Weaning injured patients with prolonged pulmonary failure from mechanical ventilation in a non-intensive care unit setting.

BACKGROUND: Injured patients with pulmonary failure often require prolonged length of stay in an intensive care unit (ICU), which includes weaning from ventilatory support. In the last decade, noninvasive ventilation modes have been established as safe and effective. One method for accomplishing this mode of ventilation uses a simple bilevel ventilator. Because this ventilator has been successfully used in hospital wards, we postulated that bilevel ventilators could provide sufficient support during weaning from mechanical ventilation of injured patients in a non-ICU setting. METHODS: A retrospective review of trauma patients (August 1996-January 1999) undergoing bilevel positive pressure ventilation as the final phase of weaning was conducted. Before ward transfer with bilevel ventilation, conventionally ventilated ICU patients were changed to bilevel ventilation and were required to tolerate this mode for at least 24 hours. All patients had a tracheostomy as a secure airway. Outcomes analyzed included ICU length of stay, hospital length of stay, duration of mechanical ventilation, weaning success, complications, and survival. RESULTS: Fifty-one patients (39 men, 12 women) with a mean age of 53 received more than 24 hours of bilevel positive pressure ventilation. Mean Injury Severity Score was 29, with blunt mechanisms of injury occurring in 90%. Chest or spinal cord injuries that affected pulmonary mechanics were present in 75% of patients. Ventilator-associated pneumonia was treated in 43% of patients. Mean ICU length of stay and hospital length of stay were 21 and 34 days, respectively. Weaning was successful in 89% of patients, whereas 11% were discharged to skilled nursing facilities still receiving bilevel positive pressure ventilation. Two patients died, neither from a pulmonary nor airway complication. Of the remaining 49 patients, 12 were weaned in the ICU and 37 were transferred to the ward with bilevel ventilatory support. The average length of ward ventilation was 6.5 +/- 5.4 days (n = 37). CONCLUSIONS: Implementation of a program using bilevel ventilation to support the terminal phase of weaning seriously injured patients from mechanical ventilation was successful. After initiating this mode in the ICU, it was satisfactorily continued in standard surgical wards. Because this method enabled the withdrawal of ventilatory support in a non-ICU setting, its major advantage was reducing ICU length of stay.

Transforming growth factor-beta is a potent inhibitor of extracellular matrix degradation by cultured human mesangial cells.

Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in the progression from acute glomerular injury to end-stage renal disease. Although enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation, the role of decreased ECM degradation is largely unknown. It was previously shown that glomerular ECM degradation is mediated by a plasminogen activator (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little information is available regarding the factors that regulate the activity of this degradative cascade in normal or pathologic states. Transforming growth factor-beta1 (TGF-beta1) is shown here to be a potent inhibitor of ECM degradation by cultured human mesangial cells. Using human mesangial cells grown on thin films of 125I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the presence of TGF-beta1 was observed, reaching >90% inhibition with 0.4 ng/ml TGF-beta1. Addition of anti-TGF-beta antibodies (4 microg/ml) in the absence of exogenous TGF-beta increased ECM degradation (1.8+/-0.2-fold versus controls, P<0.05). In contrast, platelet-derived growth factor, at concentrations up to 10 ng/ml, had no effect on ECM degradation. TGF-beta completely blocked the conversion of plasminogen to plasmin and markedly reduced the conversion of latent MMP-2 to active MMP-2. TGF-beta did not significantly alter the levels of tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did increase the levels of PA inhibitor- (1.8-fold, P<0.05), the major physiologic inhibitor of PA. These data document that TGF-beta is a potent inhibitor of ECM degradation by cultured human mesangial cells, and they suggest that decreased mesangial matrix degradation, caused by TGF-beta-mediated decreases in the activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix accumulation that occurs in progressive renal disease.

An increased incidence of rejection episodes. One of the causes of worse kidney transplantation survival in black recipients.

OBJECTIVE: To evaluate the cause of worse kidney allograft survival in black recipients, which has been the source of considerable interest and debate. DESIGN: Three hundred ninety-two consecutive renal allografts (O HLA mismatch grafts excluded) were reviewed. Of the recipients, 57% were black, 27% received living donor grafts, and 86% received their first transplant. All recipients underwent an oral cyclosporine induction protocol with triple drug maintenance. Crude graft survival, the risk of rejection, and the need for dialysis were determined using donor and recipient demographic and immunologic variables. RESULTS: Graft survival was 84%, 67%, and 50% at 1, 3, and 5 years after the transplantation, respectively. The survival of black recipients was 4%, 11%, and 20% worse than that of white recipients at 1, 3, and 5 years, respectively (P < .002). When only pretransplantation variables were considered, black recipient race was the only variable that predicted graft loss in the multivariate analysis (relative risk [RR] = 1.6, P = .09). When posttransplantation and pretransplantation variables were used, cadaver donor (RR = 1.7), an episode of rejection (RR = 2.6), and the need for dialysis (RR = 2.7) were independent variables that predicted graft loss (P < .001). Black recipient race was a dependent variable. Four pretransplantation variables predicted the risk of dialysis: black race (RR = 3.6), male recipient (RR = 2.1), cadaveric donor (RR = 2.2), and a peak panel-reactive antibody level greater than 30% (RR = 2.8). Three pretransplantation variables predicted the risk of rejection: black race (RR = 1.7), male recipient (RR = 1.6), and a current panel-reactive antibody level greater than 30% (RR = 5.3). CONCLUSIONS: These data suggest that black recipient race is a dependent predictor of renal allograft survival when the posttransplantation events of rejection and dialysis are considered. Black recipients have more immunologic complications after renal transplantation that result in worse graft survival. These results confirm the importance of postallograft events as the major determinants of long-term graft survival and suggest that black recipients are receiving inadequate immunosuppression. These data support attempts to tailor immunosuppressive protocols to recipient pretransplantation risk profiles as a way to improve graft survival in the high-risk recipient.

Donor race does not affect cadaver kidney transplant survival--a single center experience.

Black kidney transplant recipients have worse graft survival than white recipients. Speculation regarding etiology has focused on differences in human lymphocyte antigens (HLA). Some suggest that improvements in graft survival would be obtained if donor and recipient race were matched. We reviewed 236 cadaver transplants performed over 9 years at a single center using an HLA-match-driven allocation system and a uniform immunosuppressive protocol to determine the impact of donor race on graft survival. A multivariate analysis of graft survival using patient race, sex, age, transplant number, current and maximum plasma renin activity, donor race, cold ischemia time and HLA mismatch, the need for dialysis, and the presence of rejection as independent variables. Sixty percent of recipients were black, and 82% were primary transplants; 28 kidneys (12%) were from black donors. The 112 patients with the same race donor had identical 5-year graft survival as the 124 who had a different race donor (40%; P = 0.1726). The 5-year survival of the 88 white recipients of white donor organs was better than that of the 120 black recipients of white donor organs (54% vs. 42%, respectively; P = 0.0398). Black recipients (t1/2 = 37 months) did worse than white recipients (t1/2 = 60 months) regardless of organ source (P = 0.023). In the multivariate analysis, neither donor nor recipient race were an independent variable in predicting graft survival. Rejection (RR = 2.9) and the need for dialysis on the transplant admission (RR = 4.1) were the only factors that predicted poor survival. Black recipients had more rejection (P = 0.04) but not more need for dialysis posttransplant regardless of donor race. Donor race did not affect graft survival in this series. The effect of recipient race on graft survival was due to an increased incidence of rejection episodes in black recipients, which was independent of HLA mismatch. These data suggest that improvements in immunosuppression, not changes in allocation, are needed to improve graft survival.