Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications.

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.

The strength of cell-mediated xenograft rejection in the mouse is due to the CD4+ indirect response.

Previous studies have shown that CD4+ T cells are responsible for the great strength of cell-mediated xenograft rejection in the mouse. In vitro studies have suggested that this CD4+ response is to xenogeneic antigens that are presented indirectly. The present studies were carried out in order to determine whether the strength of cell-mediated xenograft rejection in vivo is dependent on the CD4+ indirect response. We grafted pig skin onto mice that express class II MHC antigens only on their thymic epithelial cells (II-4+ mice). These mice have normal numbers of functional peripheral CD4+ T cells; however they lack class II MHC expression on their antigen presenting cells and are thus incapable of mounting a CD4+ T cell-mediated indirect response. Xenograft survival was prolonged on these mice. Furthermore, administration of cyclosporine and anti-CD8 monoclonal antibodies to II-4+ recipients prolonged xenograft survival to at least the same extent as allograft survival, demonstrating that the strength of cell-mediated xenograft rejection resides in the CD4+ indirect response. Despite the increased survival time, xenograft rejection still occurred in the absence of the indirect pathway. Depletion of the II-4+ recipients of their CD4+ T cell population prolonged xenograft survival even further, suggesting the presence of a weaker CD4+ direct mechanism which was virtually undetectable in vitro.

Studies of transplantation immunology with major histocompatibility complex knockout mice.

Mice deficient in the expression of either class I or class II major histocompatibility complex (MHC) antigens have been generated by use of the technique of gene disruption by homologous recombination. These animals have subsequently been mated to generate mice that are deficient in the expression of both classes of MHC antigens. Class I MHC-deficient animals have a greater than 90% reduction in cell surface expression of MHC I molecules; however, they do express low levels of class I heavy chains on their cells. Furthermore, class I-deficient mice have very few CD8S+R T cells. Class II MHC-deficient animals have no detectable expression of class II MHC molecules and a reduction in the CD4+ T cell population. Mice deficient in both MHC antigens share the characteristics of the two founder animals: low levels of class I heavy chain expression, no detectable class II expression and reduced levels of CD4+ and CD8+ T cells. Allotransplantation experiments with these animals have suggested that different mechanisms of graft rejection predominate depending on the target organ and have provided evidence for the role of the indirect pathway of antigen recognition in graft rejection. Xenotransplantation experiments involving these animals have revealed that donor MHC deficiency offers no protection to the graft, suggesting that strategies to eliminate MHC antigen expression will not be successful in generating "universal donors."