Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury

2003 ◽  
Vol 105 (5) ◽  
pp. 621-628 ◽  
Author(s):  
Perenlei ENKHBAATAR ◽  
Kazunori MURAKAMI ◽  
Katsumi SHIMODA ◽  
John SALSBURY ◽  
Robert COX ◽  
...  
Keyword(s):  
Burn Injury ◽  
Recovery Period ◽  
Inhalation Injury ◽  
Significant Inhibition ◽  
Smoke Inhalation ◽  
Stroke Work ◽  
Smoke Inhalation Injury ◽  
Stroke Work Index ◽  
Nitrite Nitrate ◽  
Plasma Nitrite

Massive cutaneous burn combined with smoke inhalation causes high mortality in fire victims. Cyclo-oxygenase (COX) and inducible nitric oxide (NO) synthase (iNOS) have been shown to be up-regulated in burn injury. Ketorolac, a non-steroidal, anti-inflammatory agent (NSAID), inhibits prostaglandin and thromboxane synthesis through inhibition of COX. NSAIDs have been shown to down-regulate iNOS. Thus we hypothesized that treatment with ketorolac would attenuate burn/smoke-related cardiopulmonary derangements. We conducted a fully controlled long-term laboratory investigation in an Intensive Care Unit setting. Eighteen female sheep were surgically prepared for chronic study. After a recovery period of 5 days, a tracheotomy was performed under ketamine/halothane anaesthesia. Sheep were given a 40% total body surface third-degree burn and insufflated with cotton smoke (48 breaths, <40 °C). Sheep were divided into three groups: sham (not injured and not treated; n=6), control (injured, but not treated; n=6) and treated (injured and administered ketorolac 60 mg/day; n=6). The sham group had stable cardiopulmonary and systemic haemodynamics. Control animals showed depressed cardiopulmonary function, decreased pulmonary gas exchange, increased pulmonary microvascular leakage and decreased left ventricle stroke work index with elevated left atrial pressure. Systemic vascular leak in control animals was evidenced by robust haemoconcentration (haematocrit and fluid net balance). Treatment with ketorolac prevented all of these morbidities. Post-treatment with ketorolac also resulted in significant inhibition of elevated plasma nitrite/nitrate levels in control animals. These results suggest that ketorolac may ameliorate cardiopulmonary morbidity, at least in part, by inhibiting excessive NO.

scholarly journals Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep

2003 ◽  
Vol 285 (1) ◽  
pp. L240-L249 ◽  
Author(s):  
Katsumi Shimoda ◽  
Kazunori Murakami ◽  
Perenlei Enkhbaatar ◽  
Lillian D. Traber ◽  
Robert A. Cox ◽  
...  
Keyword(s):  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Lung Edema ◽  
Edema Formation ◽  
Smoke Inhalation Injury ◽  
Chronic Study ◽  
Inhalation Burn ◽  
Nitrite Nitrate ◽  
Plasma Nitrite

We investigated the role of the nuclear enzyme poly (ADP ribose) synthetase (PARS) in the pathogenesis of combined burn and smoke inhalation (burn/smoke) injury in an ovine model. Eighteen sheep were operatively prepared for chronic study. PARS inhibition was achieved by treatment with a novel and selective PARS inhibitor INO-1001. The PARS inhibitor attenuated 1) lung edema formation, 2) deterioration of gas exchange, 3) changes in airway blood flow, 4) changes in airway pressure, 5) lung histological injury, and 6) systemic vascular leakage. Lipid oxidation and plasma nitrite/nitrate (stable breakdown products of nitric oxide) levels were suppressed with the use of INO-1001. We conclude that PARS inhibition attenuates various aspects of the pathophysiological response in a clinically relevant experimental model of burn/smoke inhalation injury.

Pulmonary changes in a mouse model of combined burn and smoke inhalation-induced injury

2008 ◽  
Vol 105 (2) ◽  
pp. 678-684 ◽  
Author(s):  
Akio Mizutani ◽  
Perenlei Enkhbaatar ◽  
Aimalohi Esechie ◽  
Lillian D. Traber ◽  
Robert A. Cox ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Murine Model ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Inos Mrna ◽  
Myeloperoxidase Activity ◽  
Smoke Inhalation Injury ◽  
Injury Group

The morbidity and mortality of burn victims increase when burn injury is combined with smoke inhalation. The goal of the present study was to develop a murine model of burn and smoke inhalation injury to more precisely reveal the mechanistic aspects of these pathological changes. The burn injury mouse group received a 40% total body surface area third-degree burn alone, the smoke inhalation injury mouse group received two 30-s exposures of cotton smoke alone, and the combined burn and smoke inhalation injury mouse group received both the burn and the smoke inhalation injury. Animal survival was monitored for 120 h. Survival rates in the burn injury group, the smoke inhalation injury group, and the combined injury group were 70%, 60%, and 30%, respectively. Mice that received combined burn and smoke injury developed greater lung damage as evidenced by histological changes (septal thickening and interstitial edema) and higher lung water content. These mice also displayed more severely impaired pulmonary gas exchange [arterial Po2(PaO2)/inspired O2fraction (FiO2) < 200]. Lung myeloperoxidase activity was significantly higher in burn and smoke-injured animals compared with the other three experimental groups. Plasma NO2−/NO3−, lung inducible nitric oxide synthase (iNOS) activity, and iNOS mRNA increased with injury; however, the burn and smoke injury group exhibited a higher response. Severity of burn and smoke inhalation injury was associated with more pronounced production of nitric oxide and accumulation of activated leukocytes in lung tissue. The murine model of burn and smoke inhalation injury allows us to better understand pathophysiological mechanisms underlying cardiopulmonary morbidity secondary to burn and smoke inhalation injury.

519 Retrospective Pilot Study to Examine Potential Predictors of a Standardized Scoring System for Smoke Inhalation Injury

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S97-S98
Author(s):  
Joshua Frost ◽  
Grant Sorensen ◽  
Nicole Van Spronsen ◽  
Jordan Howell ◽  
Donna Ayala ◽  
...  
Keyword(s):  
Scoring System ◽  
Burn Injury ◽  
Inhalation Injury ◽  
Physical Exam ◽  
Smoke Inhalation ◽  
Continuous Variables ◽  
Diagnostic Significance ◽  
Smoke Inhalation Injury ◽  
Carbon Particles ◽  
Significant Difference

Abstract Introduction Smoke inhalation injury is strongly associated with increased morbidity/mortality. Bronchoscopy is used to diagnosis smoke inhalation injury, but its interpretation is subjective. This study sought to assess diagnostic significance of physical exam, history, location, and adjunct studies characteristically performed on patients suspected of smoke inhalation by comparing these findings to outcomes. The primary goal was to examine variables that could be used to create an accurate smoke inhalation injury scoring system in order to develop an objective method that considers the severity of inhalation injury. Methods This retrospective study evaluated demographics, clinical presentation, carboxyhemoglobin level, intubation on arrival, bronchoscopy, comorbidities, hospital course, and outcomes associated with smoke inhalation. Bronchoscopy findings included: red mucosa, carbon particles at carina, and numerical score (1–4). The primary outcome was resuscitation fluid required in the first 24 hours of treatment compared to that predicted by the modified Brooke formula (2cc*weight in kg* Total Burn Surface Area). If the patient received more fluid than predicted, this was considered positive for smoke inhalation. Differences between predictor/outcome variables were determined using Wilcoxon rank sum test for continuous variables and Chi-squared test for categorical. Results A positive bronchoscopy score was defined on the condition of having positive physical exam finding and/or bronchoscopy score 1–4. Physical exam findings consisted of soot or carbon sputum present on the patient along with hoarseness, wheezing, or a red oropharynx on physical exam. If the patient met one of these conditions, we considered this a positive result. Inclusion criteria: age 18–89, admission from 1/1/2004 and 5/31/18, and diagnosis of smoke inhalation injury/burn injury. There was a significant difference in positive bronchoscopy between those positive for our condition of inhalation injury and no injury (p&lt; 0.001; Table 1). Patients with a positive bronchoscopy score were 9 times more likely (OR=9.91, 95% CI = 2.8–35.01) to be diagnosed with inhalation injury as compared to those without a positive bronchoscopy score. Conclusions These results display the importance of bronchoscopy in suspected smoke inhalation injury and reinforce the need for an objective bronchoscopy assessment. Future studies can build upon these results by creating an objective scoring system to guide providers performing bronchoscopy. Applicability of Research to Practice Due to the 9-fold benefit of performing bronchoscopy, it should be the primary tool used to assess potential smoke inhalation injury; other tests may be secondary in nature.

Sem And Tem Observations of Rat Trachea and Lung After Inhalation Injury and Cutaneous Burn In a Rat Model

1999 ◽  
Vol 5 (S2) ◽  
pp. 1176-1177
Author(s):  
P.C. Langlinais ◽  
D.W. Mozingo ◽  
M.A. Dubick ◽  
S.C. Carden ◽  
C.W. Goodwin
Keyword(s):  
Burn Injury ◽  
Small Animal ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Tree Bark ◽  
Sprague Dawley ◽  
Smoke Inhalation Injury ◽  
Severe Burns ◽  
Total Body ◽  
Large Animals

Inhalation injury is present in 32-38% of patients with severe burns and is associated with an increase of 20-84% above the mortality expected based on age and burn size alone. Most previous studies of smoke inhalation injury have utilized large animals such as the sheep and we have previously reported a TEM and SEM study of lung injury in the sheep. The present observations are part of a study to develop a small animal combined model of smoke inhalation and surface burn.Adult, male Sprague-Dawley rats were used. Animals were anesthetized and randomly assigned to one of four groups. Groups 1 and 2 received a 20% total body area surface (TBSA) full thickness scald burns while groups 3 and 4 were sham treated. Five hours after burn injury, rats were placed in a nose only exposure device and half of each group was exposured to either room air alone or room temperature tree bark smoke for 16.25 minutes.

scholarly journals Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature

2020 ◽  
Vol 36 (4) ◽  
pp. 130-140
Author(s):  
Megan K. Phelps ◽  
Logan M. Olson ◽  
Megan A. Van Berkel Patel ◽  
Molly J. Thompson ◽  
Claire V. Murphy
Keyword(s):  
Mechanical Ventilation ◽  
Burn Injury ◽  
Data Extraction ◽  
Bleeding Risk ◽  
Clinical Findings ◽  
Inhalation Injury ◽  
Adult Patients ◽  
Smoke Inhalation ◽  
Clinical Effects ◽  
Smoke Inhalation Injury

Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.

Pathophysiology of acute lung injury in combined burn and smoke inhalation injury

2004 ◽  
Vol 107 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Perenlei ENKHBAATAR ◽  
Daniel L. TRABER
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Burn Injury ◽  
Surgical Excision ◽  
Inhalation Injury ◽  
Burn Injuries ◽  
Morbidity And Mortality ◽  
Smoke Inhalation ◽  
Therapeutic Approaches ◽  
Smoke Inhalation Injury

In the U.S.A., more than 1 million burn injuries occur every year. Although the survival from burn injury has increased in recent years with the development of effective fluid resuscitation management and early surgical excision of burned tissue, the mortality of burn injury is still high. In these fire victims, progressive pulmonary failure and cardiovascular dysfunction are important determinants of morbidity and mortality. The morbidity and mortality increases when burn injury is associated with smoke inhalation. In the present review, we will describe the pathophysiological aspects of acute lung injury induced by combined burn and smoke inhalation and examine various therapeutic approaches.

Pathophysiological Basis of Smoke Inhalation Injury

Physiology ◽  
2003 ◽  
Vol 18 (3) ◽  
pp. 125-129 ◽  
Author(s):  
Kazunori Murakami ◽  
Daniel L. Traber
Keyword(s):  
Respiratory Failure ◽  
Burn Injury ◽  
Physiological Responses ◽  
Treatment Strategies ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury

Smoke inhalation injury results in serious respiratory failure. When smoke inhalation injury is combined with burn injury or pneumonia, the physiological responses are different and more severe than those of smoke inhalation injury alone. Treatment strategies should be planned based on these pathophysiological aspects.

Pathophysiological analysis of combined burn and smoke inhalation injuries in sheep

2001 ◽  
Vol 280 (6) ◽  
pp. L1233-L1241 ◽  
Author(s):  
Kazutaka Soejima ◽  
Frank C. Schmalstieg ◽  
Hiroyuki Sakurai ◽  
Lillian D. Traber ◽  
Daniel L. Traber
Keyword(s):  
Burn Injury ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Lung Edema ◽  
Pulmonary Vascular Permeability ◽  
Smoke Inhalation Injury ◽  
Combined Injury ◽  
Injury Group ◽  
Initial Depression ◽  
Two Phases

We investigated the pathophysiological alterations seen with combined burn and smoke inhalation injuries by focusing on pulmonary vascular permeability and cardiopulmonary function compared with those seen with either burn or smoke inhalation injury alone. To estimate the effect of factors other than injury, the experiments were also performed with no injury in the same experimental setting. Lung edema was most severe in the combined injury group. Our study revealed that burn injury does not affect protein leakage from the pulmonary microvasculature, even when burn is associated with smoke inhalation injury. The severity of lung edema seen with the combined injury is mainly due to augmentation of pulmonary microvascular permeability to fluid, not to protein. Cardiac dysfunction after the combined injury consisted of at least two phases. An initial depression was mostly related to hypovolemia due to burn injury. It was improved by a large amount of fluid resuscitation. The later phase, which was indicated to be a myocardial contractile dysfunction independent of the Starling equation, seemed to be correlated with smoke inhalation injury.

Sign in / Sign up

Export Citation Format

Share Document