Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model.

It is generally assumed that the development of bacterial pneumonia becomes possible when the dose of inhaled or aspirated pathogens overwhelms the respiratory tract host defence system, but this hypothesis has not yet been tested either clinically or experimentally. This study evaluated inoculum dose in relation to onset of experimental pneumococcal pneumonia, and estimated the median effective dose resulting in pneumonia in healthy New Zealand White rabbits (mean+/-sd 4.75+/-0.25 kg (n = 27)). Rabbits were endobronchially inoculated with increasing doses of Streptococcus pneumoniae and pneumonia onset was observed over the following 96 h. The diagnostic approach was based on the Clinical Pulmonary Infection Score, modified for use in rabbits. Inoculation of S. pneumoniae at doses of >4.60 log(10) cfu made the development of pneumonia in rabbits more predictable (up to 90%). Lower doses of bacteria failed to cause pneumonia in 80% of inoculated animals. The median effective dose was estimated by means of logistical regression, probit analyses and the Reed-Muench method, and corresponded to 4.32, 4.38 and 4.67 log(10) cfu, respectively. It is speculated that development of pneumococcal pneumonia becomes more likely when the inoculum dose exceeds a threshold of antibacterial protection, making inoculum dose a risk factor for disease onset.

Delayed partial liquid ventilation shows no efficacy in the treatment of smoke inhalation injury in swine.

In an earlier neonatal porcine model of smoke inhalation injury (SII), immediate postinjury application of partial liquid ventilation (PLV) had dramatic beneficial effects on lung compliance, oxygenation, and survival over a 24-h period. To explore the efficacy of PLV following SII, we treated animals at 2 and 6 h after SII and followed them for 72 h. Pigs weighing 8-12 kg were sedated and pharmacologically paralyzed, given a SII, and placed on volume-cycled, pressure-limited ventilation. Animals were randomized to three groups: group I (+SII, no PLV, n = 8), group II (+SII, PLV at 2 h, n = 6), and group III (+SII, PLV at 6 h, n = 7). Ventilatory parameters and arterial blood gasses were obtained at scheduled intervals. The PLV animals (groups II and III) followed a worse course than group I (no PLV); PLV groups had higher peak and mean airway pressures, oxygenation index, and rate-pressure product (a barotrauma index) and lower lung compliance and arterial partial pressure of oxygen-to-inspired oxygen fraction ratio (all P < 0.05). PLV conferred no survival advantage. The reported beneficial effects of PLV with other models of acute lung injury do not appear to extend to the treatment of SII when PLV is instituted in a delayed manner. This study was not able to validate the previously reported beneficial effects of PLV in SII and actually found deleterious effects, perhaps reflecting the predominance of airway over alveolar disease in SII.

Wood smoke particles generate free radicals and cause lipid peroxidation, DNA damage, NFkappaB activation and TNF-alpha release in macrophages.

The present study investigated the generation of free radicals by wood smoke and cellular injuries caused by these radicals. Wood smoke was collected after thermolysis of western bark. Electron spin resonance (ESR) techniques were used to measure both carbon-centered radicals and generation of reactive oxygen species (ROS) by wood smoke. Wood smoke, in the presence of H(2)O(2), was found to be able to generate hydroxyl radical (.OH). DNA strand breakage was measured by exposing wood smoke to lambda Hind III fragments using gel electrophoresis. Wood smoke combined with H(2)O(2) caused DNA damage. Sodium formate, an .OH radical scavenger, or deferoxamine, a metal chelator, inhibited the DNA damage. Cellular DNA damage was also measured in cultured RAW 264.7 mouse macrophage cells by the single cell gel (SCG) electrophoresis assay. Cells were exposed to wood smoke samples for various times and significant DNA damage was observed. Elemental analysis was performed on the filter samples and the presence of Fe was noteworthy. Wood smoke is also able to cause lipid peroxidation, activate nuclear transcription factor, NFkappaB, and enhance the release of TNF-alpha from RAW 264. 7 cells. The results indicate that the free radicals generated by wood smoke through the reaction of Fe with H(2)O(2) are able to cause DNA and cellular damage and may act as a fibrogenic agent.

Management of the burn wound.

Few features of the burn victim attract more attention than the damage or destruction of the skin from thermal injury. Management of the resultant burn wound is the systematic application of knowledge and technique to promote and facilitate closure of integumentary disruption. The role of the professional nurse in the management of burn wounds, often within the milieu of critical care, can be uniquely challenging and especially rewarding. This article reviews management of the burn wound with emphasis on methods, techniques, and procedures used in contemporary burn wound treatment. The article also includes nursing care plans of selected nursing diagnoses for organizing and facilitating the nursing care process.

The use of perfluorocarbon-associated gas exchange to improve ventilation and decrease mortality after inhalation injury in a neonatal swine model.

Patients with tracheobronchial disease frequently require mechanical ventilation during therapy and experience iatrogenic complications such as barotrauma and volutrauma. The purpose of this study was to determine whether perfluorocarbon-associated gas exchange (PAGE) results in lower ventilatory pressures and more efficient ventilation than that provided by conventional ventilation after tracheobronchial mucosal injury caused by smoke inhalation in neonatal piglets. Ten piglets were used for this prospective, randomized study. After administration of a severe smoke inhalation injury, the piglets were randomly assigned to either the perfluorocarbon or control groups. Group 1 served as the control population and received standard (time-cycled, volume-limited) mechanical ventilation. Ventilator settings were adjusted to maintain physiological pH and PO2 at the lowest tidal volume, rate, and end-expiratory pressure possible throughout the study period. Group 2 was administered intratracheal perfluorocarbon as well as identical mechanical ventilation to attain the same physiological pH and PO2. Oxygenation index, peak and mean airway pressures, and arterial blood gas levels were measured throughout the study period and subjected to statistical analysis. Histological comparison of airway and parenchymal tissues confirmed identical patterns of smoke injury in both groups. Carbon monoxide levels were the same in both groups. There was significant barotrauma and volutrauma in the control group, but none in the PAGE group. All controls died from 13 to 17 hours after injury; one PAGE pig died at 23 hours with all others surviving past 24 hours (P = .0021). Peak, plateau, and mean airway pressures were all significantly higher (P < .05) past 12 hours after injury and continued to increase until death in the controls. Arterial blood gases showed significantly (P < .05) decreased pH, PO2, and elevated PcO2 levels in the control group past 12 hours after injury. The oxygenation index was significantly elevated (P < .05) in the control group past 12 hours after injury. PAGE shows potential for improving ventilation and survival immediately after severe smoke inhalation injury and may have clinical applications in other nonhomogeneous lung injuries.

Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock.

BACKGROUND: Nitric oxide synthase (NOS) inhibition has been shown to potentiate lipopolysaccharide (LPS) associated pulmonary hypertension, which may worsen right ventricular (RV) dysfunction and decrease cardiac output during sepsis. This study evaluates whether inhaled nitric oxide can ameliorate the adverse cardiopulmonary effects of NOS inhibition during endotoxemia. METHODS: After an infusion of Escherichia coli LPS (200 micrograms/kg), animals were resuscitated with saline (1 mL/kg/min) and observed for 3 hours while mechanically ventilated (FIO2, 0.6; VT, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). The LPS group (n = 6) received no additional treatment. The N-nitro-L-arginine methyl ester (NAME) group (n = 5) received L-NAME, a NOS inhibitor, 50 micrograms/kg/min for the last 2 hours. The NO+NAME group (n = 6) received inhaled NO (40 ppm) and L-NAME for the last 2 hours. The control group (n = 5) received only saline without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours. RESULTS: L-NAME worsened LPS-associated pulmonary hypertension and RV dysfunction as reflected by decreased RV ejection fraction. Inhaled nitric oxide significantly decreased pulmonary hypertension and improved RV ejection fraction and stroke work index. There were no adverse systemic effects. CONCLUSIONS: Inhaled nitric oxide reverses pulmonary hypertension seen with L-NAME treatment during endotoxemia and may be a useful adjunct to NOS inhibition in the treatment of septic shock.

Effects of inhaled nitric oxide on right ventricular function in endotoxin shock.

Sepsis has been shown to cause right ventricular (RV) dysfunction, which may be related to pulmonary hypertension and increased RV afterload. This study evaluates the effects of inhaled nitric oxide (NO), a selective pulmonary vasodilator, on RV function in a porcine model of endotoxemia. After an infusion of Escherichia coli lipopolysaccharide (LPS; 200 micrograms/kg), animals were resuscitated with saline (1 mL/kg/min) and observed for 3 hours while being mechanically ventilated (Fio2 = 0.6, tidal volume = 12 mL/kg, and peak end-expiratory pressure = 5 cm H2O). The LPS group (n = 5) received no additional treatment. The NO group (n = 5) received inhaled NO (40 ppm) for the last 2 hours. The control group (n = 5) received only saline without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours. LPS resulted in pulmonary hypertension and RV dysfunction as indexed by a decreased RV ejection fraction and increased RV end-diastolic volume. Inhaled NO significantly decreased pulmonary hypertension and significantly increased RV ejection fraction and oxygen delivery without adverse effects. In conclusion, inhaled NO significantly improved pulmonary hypertension and RV dysfunction in a porcine model of endotoxemia and should be a useful therapeutic modality in selected septic patients.

The pulmonary effect of nitric oxide synthase inhibition following endotoxemia in a swine model.

OBJECTIVE: To evaluate the pulmonary effect of treatment with N-nitro-L-arginine methyl ester (NAME) with and without inhaled nitric oxide (NO) in a swine model of endotoxemia. DESIGN: Randomized controlled trial. SETTING: Laboratory. INTERVENTIONS: Following a 20-minute intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (200 micrograms/kg), animals were resuscitated with saline solution (1 mL/kg per minute) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen [FIO2], 0.6; tidal volume, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n = 6) received no additional treatment; group 2 (NAME, n = 5) received NAME (3 mg/kg per hour) for the last 2 hours; group 3 (NO, n = 6) received NAME (3 mg/kg per hour) and inhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n = 5) received only saline solution without LPS. MAIN OUTCOME MEASURES: Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique was performed at 3 hours. The wet-to-dry lung weight ratio was measured following necropsy. RESULTS: Administration of LPS resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia with increased ventilation perfusion ratio mismatching. None of these changes were attenuated by NAME treatment alone but all were significantly improved by the simultaneous administration of inhaled NO. CONCLUSIONS: Systemic NO synthase inhibition failed to restore hypoxic pulmonary vasoconstriction following LPS administration. The deleterious effects of endotoxemia on pulmonary function can be improved by inhaled NO but not by systemic inhibition of NO synthase.

Effect of inhaled nitric oxide on pulmonary function after sepsis in a swine model.

BACKGROUND: Inhaled nitric oxide (NO) has been shown to improve sepsis induced pulmonary dysfunction. This study evaluated the mechanism by which inhaled NO improves pulmonary function in a porcine sepsis model. METHODS: After an infusion of Escherichia coli lipopolysaccharide (LPS, 200 micrograms/kg), animals were resuscitated with saline solution (1 ml/kg/min) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen, 0.6; tidal volume, 12 ml/kg; positive end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n = 6) received no additional treatment. Group 2 (NO, n = 6) received inhaled NO (40 ppm) for the last 2 hours. Group 3 (control, n = 5) received only saline solution without LPS. Cardiopulmonary variables and blood gases were measured serially. Multiple inert gas elimination technique was performed at 3 hours. Wet to dry lung weight ratio was measured after necropsy. RESULTS: Lipopolysaccharide resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia. Multiple inert gas elimination technique analysis indicated a significant increase in blood flow to true shunt and high ventilation perfusion distribution (VA/Q) areas with an increased dispersion of VA/Q distribution. All of these changes were significantly attenuated by NO. CONCLUSIONS: Inhaled NO significantly improved LPS induced VA/Q mismatching by decreasing both true shunt and high VA/Q areas, by decreasing pulmonary edema, and by redistributing blood flow from true shunt to ventilated areas.

The effect of inhaled nitric oxide on smoke inhalation injury in an ovine model.

Smoke inhalation is a significant comorbid factor in thermal trauma. The effect of inhaled nitric oxide (NO) on smoke inhalation injury was evaluated in an ovine model. Following smoke exposure, group 1 animals (n = 9) spontaneously breathed room air, and group 2 animals (n = 8) breathed 20 parts per million of NO in air for 48 hours. Cardiopulmonary variables and blood gases were serially measured; bronchoalveolar lavage (BAL) was performed and wet-to-dry lung weight ratios (W/D) determined at 48 hours. Pulmonary vasoconstriction following smoke inhalation was significantly attenuated by inhaled NO (p < 0.05), which exerted no apparent effect on the systemic circulation. In group 2, the serial decline in pulmonary oxygenation was less than in group 1, consistent with a smaller physiologic shunt (p < 0.05). There were no significant differences in W/D, lung compliance, BAL fluid analysis results, or histologic evaluation findings between the two groups. These results suggest that inhaled NO exerted beneficial effects on pulmonary arterial hypertension and oxygenation following smoke inhalation without apparent amelioration of airway inflammation.

Plasma cytokines following thermal injury and their relationship with patient mortality, burn size, and time postburn.

We measured plasma levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) following thermal injury. Cytokine levels in the plasma of 27 burned patients were serially screened by ELISA and compared with cytokine levels in 16 healthy laboratory employees. The relationships between cytokine concentrations and patient mortality, burn size, and time postburn were examined. Plasma samples with detectable amounts of IL-1 beta and IL-6 were significantly more frequent in burned patients than in controls, whereas TNF alpha was undetectable in most plasma samples. All nonsurviving burned patients had detectable IL-6 levels; these were significantly higher than those of surviving patients. The IL-1 beta and IL-6 concentrations were highest during the first week after injury and declined over time. The IL-1 beta concentrations were positively correlated with burn size. These findings suggest that IL-1 beta and IL-6 may influence metabolic and immunologic responses in the first few weeks following thermal injury. Tumor necrosis factor alpha was transiently elevated in a small subpopulation of burned patients with no obvious relationship to burn size or time postburn.

Granulocyte oxidative activity after thermal injury.

BACKGROUND: Alterations in granulocyte function after thermal injury have been described. We have serially studied the level of granulocyte cytosolic peroxidase activity in 23 thermally injured patients during the first 6 weeks after injury. The patients' mean age and burn size were 35.1 +/- 15.7 years and 41.6% +/- 16.8% (range, 18% to 88%), respectively. Fourteen patients had concomitant inhalation injury, and the overall mortality rate was 4.3%. METHODS: Purified granulocytes were obtained from peripheral blood after red cell lysis and Ficoll-Hypaque (Pharmacia Inc., Piscataway, N.J.) gradient separation. Cells were loaded with dichlorofluorescin diacetate, and baseline fluorescence was measured by flow cytometry. After phorbol myristate acetate stimulation, fluorescence was measured again. Cells from unburned normal subjects were used as daily controls. RESULTS: The data are expressed as percent of stimulated control granulocyte fluorescence. Unstimulated patient granulocytes demonstrated a significantly higher baseline activity than did unstimulated controls (22.9% vs 15.4%; p < 0.05). Mean fluorescence from stimulated granulocytes was 114% of the control values (p < 0.05). CONCLUSIONS: Granulocytes from thermally injured patients exhibited a baseline increase in cytosolic oxidase activity, suggesting in vivo activation and a greater than normal oxidase activity after in vitro stimulation.

Simultaneous determination of lactulose and mannitol in urine of burn patients by gas-liquid chromatography.

Ratios of lactulose/mannitol excretion in urine have been used to assess the extent of intestinal permeability in various disease and trauma conditions. Reported studies have used this technique to correlate altered gastrointestinal mucosal permeability to translocation of bacteria and endotoxin, leading to occult sepsis in burn patients. Enzymatic methods of analysis for urine concentrations of mannitol and lactulose were used in these studies. We have found that urine from patients with severe burns frequently contains compounds that interfere with the enzymatic methods. We describe using gas-liquid chromatography to determine mannitol and lactulose simultaneously in the urine of burn patients. To avoid the multiple peaks for the anomeric forms of the reducing sugars during precolumn trimethylsilyl derivatization, we converted the sugars to oximes before the silylation step. The method gave good recoveries of mannitol and lactulose added to burn patients' urine samples. Unlike the enzymatic methods, gas-liquid chromatography eliminates the effect of interfering compounds and allows for the simultaneous determination of both sugars in urine samples.

Dissociation of blood volume and flow in regulation of salt and water balance in burn patients.

The relationship between effective blood volume and related hormones in burn patients following resuscitation is not well understood. Previous reports have suggested that hormone secretion is altered by a resetting of neural control mechanisms. Serum and urine sodium, plasma renin activity, serum ADH, cardiac index, effective renal plasma flow, and total blood volume were measured in seven burn patients (mean age, total burn size, and postburn day: 32 years, 56%, and 9 days, respectively). The same values (with the exception of cardiac index and blood volume) were measured in 10 control patients (mean age, 24 years). The blood volume of patients was measured by 51chromium red blood cell (RBC) labeling and compared to normal predicted values based on body surface area and sex. Mean serum sodium and osmolality were 138 mmol/L (millimolar) and 286 mosm/kg, respectively, in both patients and control subjects. Mean +/- standard error of the mean total blood volume in the patients was low, 81% +/- 4% of predicted values. Cardiac index and renal plasma flow were significantly elevated. Plasma renin activity and antidiuretic hormone (ADH) levels were elevated and altered in the direction expected from blood volume measurements despite the findings of increased blood flow. Dissociation of organ flow and hormonal response suggests that simultaneous direct blood volume measurements are necessary to elucidate factors other than altered neural control settings to explain hormonal changes in the flow phase of injury. Depressed total blood volume appears to promote elevated ADH levels in burn patients following resuscitation. Whether there is an additional role of altered neural control settings remains to be established.

Implementing nutritional therapy in the thermally injured patient.

Providing adequate nutritional support is an important adjuvant therapy in the management of thermal injuries. Technological advances in both enteral and parenteral nutrition have enabled clinicians to administer large amounts of essential nutrients to critically ill patients who frequently cannot or will not take these nutrients orally. The use of any method of nutritional support requires careful administration and scheduled monitoring to ensure its safety and efficacy. Critical care nurses have an integral role in assuring that appropriate nursing care and monitoring measures are performed.

Effects of granulocyte-macrophage colony-stimulating factor in burn patients.

We studied the effects of granulocyte-macrophage colony-stimulating factor in burn patients. Serial measurements of granulocyte oxidative function were obtained in treated patients and in a group of controls matched for age and total burn size. The administration of granulocyte-macrophage colony-stimulating factor resulted in a 50% increase in mean leukocyte counts. Both groups showed significant baseline increases in granulocytic cytosolic oxidative function. Treated patients showed normal stimulated cytosolic oxidative function, which was significantly depressed compared with that of untreated patients. Myeloperoxidase activity was increased in treated patients during the first postburn week but then declined to normal levels. Untreated patients had a significant increase in myeloperoxidase activity for the first 3 weeks following injury. Untreated patients exhibited a significant decrease in superoxide activity during the second 3 weeks following injury. Treated patients demonstrated normal superoxide activity.