abdominal cavity. Animals in the burn group were clipped and received full-thickness scald burns to 45% to 55% of the body surface area, and control animals were clipped. T(B) and activity were measured continuously through the tenth postburn day. Carotid lines were placed, and serial blood samples obtained for lipopolysaccharide, IL-6, and tumor necrosis factor-alpha assay. From the third through the tenth postburn day, the burn group had a consistently significantly higher T(B) during light hours than the control group did (average, 0.45 degrees C +/- 10 degrees C, p = 0.0001). Differences in activity during light hours were not significant between the two groups, therefore, do not account for the observed significant difference in T(B). The average IL-6 serum levels were 3.5-fold higher for the burned animals. In this study, burn and control serum levels of IL-6 demonstrated positive correlation with T(B). These data suggest, but do not prove, a causal relationship between IL-6 and fever in the rat burn model, and make it unlikely that circulating systemic lipopolysaccharide is the cause.

Chronic indomethacin administration blocks increased body temperature after burn injury in rats.

This study investigates the hypothesis that continuous administration of indomethacin (a cyclo-oxygenase inhibitor) will chronically reduce body temperature (TB) in burned rats (i.e., modulate "true" fever). Male Sprague-Dawley rats had radio transmitters and osmotic pumps (containing indomethacin) placed in the peritoneal cavity, and 7 days later large full-thickness scald burns were produced. Activity and TB were continually recorded through the 14th postburn day (PBD). There were 4 experimental groups: burn + indomethacin (B-In), n = 9; burn + polyethylene glycol (B-Peg), n = 6; control + indomethacin (C-In), n = 9; and control + polyethylene glycol (C-Peg), n = 6. From PBD 5 through PBD 10, the B-Peg group had consistently and significantly higher TB during light hours than the B-In, C-In, and C-Peg groups. From PBD 7 through PBD 12, the B-In group had an average TB during light hours significantly lower or not different than the C-In and C-Peg groups. These results support the hypothesis that in this burned-rat model chronically increased TB during the light hours may be "fever" (rather than hyperthermia) and that the final effector link could be a prostanoid because changes in activity do not explain the changes in body temperature.

Calorigenic response of burned rats with adrenal medullectomies to catecholamines.

In previous studies, we established that circulating epinephrine (E) is not essential for a normal hypermetabolic response to burn injury in the rat, within the zone of thermal neutrality. In other studies, burned rats with adrenal medullectomy (AdxB) studied at 22 degrees C were unable to maintain rectal temperature (TR) after alpha-adrenergic blockage. These data suggest that norepinephrine (NE) is calorigenic in such animals without formal cold acclimation. These studies investigate the hypothesis that, contrary to the usual belief, norepinephrine might be calorigenic in rats without formal cold acclimation. Burned (B) and control (C) rats with adrenal medullectomies (Adx) and Sham (S) Adx (AdxB, SAdxB, AdxC, and SAdxC) were housed at either 22 degrees C or 28 degrees C. Calorimetry was performed during the eighth to eleventh days after the burn. For groups housed at 22 degrees C and studied at 28 degrees C, NE given intravenously (iv) produced an average 16.5%+/-3.3% increment in heat production (HP) for the four groups, which was significant for AdxB, SAdxB, and SAdxC. Intravenous administration of E produced an average increment in HP of 4.44%+/-4.1%, which was not significant. HP was significantly higher after NE than E in three cases. Studies with animals housed at 28 degrees C and studied at 28 degrees C produced intermediate but similar results. For groups housed at 28 degrees C and studied at 22 degrees C, iv administration of E and NE produced average decreases in He of 18%+/-6.7% for E and 10.75%+/-4.7% for NE. Except for the AdxC group, these differences were significant. These data suggest that chronic exposure to an ambient temperature of 22 degrees C produces an enhanced calorigenic response to NE in burn and control rats. Based on the data presented here, combined with earlier studies, NE must be considered as a facilitator for hypermetabolic response to burn injury in the rat. It is interesting to speculate whether NE is calorigenic for patients with large burn wounds, which are managed without dressings at ambient temperatures below thermal neutrality.

Absence of postburn hypermetabolism in a group of children with serious burns.

Hypermetabolism proportional to wound size is the expected response in patients who sustain large burns. This metabolic response persists until wound closure is achieved. The value of this response to the injured host remains unproven. Between 1978 and 1991, 104 patients with burns covering 30% or more of the body surface area underwent partitional calorimetry as a component of various research protocols. Thirteen of these patients failed to demonstrate an increase in metabolic rate as compared with a control group. These patients without hypermetabolism were compared with case-matched patients who demonstrated the expected increase in metabolic rate. Although they were not hypermetabolic in response to the burn injury, five of these patients were exposed to a cold stress and were able to increase their metabolic rate appropriately. The failure to mount a hypermetabolic response did not impact the clinical course as measured by survival, length of hospital stay, or maximum weight loss.

Alteration in temperature regulation induced by burn injury in the rat.

The preoptic anterior hypothalamus (POAH) of rats housed at three ambient temperatures was implanted with perfusion apparatuses. Response of heat production to displacement of POAH temperature was determined for control animals and animals with burns (31% +/- 3% total body surface area). At an ambient temperature of 22 degrees C there was a significant increase in thermosensitivity of the POAH for both control rats and rats with burns compared with thermosensitivity at 32 degrees C. Within ambient temperatures there was no effect on thermosensitivity detected for rats with burns compared with control rats. The threshold temperature for heat production was shifted significantly upward (p less than 0.05) both by a lower ambient temperature and by burn injury. The reference temperature for heat production was also shifted to the right by burn injury (p less than 0.05). The significant shifts to the right for threshold temperature and reference temperature for heat production enhance the organisms's ability to meet the stress of the hypermetabolic response. At a warm ambient temperature (32 degrees C) there are no significant differences in thermoregulation detected in animals with burns or control animals.

The effect of ablation of the preoptic anterior hypothalamus on energy metabolism and plasma catecholamines after burn injury in the rat.

Rats with burn injuries demonstrate changes in thermoregulation including an upward shift of the set-point and reference temperatures with no change in sensitivity of the response in heat production to displacement of the temperature of the preoptic anterior hypothalamus. In the present studies, the response in plasma and urinary catecholamines to burn injury after destruction of the preoptic anterior hypothalamus was examined in the rat. Preoptic anterior hypothalamic lesioning impaired the hypermetabolic response to burn injury, and at 22 degrees C, burned lesioned rats were hypothermic. Furthermore, plasma levels and urinary excretion rates for catecholamines were not decreased in burned lesioned rats, but rather showed an inverse relationship with heat production. Burned lesioned rats were capable of maintaining body temperature at an ambient temperature of 28 degrees C. This suggests that a less precise thermoregulation is present in lesioned animals. Rats in which the preoptic anterior hypothalamus has been destroyed have reduced tolerance to burn injury.