Biomedical subjects

W G Cioffi

Publications and source records attributed to W G Cioffi.

At least 91 records · Page 5Linked to original sources

PubMed1996

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.

Administration, Inhalation↗

PubMed1995

Thermal trauma resulting from motor vehicle operation or maintenance.

Burn injury may result from the operation or maintenance of motor vehicles. We reviewed the experience of one burn center with injuries related to motor vehicle use over the 6 year period 1987-1992. One hundred and fifty patients with motor vehicle related burns were identified comprising 11.3% of all admissions for this period. The mean extent of burn injury was 22.8% total body surface area with a mean full thickness (third degree) burn size of 11.7%. The average hospital length of stay was 42.41 days. The most common mechanisms of injury were collisions resulting in fire (n = 48), carburetor priming (n = 37) and scalding from radiator fluid contact (n = 27). Burns resulting from vehicle operation or maintenance are costly and potentially preventable.

Accidents, Traffic↗

PubMed1995

Peritoneal lavage in the diagnosis of acute surgical abdomen following thermal injury.

Intraperitoneal sepsis is difficult to diagnose in thermally injured patients. We reviewed the use of diagnostic peritoneal lavage (DPL) in burn patients suspected of having intraperitoneal infection. Seventeen patients were identified in whom celiotomy, autopsy, or complete recovery could be used to validate the lavage results. A lavage was considered positive if there were greater than 500 white blood cells per mm3 or if microorganisms were present on Gram stain. Six patients had a positive DPL and 11 patients had a negative DPL. There were six true positive, no false positive, ten true negative, and one false negative studies resulting in a sensitivity of 0.86, specificity of 1.00, and diagnostic accuracy of 94%. No complications related to the DPL occurred. This procedure is safe and will rapidly and reliably discriminate between patients needing urgent celiotomy and those requiring further investigation to identify a source of sepsis.

Abdomen, Acute↗

PubMed1995

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.

Administration, Inhalation↗

PubMed1995

Inhaled nitric oxide in acute lung disease.

The recognition that inhaled nitric oxide (NO.) selectively vasodilates the pulmonary vasculature and the fact that pulmonary artery hypertension appears to play a pivotal and central role in the clinical manifestations of adult respiratory distress syndrome have led to an explosion of interest in this treatment modality. Improved pulmonary function and reduced ventilatory support have been noted in some patients with acute lung disease treated with inhaled NO.. The efficacy of inhaled NO. in various animal models has been inconsistent. Although it appears likely that inhaled NO. will be a useful adjunct in the treatment of patients with acute lung disease, the appropriate role of inhaled NO. in the treatment of ARDS remains uncertain. In order for inhaled NO. to be clinically useful in patients, this modality will have to be combined with other treatments that alter the florid inflammatory response. One should anticipate the most benefit in patients in whom respiratory failure is secondary to pressure-driven pulmonary edema and true intrapulmonary shunt.

Acute Disease↗

PubMed1995

Burn center care for patients with toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life threatening exfoliative disorder that is most commonly precipitated by the administration of a medication. Efforts to reduce morbidity and improve survival have brought into question the use of corticosteroids and recommend the transfer of patients to a burn center to facilitate wound care. STUDY DESIGN: This study evaluated the correlation of measures of disease severity and impact of treatment strategies on morbidity and mortality in patients with TEN. The records of all patients with TEN admitted to the United States Army Institute of Surgical Research during a 12 year period were reviewed. Patient characteristics, etiologic agents, time to referral of patients to the burn center, corticosteroid therapy, and other demographic features were studied. Univariate and multivariate analyses were used to determine the significance of these factors with respect to outcome. RESULTS: The sulfonamides and phenytoin were the most frequently identified etiologic agents. Patients at the extremes of age had a higher mortality rate. The period of hospitalization was longer in patients transferred to the burn center more than seven days after skin slough. Percent of epidermalysis, white blood cell count nadir, and corticosteroid administration for more than 48 hours were independently associated with mortality. CONCLUSIONS: These data indicate that the sulfonamides and phenytoin are the most common etiologic agents, expeditious transfer to a burn center reduces morbidity, and corticosteroid administration dramatically increases mortality.

Adrenal Cortex Hormones↗

PubMed1994

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.

Administration, Inhalation↗

PubMed1994

The effects of pentoxifylline on pulmonary function following smoke inhalation.

Bronchopulmonary injury secondary to smoke inhalation is a significant comorbid factor following major thermal trauma. The present study evaluates the effects of pentoxifylline (PTX) on pulmonary function in an ovine model of inhalation injury. Following smoke exposure to produce a moderate inhalation injury, 16 animals were divided into two groups. Group 1 animals (n = 8) were untreated; Group 2 animals (n = 8) were treated continuously with pentoxifylline following smoke exposure. The animals were observed in the unintubated, awake state for 48 hr. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution (VA/Q), analyzed using the multiple inert gas elimination technique, and bronchoalveolar lavage (BAL) were performed at 48 hr. The wet to dry lung weight ratio was measured following necropsy. In Group 2, the progressive hypoxemia observed following smoke inhalation was attenuated with less VA/Q mismatching than in Group 1 (P < 0.05). Pulmonary hypertension secondary to increased vascular resistance was also attenuated in Group 2 (P < 0.05). In BAL fluid, polymorphonuclear leukocytes, total protein content, and conjugated dienes were less in Group 2 than in Group 1 (P < 0.05). Plasma-conjugated diene levels were also lower in Group 2 at 48 hr. Extravascular lung water and decrease in lung compliance were greater in Group 1. There was less morphologic evidence of airway injury in Group 2 compared to Group 1. The improvement of pulmonary function following treatment with PTX suggests that this agent may be useful in the management of smoke inhalation injury.

Animals↗

PubMed1994

Predicting ventilation failure in children with inhalation injury.

Despite advances in mechanical ventilatory support for patients with smoke inhalation injury, including the use of high-frequency flow-interruption ventilators such as the VDR, inhalation injury alone may increase mortality by as much as 20% in patients with thermal injury, and up to 60% when pneumonia occurs. Inhalation injury causes a primary large and small airway epithelial insult that results in ventilation abnormalities, rather than a primary alveolar lesion that results in oxygenation abnormalities as occur in multiple-system organ failure. Patients with inhalation injury requiring high ventilatory pressures experience complications of barotrauma and frequently succumb to necrotizing tracheobronchitis and oxygenation abnormalities after 2 to 4 weeks of mechanical ventilation. Ventilatory indexes obtained early in the postburn period allow the development of accurate predictive formulae that identify patients who will not be adequately supported by mechanical ventilation after smoke inhalation injury. Early identification of such patients will allow rapid conversion to other methods of ventilatory support that effect gas exchange, with minimal risk of further barotrauma, while inhalation injury healing occurs. Such predictors may be developed for other disease processes that are characterized by severe pulmonary ventilatory dysfunction.

Adolescent↗

PubMed1994

Insulin-like growth factor-1 lowers protein oxidation in patients with thermal injury.

OBJECTIVE: The effect of insulin-like growth factor-1 (IGF-1) on energy expenditure and protein and glucose metabolism in a group of patients with thermal injury was determined. SUMMARY BACKGROUND DATA: Accelerated protein catabolism is a constant feature of the hypermetabolic response to thermal injury. Insulin-like growth factor-1 has been reported to minimize protein catabolism and normalize energy expenditure in animal models of thermal injury. METHODS: To determine the efficacy of IGF-1 in human burn patients, resting energy expenditure (metabolic cart), whole body protein kinetics (N15 Lysine), and glucose disposal (glucose tolerance test) were assessed in eight burn patients before and after a 3-day infusion of IGF-1 (20 micrograms/kg/hr). All patients were fluid-resuscitated uneventfully and were without obvious infection at the time of study. Enteral nutrition was administered at a constant rate before and during the IGF-1 infusion. RESULTS: Resting energy expenditure was not altered by IGF-1 (40.3 +/- 2.2 vs. 39.1 +/- 2.3 kcal/kg/day). However, glucose uptake was promoted, and protein oxidation decreased significantly (0.118 +/- 0.029 vs. 0.087 +/- 0.021 g/kg/d, p < 0.05) by IGF-1. In addition, insulin secretion, in response to a glucose challenge, was blunted. CONCLUSIONS: Insulin-like growth factor-1 therapy has a beneficial effect in preserving lean body mass during severe stress conditions by minimizing the flux of amino acids toward oxidation.

Adult↗

PubMed1994

Comparison of acid neutralizing and non-acid neutralizing stress ulcer prophylaxis in thermally injured patients.

We have compared the effectiveness of non-acid neutralizing stress ulcer prophylaxis (SUC) with sucralfate (n = 48) with that of acid neutralizing prophylaxis (AN) utilizing antacids and cimetidine (n = 48) in the prevention of stress ulcer bleeding and nosocomial pneumonia (PN) in thermally injured patients. In the subset of intubated patients, the incidence of PN was 17.8% and 42.8% in the AN and SUC groups, respectively (p < 0.05) despite a similar postburn time of onset of pneumonia. Ten patients in each group died. Three patients in the SUC group developed upper GI bleeding with one requiring gastrectomy. Bacterial colonization of the upper airway occurred in virtually all patients, whereas 83% (SUC) and 96% (AN) had colonization of gastric contents. Gram-negative colonization rates for the upper airway were not different (70%) whereas 48% of SUC patients compared with 60% of AN patients had gram-negative gastric colonization. In conclusion, SUC therapy was efficacious in the prevention of stress ulcer bleeding but did not alter the rate of bacterial colonization of the airway or gastric contents, and was associated with a higher incidence of nosocomial pneumonia in intubated patients.

Adult↗

PubMed1994

A longitudinal study of resting energy expenditure in thermally injured patients.

We have recently developed a new burn-specific equation that satisfactorily estimates initial caloric requirements for thermally injured patients. In the present study, we compared these estimates with resting energy expenditures (REE) (n = 141) measured weekly by indirect calorimetry in 20 patients between postburn days 3 and 348. In this group, mean initial burn size was 46.7% (range, 21-88) and mean age 31.3 years (range, 19-61). Serial measurements were continued until the burn wounds were closed or the patient was discharged. Multiple regression analysis indicated a relationship between REE, initial burn size, and postburn day in these patients (r = 0.65). This analysis indicated a general trend of decline in REE toward normal values 100 to 150 days postburn in patients with smaller burns (20%-40%) and roughly 250 days postinjury in those with larger burns (> 75%). The initial predictive equation appeared adequate for estimating caloric needs during the first postburn month, but beyond 30 days postburn indirect calorimetric measurements became necessary for accurate estimation of caloric requirements.

Adult↗

PubMed1994

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.

Administration, Inhalation↗

PubMed1994

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury.

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.

Analysis of Variance↗

PubMed1994

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.

Administration, Inhalation↗

PubMed1993

Improved survival of burned patients with inhalation injury.

OBJECTIVE: To study a cohort of patients treated at the same institution and to compare that patient population with that of a previous report documenting the comorbidity of inhalation injury and pneumonia. Specifically, we wanted to determine whether there had been an improvement in survival of patients suffering inhalation injury. DESIGN: A retrospective review. SETTING: The US Army Institute of Surgical Research, Ft Sam Houston, Tex, a 40-bed burn intensive care referral unit. SUBJECTS: One thousand two hundred fifty-six thermally injured patients treated between January 1985 and December 1990. MAIN OUTCOME MEASURE: A comparison of pneumonia frequency and ultimate survival of the current cohort of patients as compared with a previously generated stepwise logistic analysis predicting mortality on the basis of 1980 to 1984 patient data. RESULTS: Of 1256 burned patients admitted between 1985 and 1990, there were 330 identified as having inhalation injury. These patients were older (35.0 vs 26.6 years) and had more extensive burns (41.1% vs 18.3%) and a higher mortality (29.4% vs 5.0%) than did the patients without inhalation injury. When compared with a mortality predictor generated from 1980 through 1984 patient data, patients in the most recent period had a lower mortality than predicted (29.4% vs 41.4%). Patients with less severe injury (positive xenon scan, negative results of bronchoscopy; n = 85), although having a similar incidence of pneumonia (13.1% vs 19.5%) as the same group from 1980 through 1984, accounted for the most improvement in survival. The 3.6% mortality was significantly less than the predicted rate of 15.7%. Patients with positive results of bronchoscopy (n = 245) also showed some improvement in outcome from that predicted (38.3% vs 50.2%) despite no change in the rate of pneumonia (46.9% vs 48.5%). Further improvement in survival was realized in those patients supported with high-frequency ventilation. Although their age (33.9 vs 36.3 years), burn size (46.0% vs 45.5%), and duration of intubation (16.8 vs 15.1 days) were similar to those of conventionally treated patients, mortality was significantly less than predicted (16.4% vs 40.9%) and less than that in patients treated with conventional ventilation (16.4% vs 42.7%). CONCLUSIONS: The improvement in survival of patients with inhalation injury represents the aggregate effects of the general improvement and outcome of all burned patients, the prevention of pneumonia by high-frequency ventilation, and the reduced mortality from the pneumonias that did occur.

Adult↗

PubMed1993

Leukocyte responses to injury.

Injury elicits a response from all cells of the immune system in which cytokines and other metabolic products of activated leukocytes can act either beneficially to provide for enhanced host resistance or deleteriously to depress the function of remote organs and cause what has been termed systemic inflammation. These at times antithecal responses of leukocytes that appear to integrate postinjury changes in the neuroendocrine, immune, and coagulation systems have been implicated as principal causative factors in multiple systems organ failure. Numerous investigators have evaluated a variety of therapeutic agents to prevent and control infection by restoring leukocyte function, while others have evaluated antagonists and monoclonal antibodies as a means of controlling the exaggerated and persistent actions of leukocytes and cytokines caused by systemic inflammation. The redundancies of the cell populations and the cytokines and other metabolites produced by the cells predictably limit the effectiveness of any single agent and make clinical evaluation of such agents difficult.

Antibodies, Monoclonal↗

PubMed1993

Plasma cytokines after thermal injury and their relationship to infection.

OBJECTIVE: The relationship of plasma cytokine levels to infection, core temperature, and to one another in patients with thermal injury was examined. SUMMARY BACKGROUND DATA: The response to infection has been associated with cytokines such as interleukin 1 beta (IL1 beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF alpha), and these cytokines have been studied in various inflammatory diseases. The authors previously reported that patients with thermal injury have elevated IL1 beta and IL6 plasma levels and that these cytokines may play different roles in the response to thermal injury. METHODS: IL1 beta, IL6, and TNF alpha were measured by enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 27 patients. RESULTS: IL6 and TNF alpha levels were increased in severely infected patients as compared to patients who remained free of infection, and the IL6 level was higher in infected patients who died than those who survived. There was no apparent relationship between IL1 beta levels and infection. IL6 and IL1 beta were positively correlated with core temperature. The correlations between IL6 and IL1 beta, between IL6 and TNF alpha, and between TNF alpha and IL1 beta were significant. CONCLUSIONS: These results suggest that IL6 and TNF alpha play a role in the response of burned patients to infection.

Adult↗