Pharmacological treatment of inhalation injury after nuclear or radiological incidents: The Chinese and German approach.

Inhalation injury is often associated with burns and significantly increases morbidity and mortality. The main toxic components of fire smoke are carbon monoxide, hydrogen cyanide, and irritants. In the case of an incident at a nuclear power plant or recycling facility associated with fire, smoke may also contain radioactive material. Medical treatments may vary in different countries, and in this paper, we discuss the similarities and differences in the treatments between China and Germany. Carbon monoxide poisoning is treated by 100% oxygen administration and, if available, hyperbaric oxygenation in China as well as in Germany. In addition, antidotes binding the cyanide ions and relieving the respiratory chain are important. Methemoglobin-forming agents (e.g., nitrites, dimethylaminophenol) or hydroxocobalamin (Vitamin B12) are options. The metabolic elimination of cyanide may be enhanced by sodium thiosulfate. In China, sodium nitrite with sodium thiosulfate is the most common combination. The use of dimethylaminophenol instead of sodium nitrite is typical for Germany, and hydroxocobalamin is considered the antidote of choice if available in cases of cyanide intoxications by fire smoke inhalation as it does not further reduce oxygen transport capacity. Systematic prophylactic use of corticosteroids to prevent toxic pulmonary edema is not recommended in China or Germany. Stable iodine is indicated in the case of radioiodine exposure and must be administered within several hours to be effective. The decorporation of metal radionuclides is possible with Ca (DTPA) or Prussian blue that should be given as soon as possible. These medications are used in both countries, but it seems that Ca (DTPA) is administered at lower dosages in China. Although the details of the treatment of inhalation injury and radionuclide(s) decorporation may vary, the general therapeutic strategy is very similar in China and Germany.

Emergency department management of smoke inhalation injury in adults.

Smoke inhalation injury portends increased morbidity and mortality in fire-exposed patients. Upper airway thermal burns, inflammation from lower airway irritants, and systemic effects of carbon monoxide and cyanide can contribute to injury. A standardized diagnostic protocol for inhalation injury is lacking, and management remains mostly supportive. Clinicians should maintain a high index of suspicion for concomitant traumatic injuries. Diagnosis is mostly clinical, aided by bronchoscopy and other supplementary tests. Treatment includes airway and respiratory support, lung protective ventilation, 100% oxygen or hyperbaric oxygen therapy for carbon monoxide poisoning, and hydroxocobalamin for cyanide toxicity. Due to its progressive nature, many patients with smoke inhalation injury warrant close monitoring for development of airway compromise.

Inhalation Injury in the Burned Patient.

Inhalation injury causes a heterogeneous cascade of insults that increase morbidity and mortality among the burn population. Despite major advancements in burn care for the past several decades, there remains a significant burden of disease attributable to inhalation injury. For this reason, effort has been devoted to finding new therapeutic approaches to improve outcomes for patients who sustain inhalation injuries.The three major injury classes are the following: supraglottic, subglottic, and systemic. Treatment options for these three subtypes differ based on the pathophysiologic changes that each one elicits.Currently, no consensus exists for diagnosis or grading of the injury, and there are large variations in treatment worldwide, ranging from observation and conservative management to advanced therapies with nebulization of different pharmacologic agents.The main pathophysiologic change after a subglottic inhalation injury is an increase in the bronchial blood flow. An induced mucosal hyperemia leads to edema, increases mucus secretion and plasma transudation into the airways, disables the mucociliary escalator, and inactivates hypoxic vasocontriction. Collectively, these insults potentiate airway obstruction with casts formed from epithelial debris, fibrin clots, and inspissated mucus, resulting in impaired ventilation. Prompt bronchoscopic diagnosis and multimodal treatment improve outcomes. Despite the lack of globally accepted standard treatments, data exist to support the use of bronchoscopy and suctioning to remove debris, nebulized heparin for fibrin casts, nebulized N-acetylcysteine for mucus casts, and bronchodilators.Systemic effects of inhalation injury occur both indirectly from hypoxia or hypercapnia resulting from loss of pulmonary function and systemic effects of proinflammatory cytokines, as well as directly from metabolic poisons such as carbon monoxide and cyanide. Both present with nonspecific clinical symptoms including cardiovascular collapse. Carbon monoxide intoxication should be treated with oxygen and cyanide with hydroxocobalamin.Inhalation injury remains a great challenge for clinicians and an area of opportunity for scientists. Management of this concomitant injury lags behind other aspects of burn care. More clinical research is required to improve the outcome of inhalation injury.The goal of this review is to comprehensively summarize the diagnoses, treatment options, and current research.

Bronchiolitis obliterans organizing pneumonia following a jalapeño grease fire.

Bronchiolitis obliterans organizing pneumonia (BOOP) is an inflammatory lung disease characterized by granulation tissue in the respiratory bronchioles, alveolar ducts and alveoli. BOOP can be caused by a number of etiologies including infection, toxic inhalation, medications, radiation, and collagen vascular disease, or it can be idiopathic. We report here a case of BOOP following inhalational exposure to a jalapeño grease fire. Capsaicin and other jalapeño-derived compounds are known causes of epithelial damage and airway inflammation but to our knowledge have never been implicated in the development of BOOP. This case adds to the growing list of exposures associated with BOOP and highlights the importance of taking a thorough exposure history in patients with lung injury of unknown etiology.

Management of cyanide toxicity in patients with burns.

The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.

Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis.

Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V(2)-receptor stimulation induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline - 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals. Highly selective V(1a)-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction.

Update on the critical care management of severe burns.

Care of the severely injured patient with burn requires correct diagnosis, appropriately tailored resuscitation, and definitive surgical management to reduce morbidity and mortality. Currently, mortality rates related to severe burn injuries continue to steadily decline due to the standardization of a multidisciplinary approach instituted at tertiary health care centers. Prompt and accurate diagnoses of burn wounds utilizing Lund-Browder diagrams allow for appropriate operative and nonoperative management. Coupled with diagnostic improvements, advances in resuscitation strategies involving rates, volumes, and fluid types have yielded demonstrable benefits related to all aspects of burn care. More recently, identification of comorbid conditions such as inhalation injury and malnutrition have produced appropriate protocols that aid the healing process in severely injured patients with burn. As more patients survive larger burn injuries, the early diagnosis and successful treatment of secondary and tertiary complications are becoming commonplace. While advances in this area are exciting, much work to elucidate immune pathways, diagnostic tests, and effective treatment regimens still remain. This review will provide an update on the critical care management of severe burns, touching on accurate diagnosis, resuscitation, and acute management of this difficult patient population.

A novel antibiotic based long-term model of ovine smoke inhalation injury and septic shock.

We modified our established and clinically relevant ARDS model of smoke inhalation injury and septic shock by administration of combined antibiotics (AB) such as piperacillin and ciprofloxacin, to more closely mimic the clinical intensive care setting. Twenty-three sheep were subjected to the injury, and allocated to four groups for a 96 h study period: sham (n=5 non-injured); control (n=6: injured); AB6h (n=6: injured, antibiotics started 6 h post-injury); AB12h (n=6: injured, antibiotics started 12 h post-injury). All sham animals survived 96 h. Control, AB6h, AB12h groups reached criteria of septic shock within 12 h post-injury. All controls died within 36 h. Eighty three percent of AB6h and fifty percent of AB12h survived 96 h. Median survival times were significantly improved in the treated groups compared with the control group: 24 h in control vs. 80.5 h in AB6h, and 65 h in AB12h animals. Combined ciprofloxacin and piperacillin therapy was effective, reduced nitric oxide production and mortality, and will allow future long-term studies in this model.

Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation.

Acute lung injury results in a severe inflammatory response, which leads to priming and activation of leucocytes, release of reactive oxygen and reactive nitrogen species, destruction of pulmonary endothelium, extravasation of protein-rich fluid into the interstitium and formation of oedema. Recently, H2S (hydrogen sulfide) has been shown to decrease the synthesis of pro-inflammatory cytokines, reduce leucocyte adherence to the endothelium and subsequent diapedesis of these cells from the microvasculature in in vivo studies, and to protect cells in culture from oxidative injury. In the present study, we hypothesized that a parenteral formulation of H2S would reduce the lung injury induced by burn and smoke inhalation in a novel murine model. H(2)S post-treatment significantly decreased mortality and increased median survival in mice. H2S also inhibited IL (interleukin)-1beta levels and significantly increased the concentration of the anti-inflammatory cytokine IL-10 in lung tissue. Additionally, H2S administration attenuated protein oxidation following injury and improved the histological condition of the lung. In conclusion, these results suggest that H2S exerts protective effects in acute lung injury, at least in part through the activation of anti-inflammatory and antioxidant pathways.

Characteristics and outcome of children with carbon monoxide poisoning with and without smoke exposure referred for hyperbaric oxygen therapy.

OBJECTIVES: To describe the clinical characteristics and outcome of children with carbon monoxide (CO) poisoning with and without smoke exposure referred for hyperbaric oxygen therapy (HBOT), and to determine the association between any of these characteristics and death. SETTING: Regional hyperbaric referral center. PATIENTS: The medical records of 150 children with CO poisoning (COP) who were treated with HBOT between August 92 and September 95 were reviewed. MEASUREMENTS/MAIN RESULTS: COP was defined as a history of probable exposure to CO, with either a carboxyhemoglobin level (COHb) > 25, or COHb < 25 with neurological, respiratory, or cardiac compromise. Major cutaneous burns were described as second degree burns over greater than 20% of the patient's total body surface area (TBSA), or third degree burns over greater than 10% of the patient's TBSA. Children extracted from a closed-space fire who had airway soot, singed facial hair/facial burns, or respiratory distress were defined as having smoke inhalation and carbon monoxide poisoning (CO/SI). CO/SI occurred in 40.1% of patients. Compared to children with COP alone, those with CO/SI were significantly more likely to have a depressed mental status upon arrival to an ED (76.3 % vs 13.6 %, P < 0.001), lower mean initial GCS (6.7 vs 14.7, P < 0.001), lower mean initial pH (7.2 vs 7.4, P < 0.001), respiratory arrest at the scene (68.5% vs 0%, P < 0.001), and cardiac arrest at the scene (25.9% vs 0%, P < 0.001). Children with CO/SI were significantly more likely to have a poor outcome (death) than children with COP alone (22.6% vs. 0%, P < 0.001). Comparing children with CO/SI who died versus survivors, there were significant differences in mean initial COHb (38.3 vs 24.3, P = 0.03), mean initial temperature upon arrival in an ED (94.9 degrees F vs 98.2 degrees, P < 0.006), respiratory arrest at the scene (92% vs 59.6%, P = 0.04), and cardiac arrest at the scene (66.7% vs 13.5%, P < 0.001). Sixty percent of children died who had a combination of risk factors of smoke inhalation, low temperature, high COHb level, and respiratory and cardiac arrest in the field. CONCLUSIONS: These preliminary data suggest that children with COP alone who are treated with HBOT are at low risk for dying regardless of initial COHb level. Children with CO/SI have a significantly higher risk of dying than those children with COP alone. A combination of smoke inhalation, low temperature, high COHb level, respiratory arrest, and cardiac arrest is highly associated with death. Prospective studies are needed to confirm and further define these associations.

Effect of radical scavengers and hyperbaric oxygen on smoke-induced pulmonary edema.

Respiratory complications, especially pulmonary edema, account for over 50% of mortalities in inhalation injuries. This study was conducted to determine the effect of free radical scavengers and hyperbaric oxygen (HBO) in vivo on reducing pulmonary edema. Adult New Zealand rabbits were allowed to breath cooled, cotton smoke until a significant inhalation lung injury was produced. Five percent of body weight lactated Ringer's solution was then administered i.v. over 2 h. The following free radical scavengers were given as bolus infusions at the beginning of fluids resuscitation: superoxide dismutase, catalase, butylated hydroxytoluene/piperonyl butoxide, and mannitol. At the completion of fluid administration, half of the subjects were given HBO treatment. Pulmonary edema was then measured as extravascular lung water and wet/dry lung weight. Results indicate that free radical scavengers or HBO reduce pulmonary edema. Free radical scavengers in conjunction with HBO showed no significant improvement over HBO or free radical scavengers alone.

Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit.

STUDY OBJECTIVE: To evaluate serial cyanide, methemoglobin, and carbon monoxide levels in smoke inhalation patients. SETTING: Regional poison center and regional toxicology treatment center. PARTICIPANTS: Seven critically ill smoke inhalation patients referred to the regional poison center. INTERVENTIONS: Peak level and half-life were determined by obtaining serial carboxyhemoglobin, cyanide, and methemoglobin levels. RESULTS: The mean observed half-life of cyanide was 3.0 +/- 0.6 hours. Methemoglobinemia was evaluated in four patients after sodium nitrite administration. The peak measured methemoglobin levels (mean, 10.5% +/- 2%; range, 7.9% to 13.4%) did not occur until a mean of 50 minutes (range, 35 to 70 minutes) following administration of sodium nitrite. The total oxygen-carrying capacity reduced by the combination of carboxyhemoglobin and methemoglobin was never more than 21% (range, 10% to 21%) in this series. CONCLUSION: The administration of sodium nitrite to smoke inhalation patients in the presence of concomitant carbon monoxide poisoning may be relatively safe.

[Experimental study on combined treatment in smoke inhalation injury].

Forty-two healthy dogs were randomly divided equally into a control group (CG) and a treated group (TG). All were inflicted with severe smoke inhalation injury and pulmonary was demonstrated. The dogs in TG were treated with injection of shenmai zhusheye, ketoprofen, anisodamine, sodium aesculin, hydrocortisone succinate, vitamin C and E, penicillin, amikacin, oxygen inhalation and airway suctioning after injury. The results showed that the increase in extravascular lung water volume, lung edema shadow in x-ray films, elevation of lung vascular resistance, carbonemia, hypoxemia, respiratory alkalosis, metabolic acidosis, dyspnea, dry and moist rales of the lungs, reduction of tidal volume, etc, were markedly improved in TG as compared with that of CG. It indicated that the pulmonary edema and lung dysfunction was markedly ameliorated in TG. The mortality was 19.1% in TG, which was significant lower than that of CG which was 47.6%.

Experimental inhalation injury with concomitant surface burn: dextran resuscitation improves lung water and oxygenation.

UNLABELLED: The role of extravascular lung water (EVLW) in the pathogenesis of inhalation injury (INH) when associated with concomitant major burn (B) remains controversial. Previous experimental models have investigated isolated INH without surface burn. This study measured the effects of isolated and combined INH on EVLW and pO2 in a porcine experimental model. The beneficial effects of early resuscitation with dextran-40 (DEX) were assessed, using a control group receiving standard Parkland formula (LR). In the first part of the study (INH vs. INH + B), a group of animals with a standardized INH was compared to a group also receiving a standardized 40% BSA third-degree surface burn (n = 8, each group). With serial measurements for 5 hours, EVLW was only modestly increased unless INH was accompanied by surface burn: 20.3 +/- 4.2 vs. 32.0 +/- 4.1 ml/kg at 5 hours (p less than 0.01). Similarly, pO2 fell much more dramatically in the INH + B group, 61 +/- 5 vs. 37 +/- 5 torr (p less than 0.05). The second part of the study compared standard Parkland crystalloid resuscitation with dextran-40 resuscitation in animals receiving a combined INH + B injury (LR vs. DEX, n = 8, each group). DEX resuscitation resulted in substantially lower accumulation of EVLW out to 5 hours, 34.1 +/- 5.0 vs. 13.1 +/- 3.0 ml/kg (p less than 0.01), and significantly better pO2, 35 +/- 5 vs. 64 +/- 4 torr (p less than 0.01). CONCLUSIONS: Inhalation injury did not dramatically increase EVLW in this animal model unless accompanied by concomitant major surface burn. The deterioration in EVLW and pO2 seen in the combined injury was significantly improved with DEX resuscitation when compared to standard crystalloid resuscitation. Further study is indicated and clinical trials may be warranted.

Suspected cyanide poisoning in smoke inhalation: complications of sodium nitrite therapy.

A 78 year old man was found comatose, apneic, and asystolic after closed-space smoke inhalation. He was successfully resuscitated to pulse and blood pressure at the scene. A cyanide component to the poisoning was suspected and two 300 mg doses of sodium nitrite were administered, resulting in significant hypotension. Although high methemoglobin levels were not induced, when added to simultaneously obtained carboxyhemoglobin levels, the total amount of non-oxygen transporting hemoglobin remained nearly constant for about 4-1/2 hours before hyperbaric oxygen (HBO) therapy could be administered. The patient later died in multi-organ system failure. Admission whole blood cyanide level was only 0.34 mcg/mL. These sodium nitrite adverse effects can be avoided by slow intravenous infusion and by administering only recommended doses. In smoke inhalation victims with suspected cyanide poisoning, sodium thiosulfate should be administered first, and sodium nitrite withheld until after the patient is receiving HBO therapy. When available, hydroxocobalamin (which neither induces methemoglobinemia nor causes hypotension) may be the specific cyanide antidote of choice for victims of smoke inhalation.