Several authors have described long-term clinical effects of smoke inhalation injury [17
]. Fogarty et al. showed ventilatory defect and small airway obstruction were present in 11 survivors of the King’s Cross underground station fire after 6 months [19
]. Desai et al. reported that 64% of pediatric patients (mean burn size of 44% total body surface) with inhalation injury had abnormal spirometry and lung volumes at rest 2 years post-injury [20
]. Park et al. demonstrated the long-term effects of smoke inhalation, by examining airway responsiveness, airway inflammation, and systemic effects, and concluded that inflammatory reaction in the airways and peripheral blood continues for at least 6 months after smoke inhalation [21
]. However, there are no studies using the same criteria that grade simultaneously the degree of smoke inhalation and the same methodology to evaluate lung function. Palmieri suggests the first step in determining the effects of smoke on long-term pulmonary function is to evaluate it in an animal model [22
]. Many animal models with smoke inhalation and cutaneous burn have been described in the literature involving rodents without early excision [1
], but there have been no clinically relevant large-animal models which could monitor pulmonary function and hemodynamics for over and extended period of 2 weeks or more.
Darling et al. demonstrated the high mortality from inhalation injuries is most significant in burns >15% TBSA [25
]. Suzuki et al. also reported that the mean full thickness burn size of 1690 patients with inhalation injury was 20.4% TBSA in Tokyo [26
]. In our model, the size of cutaneous burn was determined in consideration of the effects on pulmonary function. It is well established that inhalation injury increases the mortality in burn patients, but there are few studies to determine whether early excision at 24 h post-injury would aggravate pulmonary function in inhalation injury [6
The present study suggests that early excision and skin autografting do not aggravate pulmonary function in PaO2/FiO2 ratio, Qs/Qt, PAP and PVRI compared with no excision group. At 3 weeks post-injury, these indices showed recovery from lung injury. Excision therapy and autografting were safely performed in sheep with impaired lung function and long-term model of smoke inhalation injury and cutaneous burn without wound infection. In the present model, a cotton smoke insufflation injury (36 breaths) combined with a 20% TBSA third-degree cutaneous flame burn produces a predictable (PaO2/FiO2 < 300) model of acute lung injury (ALI). One of the long-term effects of smoke inhalation injury was demonstrated in lung wet-to-dry weight ratio, an index of pulmonary edema, in the Early Excision group (). To show the long-term effects clearly, further studies are needed using the measurement of collagen deposits, lung compliance and diffusion capacity tests.
There are several wound models in swine for burn treatment [14
]. Unfortunately, it is difficult to maintain tight dressing within the first 4–6 days and keep wound clean without dressing after first dressing change on an awake pig [14
]. In contrast, in the ovine model it is easy not only to measure pulmonary and hemodynamic function, but also to treat and observe the wound as the animals can be maintained in an upright position. In the present model, burn wound of approximately 1900 cm2
could be monitored for 3 weeks without infection. Porcine skin is more similar to human skin than that of sheep [32
], as both porcine and human have sparse body hair and hair follicles play an important role in reepithelialization. However, we speculate that the differences in skin do not have effects on wound healing in our model because wound excision was carried out to muscular fascia and split-thickness skin (20/1000 in. or 0.5 mm) was harvested for grafting. The present burn and smoke inhalation model with early excision is clinically relevant and, to our knowledge, is the first in the world to be used for long-term studies.
Many clinical studies have reported that early excision of the burn wound decreased operative blood loss, reduced the length of hospitalization and incidence of infection [7
]. In the present study, hemoglobin of % baseline and hematocrit of % baseline did not decrease to a statistically significant degree in the early postoperative period, and the average of WHA (mean ± SD) was over 70% at 18 days post-injury. In the Early Excision group, the animals demonstrated no incidence of infection and could have been discharged from hospital had they been patients. In the Control group, two out of six animals (33%) had abscess in lung at 3 weeks post-injury.
At the same time, some differences were exposed between Early Excision and Control groups. In the net fluid balance, early excision and skin grafting statistically increased fluid requirements compared to the Control and the Sham groups (). In the Control group, the urine volume was statistically increased in the refilling period (), and less fluid volume was required compared to the Early Excision in the second 48 h post-injury (). Hypoproteinemia and statistical lower oncotic pressure were found after operation and recovered from 1 week post-injury in the Early Excision group (). These results showed that we have to know the differences between burn/inhalation injury with early excision and burn/inhalation injury alone to determine the fluid resuscitation volume. Progressive anemia, which was measured as Hb and Hct, had appeared in the Early Excision group throughout the experiments though frank bleeding was not observed after surgery (). In a clinical setting, hospitalized burn patients often become anemic because of hemodilution, relative bone marrow suppression, and frequent laboratory draws [33
]. Early eschar excision traditionally has been associated with significant operative blood loss [34
]. Our current findings suggest that supplement of albumin and late blood transfusion should be considered in extensive burn patients after early excision and grafting. Early wound excision had been shown in small-animal study to increase pulmonary leukosequestration compared with the burn injury alone [35
]. In the present model, neutrophil counts statistically significantly decreased compared to Control group and baseline value after burn wound excision. We speculate that neutrophil counts were decreased because of leukosequestration. Xiao-Wu et al. showed that some patients have postoperative pulmonary complications that may counter any benefits from immediate excision such that the 2 effects cancel each other [6