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Biomedical subjects

W G Cioffi

Publications and source records attributed to W G Cioffi.

At least 109 records · Page 6Linked to original sources

Decreased pulmonary damage in primates with inhalation injury treated with high-frequency ventilation.

OBJECTIVE: This study compared two forms of high-frequency ventilation (HFV) with conventional volume ventilation (CON) in a primate model of inhalation injury to determine whether ventilatory mode was a determinant of pulmonary damage. SUMMARY BACKGROUND DATA: The authors previously reported that the prophylactic use of high-frequency flow interruption in patients with bronchoscopically diagnosed inhalation injury requiring mechanical ventilatory support resulted in a significant decrement in mortality. They hypothesized that a reduction in ventilatory mode induced pulmonary damage was in part responsible for their clinical results. METHODS: Fifteen adult baboons were randomized to one of three ventilatory modes (CON, high-frequency flow interruption [HFFI], or high-frequency oscillatory ventilation [HFO]) after moderate smoke injury. Ventilatory support was tailored to the same physiologic endpoints. After 7 days, the animals were killed and pulmonary pathologic changes were scored and compared. Repetitive physiologic and biochemical data were compared using analysis of variance for repeated measures. RESULTS: Physiologic endpoints were achieved in CON and HFFI, but not in HFO. Hemodynamic variables did not differ between CON and HFFI. The barotrauma index was greater in CON compared to HFFI (p < 0.05), despite similar PO2, FIO2, AA gradient, and PCO2. Animals treated with HFFI had significantly less parenchymal damage than those treated with CON (p = 0.03) or HFO (p = 0.0008). CONCLUSIONS: The prophylactic use of HFFI led to a significant decrement in ventilatory mode induced pulmonary damage and offers an explanation for the decreased mortality in inhalation injury patients treated with HFFI.

Animals↗

The renal effects of low-dose dopamine in thermally injured patients.

The renal effects of low-dose dopamine (LDD) therapy in hyperdynamic thermally injured patients are unknown. We investigated the renal effects of LDD in ten burn patients (mean +/- SEM age and % total body surface burned: 30.2 +/- 3.3 years and 53.4% +/- 7%) and six controls (mean age; 20.2 +/- 0.5 years). Administration of LDD significantly increased glomerular filtration rate, effective renal plasma flow, sodium excretion, and urine flow in the controls and effective renal plasma flow, urine flow, heart rate, and cardiac index in the patients. The chronotropic effect of dopamine appears to be a principal contributor to the patients' increased effective renal plasma flow. Sodium excretion was increased by LDD only in the patients in whom the predopamine sodium excretion exceeded 5 mEq/h. Lack of a consistent natriuretic effect and the consistent chronotropic effect suggest that the routine use of low-dose dopamine in burn patients is unwarranted. The side effects that attend the desired response determine clinical use, i.e., the potential for blood flow redistribution and increased cardiac work demands must be balanced against increased renal plasma flow and natriuresis.

Adult↗

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.

Adult↗

Superior mesenteric artery syndrome in a burn patient.

Weight loss resulting from the hypermetabolic response to burn injury is not unusual and is often unavoidable. The loss of retroperitoneal fat has been postulated as a major factor in the cause of the uncommon complication of superior mesenteric artery syndrome. This syndrome is frequently treated nonoperatively with aggressive nutrition support. Nasojejunal feeding past the point of obstruction should be considered as the primary method of nutrition support. Alternatively, total parenteral nutrition or a combination of enteral and parenteral feeding may be necessary to meet nutritional needs until the duodenal obstruction resolves. This case study describes the nutrition management of a burn patient who developed superior mesenteric artery syndrome.

Burns↗

Wound closure and outcome in extensively burned patients treated with cultured autologous keratinocytes.

Cultured autologous keratinocytes (CAK) have been heralded as a means to achieve more rapid closure of massive burn wounds. Despite the claimed benefits of this technology, we have failed to identify its positive impact on wound closure in extensively burned patients. Sixteen patients with a mean age of 29.7 years (range, 10-56 years) and a mean total body surface area burn of 68.2% (range, 42%-85%) underwent 22 applications of CAK supplied by a private laboratory. The keratinocyte grafts were applied to a mean of 15.9% of the body surface area (range, 4%-59%) at an average cost per patient of $43,705 (range, $9,800 to $161,000). The mean body surface area of definitive wound coverage by these grafts was 4.7% (range, 0%-18.6%). The mean length of hospitalization was 132 days (range, 50-275 days). The observed mortality was 12.5% (two patients). Our experience with this wound care approach has been assessed with respect to the extent of burn, the level of wound excision, and the site of CAK application.

Adolescent↗

Alterations in intestinal permeability after thermal injury.

Alterations in intestinal permeability have been postulated to occur after thermal injury. We evaluated the status of intestinal permeability during the first 2 postburn weeks in 15 subjects by measuring the differential excretion of enterally administered lactulose and mannitol. The mean age and burn size of the patients were 32.7 +/- 3.6 years and 53.3% +/- 5.1% of the total body surface area, respectively. Ten healthy volunteers were also studied. The lactulose-mannitol excretion ratio was 0.159 +/- 0.017 for the patients and 0.017 +/- 0.003 for controls. The increased ratio did not correlate with burn size or postburn day. Patients who developed significant clinical infections during their first 2 postburn weeks had lactulose-mannitol ratios on postburn day 2 that were significantly higher than those of controls and patients who did not develop infections. This suggests a relationship between susceptibility to infection and early alterations in intestinal permeability.

Adult↗

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.

Adult↗

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.

Burns↗

Resting energy expenditure in patients with thermal injuries.

Resting energy expenditures (REE) were measured using indirect calorimetric techniques in 62 patients with burn injuries admitted during 1987 to 1989 and compared with similar measurements made during 1972 to 1973. Energy requirements were related to burn size in both populations, but were greater in the earlier population. In the present study, data from some patients were obtained using a canopy system and from others during mechanical ventilation and were analyzed separately. The regression of REE on burn size was linear for the canopy measurements (r = 0.724) and for the ventilator measurements (r = 0.579). REE data were corrected for the expected basal metabolic rate (BMR) for each patient, with appropriate adjustment for age and sex. The regression of REE per BMR on burn size was linear (r = 0.724), differing from the curvilinear relationship found during 1972 to 1973. These data suggest a change in postburn energy requirements, probably related to differences in patient management. Predictive equations based on older data can be expected to overestimate energy requirements in patients receiving modern burn therapy.

Adolescent↗

Multidisciplinary protocol for determining aminoglycoside dosage.

A protocol for determining optimal dosages of aminoglycosides early in therapy is described, and the effectiveness of the protocol is evaluated. The protocol was developed jointly by physicians and pharmacists at a 550-bed hospital to ensure that surgical patients prescribed aminoglycosides were quickly and consistently put on a safe and effective course of therapy. Physicians select an aminoglycoside and calculate a loading dose and initial maintenance dosage by using a nomogram printed on an antimicrobial order form. Nurses are trained to administer and document aminoglycoside doses accurately and to draw blood samples at the correct times. Pharmacists order serum aminoglycoside concentration assays, analyze the results, and recommend changes in dosage when necessary. To evaluate the effectiveness of the dosing protocol, the records of surgical patients treated before and after the protocol was in place were reviewed. Compared with the control group, a higher percentage of patients treated under the protocol were receiving therapeutic, nontoxic dosages of aminoglycosides within 48 hours of the start of therapy. In addition, fewer serum drug concentration tests were ordered per patient under the protocol, and the percentage of concentration determinations useful for analysis was higher. The mean duration of aminoglycoside therapy was identical before and after the protocol was instituted, and nephrotoxic reactions tended to be less common among the protocol patients. An aminoglycoside dosing protocol requiring the cooperation of pharmacists, nurses, and physicians provides a consistent, safe, and effective means of managing aminoglycoside therapy for the hospitalized patient.

Adult↗

Fungal burn wound infection. A 10-year experience.

To evaluate our experience with fungal burn wound infection, we performed a 10-year review for comparison with our experience with bacterial burn wound infection. During the study period, a marked decline occurred in bacterial wound infection but not in fungal wound infection. Patients with either bacterial or fungal burn wound infection had massive injury, with burn size averaging greater than 50% of the total body surface area. Factors that appear to have markedly reduced bacterial burn wound infection, including patient isolation, topical chemotherapeutic agents, and burn wound excision, do not appear to have had a similar effect on fungal wound infection. The mechanism of spread and colonization of fungi, and the lack of effective topical chemotherapeutic antifungal agents, may explain in part our findings.

Adult↗

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.

Acridines↗

Prophylactic use of high-frequency percussive ventilation in patients with inhalation injury.

Death and the incidence of pneumonia are significantly increased in burn patients with inhalation injury, despite application of conventional ventilatory support techniques. The effect of high-frequency percussive ventilation on mortality rate, incidence of pulmonary infection, and barotrauma were studied in 54 burn patients with documented inhalation injury admitted between March 1987 and September 1990 as compared to an historic cohort treated between 1980 and 1984. All patients satisfied clinical criteria for mechanical ventilation. High-frequency percussive ventilation was initiated within 24 hours of intubation. The patients' mean age and burn size were 32.2 years and 47.8%, respectively (ranges, 15 to 88 years; 0% to 90%). The mean number of ventilator days was 15.3 +/- 16.7 (range, 1 to 150 days), with 26% of patients ventilated for more than 2 weeks. Fourteen patients (25.9%) developed pneumonia compared to an historic frequency of 45.8% (p less than 0.005). Mortality rate was 18.5% (10 patients) with an expected historic number of deaths of 23 (95% confidence limits of 17 to 28 deaths). The documented improvement in survival rate and decrease in the incidence of pneumonia in patients treated with prophylactic high-frequency ventilation (HFV), as compared to a cohort of patients treated in the 7 years before the trial, indicates the importance of small airway patency in the pathogenesis of inhalation injury sequelae and supports further use and evaluation of HFV.

Adolescent↗

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.

Adrenocorticotropic Hormone↗

Resuscitation of thermally injured patients.

The continued investigation and ultimate understanding of the pathophysiologic response to thermal injury and resuscitation will potentially open new avenues of fluid management. The ultimate goal of any resuscitation regimen is the preservation of organ perfusion and function. Assurance of a smooth and adequate burn resuscitation in combination with advances in wound care and coverage, inhalation injury management, and nutritional support will continue to improve the outcome of the thermally injured patient.

Burns↗

Diagnosis and treatment of inhalation injuries.

Inhalation injury continues to be a major co-morbid factor in the thermally injured patient. Appreciation of the pathophysiology of inhalation injury has been gradually acquired through active basic science and clinical research. This understanding has led to improvements in diagnosis, ventilatory support, and infection control, all of which have contributed to the improved prognosis of burn patients. As our understanding of inhalation injury continues to develop, further avenues of therapeutic investigation will arise and continue to lead to further improvement in the prognosis of thermally injured patients.

Burns, Inhalation↗

Evaluation and management of patients with inhalation injury.

Inhalation injury, present in approximately one third of burned patients treated at burn centers, increases mortality by a maximum of 20% in relation to age and extent of burn. The development of animal models of inhalation injury has made possible the identification of both the airway and vascular responses evoked by smoke inhalation. Inflammatory occlusion of terminal bronchioles and necrosis of the endobronchial mucosa render the airway and pulmonary parenchyma susceptible to infection and the resulting pneumonitis further increases mortality. Early diagnosis, best achieved by endoscopic bronchoscopy and 133xeon ventilation perfusion scan, permits timely application of high-frequency ventilation that appears to reduce the incidence of pneumonia and to decrease mortality. Pharmacologic agents give promise of ameliorating the deleterious changes of the vasculature. The recent advances in understanding inhalation injury have identified the research needed to further improve patient salvage.

Animals↗

High-frequency percussive ventilation in patients with inhalation injury.

Inhalation injury complicated by bacterial pneumonia is now one of the primary causes of morbidity and mortality in patients with thermal injury. We have investigated the use of high-frequency percussive ventilation (HFPV) as a means of ventilatory support for these patients. We propose that high-frequency ventilation may decrease the incidence of pulmonary infection following inhalation injury and decrease the incidence of iatrogenic barotrauma caused by conventional ventilation. High-frequency ventilation was instituted initially as salvage therapy in a group of five patients. In each case, normocapnia or arterial pO2 saturation of greater than 90% on a FIO2 of 60% or less was achieved with high-frequency ventilation but not with conventional ventilation. A second group of ten patients was prospectively entered into a study on the use of HFPV in patients with inhalation injury. One patient was removed from the study, and one patient was unable to be ventilated because of severely noncompliant lungs. Eight patients with a mean age of 29 years and a mean burn size of 38% of the total body surface completed the protocol. All patients survived, two developed pneumonia, and one developed subcutaneous emphysema. These results suggest that HFPV is effective in the treatment of patients with severe inhalation injury.

Adult↗