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Effect of inhalation injury, burn size, and age on mortality: a study of 1447 consecutive burn patients.

The relative impact of inhalation injury, burn size, and age on overall outcome following burn injury was examined in 1447 consecutive burn patients over a five and a half year period. The overall mortality for all patients was 9.5% (138 of 1447). The presence of inhalation injury, increasing burn size, and advancing age were all associated with an increased mortality (p < 0.01). The incidence of inhalation injury was 19.6% (284 of 1447) and correlated with increasing percent total body surface area (%TBSA) burn (r = 0.41, p < 0.01) and advancing age (r = 0.15, p < 0.01). The overall mortality for patients with inhalation injury was 31% (88 of 284) compared with 4.3% (50 of 1163) for those without inhalation injury. Using multivariate analysis inhalation injury was found to be an important variable in determining outcome, but the most important factor in predicting mortality was %TBSA burn (accuracy = 92.8%) or a combination of %TBSA burn and patient age (accuracy = 93.0%). Adding inhalation injury only slightly improved the ability to predict mortality (accuracy = 93.3%). The presence of inhalation injury is significantly associated with mortality after thermal injury but adds little to the prediction of mortality using %TBSA and age alone.

Adolescent↗

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults.

BACKGROUND: In the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors. METHODS: We performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05. RESULTS: After adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines. CONCLUSION: Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Adult↗

Survival of severe ARDS with five-organ system failure following burns and inhalation injury in a 15-year-old patient.

OBJECTIVE: To show the effectiveness of an integrated therapeutical approach in a severe case of acute respiratory distress syndrome (ARDS) following burns, inhalation injury with therapy-refractory oxygenation under maximized ventilatory settings, and an overall complicated clinical course. PATIENT AND METHODS: Case report of a patient with severe inhalation injury and burns in an intensive care unit setting, undergoing cardiopulmonary resuscitation (CPR), nitric oxide (NO)-inhalation, surfactant-, kinetic-, and urodilatin-therapy. CASE REPORT: A 15-year-old male presented with deep dermal and full thickness thermal injuries involving 25% of his total body surface area. Shortly after presentation, the patient developed therapy-refractory respiratory failure, cardiac arrest, and subsequently suffered five-organ system failure (lung, heart, gastrointestinal, liver, kidney), in addition to burn injury, and ischemia related cerebral lesions. The patient was successfully treated with cardiac resuscitation, extra corporeal membrane oxygenation (ECMO), NO, kinetic therapy, surfactant, urodilatin, and other standard intensive care regimens. Three months post-trauma the patient was discharged home, nearly fully recovered. CONCLUSIONS: In a patient with severe ARDS, oxygenation failure under maximized ventilatory settings, and subsequent five-organ system failure, an integrated therapeutical approach comprising ECMO, NO, kinetic therapy, surfactant, and urodilatin did cross-bridge respiratory and vital functions, enabling overall survival.

Adolescent↗

The Parkland formula in patients with burns and inhalation injury.

Clinical concern over the fluid status of patients with burns and inhalation injury led us to review the course of 101 consecutive adult patients with large (20%-60% BSA) burns, all resuscitated with the Parkland formula. The results indicate that this regimen may have resulted in unnecessarily large fluid loads in patients with inhalation injury. In order to avoid the highly significant excess amount of fluid over the calculated estimate, patients with burns and inhalation injury should be resuscitated with substantially less than formula predictions, with acceptance of urine output in the range of 0.3-0.5 ml/kg/hr.

Adult↗

Alveolar macrophage chemotaxis in fire victims with smoke inhalation and burns injury.

In vitro migration of alveolar macrophages was studied in 24 fire victims and 19 controls; all subjects were cigarette smokers. Unstimulated (P = 0.01) and stimulated migration towards casein-(P = 0.01) and zymosan-activated serum (P = 0.002) of macrophages from smoke inhalation patients (SI) (n = 19) was increased when compared to control subjects (CS). Migration of alveolar macrophages from patients with burns without smoke inhalation (burns only, BO) was not increased. Patients with smoke inhalation and no burns (smoke only, SO) (n = 9) had increased migration when compared to controls but this was not statistically significant. Patients with smoke inhalation and burns (SB) (n = 10) had increased unstimulated migration (P = 0.01) and increased migration towards casein (P less than 0.005), ZAS (P less than 0.002) and F-met-leu-phe (P less than 0.05) when compared to controls (CS). Lavage fluid from the fire victims displayed chemotactic activity towards normal human neutrophils and its analysis for the components of the complement cascade proved positive (Clq, Clr, Factor B and C3). These data suggest that activation of alveolar macrophages may contribute to the development of pathophysiological changes in patients with smoke inhalation (SI) and particularly those with smoke inhalation and burns (SB).

Burns↗

[Inhalation lesions in the burn patient].

Inhalation injuries are currently the factor most responsible for mortality in thermally injured patients. Inhalation injuries may occur independently, but generally occur together with skin burn. Smoke inhalation affects all levels of the respiratory system and the extent of the inhalation injury depends on the duration, exposure, amount and toxicity of the fume temperature, concentration and solubility of toxic gases, the occurrence of the accident in a closed space and pre-existing diseases. Smoke inhalation also induces changes in the systemic organs with the need for more fluid for resuscitation. Systemic vasoconstriction, with an elevation in systemic vascular resistance, a fall in myocardial contractility and a great increase in lymphatic flow in soft tissue are the most important changes in systemic organs. On admission of a burn patient there is a high suspicion of inhalation injury when there are signs and symptoms such as hoarseness, strides, dyspnea, carbonaceous sputum, anxiety or disorientation, with or without face burns. The patient with these findings has partial airway obstruction and there is substantial risk complete airway obstruction occurring of secondary to the edema. Patients with suspected inhalation injury should be intubated so as to maintain airway patency and avoid a total obstruction. This group of patients frequently develop respiratory failure with the need for mechanical ventilatory support. Nosocomial infections, sepsis and multiple organ system failure may occur. Late complications of inhalation injury are tracheitis, tracheal stenosis or tracheomalacia and chronic airway disease, which is relatively rare. Early diagnosis of inhalation injury and treatment in a Burn Unit by a group of highly motivated clinicians and a good team of nurses is essential in order to decrease the morbidity and mortality related to inhalation injury.

Burns, Inhalation↗

Burns.

Inhalation injuries still significantly increase the morbidity and mortality of burn patients. Advances in ventilatory support appear to decrease the frequency of pneumonia and improve the survival of patients. It is now well accepted that early enteral feeding of patients with burn injuries is very important. The addition of anabolic agents in burn care and nutrition may be of importance. Patients receiving pre-storage filtered blood components have fewer blood transfusion-induced side effects and the requirement for transfusion is reduced. Current research on the cellular response to burn injury holds promise for further improvement in burn care.

Journal Article↗

Serum procalcitonin as an index of inhalation injury in burns.

The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal-region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury-associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients.

Biomarkers↗

Inhalation injury--a major burn complication.

Inhalation injury results from exposure to the toxic gases, chemicals, and particulate matter of smoke to the respiratory tract. New synthetic materials have increased the toxicity of chemicals in smoke and added to the complexity of inhalation injuries. Clinical diagnosis is often difficult, but a high index of suspicion in victims of certain fire situations, coupled with early diagnostic bronchoscopy, will identify most victims. Prior to early bronchoscopy, the mortality rates for the combination of inhalation injury and body surface burn ranged from 75% to 90%. Early diagnosis, expectant management, and meticulous aseptic techniques can decrease the mortality rate to less than 30%.

Burns, Inhalation↗

Influence of demographics and inhalation injury on burn mortality in children.

BACKGROUND: Pulmonary failure has emerged as one of the leading causes of mortality in burned children due, in part, to the success in reducing the incidence of sepsis, early surgery and fluid resuscitation, and new advances in nutritional support. To evaluate the effect of pulmonary injury, age, gender, race, and burn size on mortality, the records of 3179 burned children admitted to our burn center from 1985 to 2001 were reviewed. In this population, 1246 were admitted within 14 days of injury with burns greater than 20% of their total body surface area (TBSA). METHODS: Lethal burn areas (LAs) for a thermal injury only or burn plus inhalation injury were estimated from best fit probit curve within 95% confidence limits. Data analysis was by chi(2)-test, t-test, or Fisher's exact test where appropriate. RESULTS: The lethal burn area for a 10% mortality rate with and without concomitant inhalation injury was a 50 and 73% TBSA burn, respectively. Children up to the age of 3 with >/=20% TBSA burns had a higher rate of mortality (9.9%) compared to those 3-12 years of age (4.9%) and 13-18 years of age (4.2%). Children with 21-80% TBSA burns showed a significant difference in mortality (P<0.05) between those with burn plus inhalation injury (13.9%) and burn only (2.9%), while those with 81-100% TBSA burns showed no significant difference between burn only and burn plus inhalation injury. CONCLUSION: Inhalation injury remains one of the primary contributors to burn mortality. Children under the age of 3 years, however, are at a higher risk both with and without inhalation injury.

Adolescent↗

Experience with partial cricoid resection and thyrotracheal anastomosis.

Since 1973, 28 patients have undergone tracheal and subglottic resection with reconstruction by primary laryngotracheal anastomosis. Nine patients had postintubation stricture, eight had blunt trauma with cricotracheal disruption, seven had a neoplasm, two had an inhalation burn, and two had idiopathic stenosis. In all cases, the anterior cricoid arch was completely resected and a submucosal segment of the posterior cricoid plate was partially resected. A posterior shell of cricoid plate was preserved in 21 patients with intact laryngeal nerve function. Postoperatively, a Montgomery T-tube was used to stent the anastomosis and subglottic area in ten patients, all of whom had residual injury or disease at or immediately below the level of the cords. The proximal arm of the T-tube was positioned above the vocal cords. The tube was removed within 1 month in eight patients and remained for 3 and 18 months in the other two. The extent of resection varied from 2.5 to 7 cm. Tension-relieving procedures were added in 13 cases. Fourteen patients have been followed longer than 5 years, and five patients for more than 10 years. A widely patent anastomosis was maintained in 26 patients. In two patients, a partial restenosis resulted in some limitations of exercise tolerance. Voice and exercise tolerance have not deteriorated with the passage of time. Recurrent laryngeal nerve function was completely preserved in 20 of the 21 patients whose nerve function was intact before operation.

Adolescent↗

Endobronchial polyposis secondary to thermal inhalational injury.

A 28-year-old man who sustained inhalational injury in a house fire developed symptoms of chronic cough and hemoptysis requiring bronchoscopy. Two months after the initial injury, numerous endobronchial polyps were found in the trachea and throughout the bronchial tree. His symptoms have subsequently improved over a six-month period while receiving steroid therapy. To our knowledge, this delayed complication of inhalational burn injury has not been previously reported.

Adult↗

Airway obstruction in sheep with burn and smoke inhalation injuries.

The goals of this study were (i) to compare the degree and (ii) temporal changes in airway obstruction in sheep with pulmonary injury induced by smoke inhalation and/or burn; (iii) to qualitatively assess the cellular and mucous content of obstructive material; and (iv) to statistically assess a possible relationship between the degree of airway obstruction and pulmonary dysfunction. Using masked histologic slides, we estimated the degree of luminal obstruction in all cross-sectioned airways. The mean degree of bronchial, bronchiolar, and terminal bronchiolar obstruction was significantly greater in animals with smoke injury alone or combined smoke inhalation and burn (S+B) injury, compared with animals with burn injury alone or uninjured animals (P < 0.05). In S+B animals, the degree of bronchial obstruction was maximal at 24 h, with a progressive decrease over 72 h. In contrast, the degree of bronchiolar obstruction increased over time. Qualitatively, bronchial casts were largely composed of mucus at early times after injury, whereas neutrophils were the principal component of bronchiolar obstructive material. Localization of specific mucin subtypes in S+B tissues suggests that increasing bronchiolar obstruction is derived, in part, from upper airway material. Multiple linear regression analysis of airway obstruction scores compared with PaO2/FIO2 values showed a correlation coefficient of r = 0.76, with bronchial and bronchiolar scores predictive of PaO2/FIO2, (P < 0.05). These results suggest that strategies to remove or decrease formation of upper airway obstructive material may reduce its deposition into small airways and parenchyma and may improve respiratory function in victims of smoke inhalation injury.

Airway Obstruction↗

The role of the bronchial circulation in the acute lung injury resulting from burn and smoke inhalation.

Smoke inhalation in burn patients is a serious medical problem around the world. Inhalation injury increases mortality in addition to increasing infections, ventilator-days, and hospital stays. There are also large numbers of patients subjected to smoke inhalation without burns from cooking fires, burning crops and forest fires. The injury results in a fall in arterial oxygenation as a result of airway blockade, increased pulmonary transvascular fluid flux and loss of hypoxic pulmonary vasoconstriction. The changes in cardiopulmonary function are mediated at least in part by reactive oxygen and nitrogen species. Nitric oxide (NO) is generated by both inducible and constitutive isoforms of nitric oxide synthase (NOS). NO combines with superoxide to form reactive nitrogen species such as peroxynitrite. These reactive nitrogen species can be detected by measuring their reaction products such as 3-nitrotyrosine. The latter is elevated in the airway following smoke/burn injury. The control of NO formation involves poly (ADP ribose) polymerase (PARP) and its ability to up-regulate the activity of nuclear transcription factors through ribosylation. Present data also support a major role for the bronchial circulation in the injury since blockade of bronchial blood flow will also minimize the pulmonary injury. The data suggest that cytotoxins or activated cells are formed in the airway and carried to the parenchyma. These materials cause the formation of oedema and a reduction of PaO(2).

Acute Disease↗

Radionuclide lung scanning in the management of respiratory burns.

Soluble radioaerosols such as technetium-99m diethylene triamine pentacetate (DTPA) permit simple quantitative studies of alveolar-capillary permeability to be performed, since the submicronic aerosols are deposited mainly at the lung periphery and are cleared across the alveolar-capillary membrane. Regional alterations in permeability can also be noted using this radionuclide technique. We have measured the alteration in pulmonary epithelial permeability in normal subjects and in patients with inhalation burns using a computer-linked gamma-camera. In the normal volunteers, the time taken for 50% of inhaled Tc-99m DTPA to be cleared from the lungs (T1/2) was 66 minutes +/- 1sd of 12 minutes. In the 42 patients with inhalation burns, besides the T1/2, retention images of uncleared Tc-99m DTPA in the lungs were obtained to note regional differences, if any, in lung clearance arising from pulmonary epithelial damage; these patients showed increased rate of clearance (short T1/2) with mean T1/2 of 36 minutes +/- 1sd of 11 minutes, while the retention images revealed regional lung damage in moderately severe inhalation burns. In 18 patients with abnormal T1/2, 16 (89%) had abnormal bronchoscopy findings. Fifteen patients also had lung perfusion scans with Tc-99m MAA (macroaggregated albumin). The regional defects in perfusion when present were generally matched with the defects seen on ventilation scans. The Tc-99m DTPA lung clearance measurement and imaging has clinical usefulness in suspected inhalation burns.

Accidents, Occupational↗

The comparison of early fluid therapy in extensive flame burns between inhalation and noninhalation injuries.

Over the last half century, advances in treatment have changed the principal cause of death in burn patients from burn shock and wound sepsis to pulmonary sepsis, of which inhalation injury has always played a key role in morbidity and mortality. Even though Navar et al., Am. J. Surg. 1985;150:716-720 have noted that patients with inhalation injury had a mean fluid requirement of 5.8 ml/kg/% burn to achieve resuscitation from early burn shock, while patients without inhalation injury required only a mean fluid of 4.0 ml/kg/% burn, to achieve successful resuscitation in inhalation injured patients with minimum but adequate fluid has always been a challenge. To further define the difference of early fluid therapy between inhalation and noninhalation in extensively burned patients, a retrospective analysis was carried out in the Tri-Service General Hospital. Sixty-two flame burned patients (aged from 16 to 81 years-old with a mean age of 33.2+/-15.1 years: with burn size ranging from 30% to 98% TBSA with a mean burn size of 60.5+/-22.7%; 26 with inhalation injury; noninhalation 36) were reviewed during a 5-year period. The Parkland formula is the initial choice of fluid regimen with 4 ml/kg/% burn and the amount of replacement is monitored by urine output and is titrated to maintain urine output between 0.5 and 1.0 ml/kg/h. The mean amounts of fluid requirements of both inhalation and noninhalation burned patients were 3.1 +/- 1.0 and 2.3+/-0.8 ml/kg/% burn respectively (p < 0.05). Our study showed less fluid requirement for both inhalation and noninhalation injured patients in comparison with the Navar study and Parkland predictions in the first 24 h postburn. Furthermore, the inhalation injured patients definitely required volumes of fluid in excess of those required in noninhalation injured cases.

Adolescent↗