RESUMO
Postsurgical handover of pediatric patients from operating rooms (OR) to pediatric intensive care units (PICU) is a critical step. This transition is susceptible to errors and inefficiencies particularly if poor multidisciplinary teamwork occurs. Despite wide adoption of standardized handover interventions, comprehensive investigations into joint effects for patient care and provider outcomes are scarce. We aimed to improve OR-PICU handovers quality and sought to evaluate the intervention with particular attention to patient care effects and provider outcomes. A prospective, before-after-study design with an interrupted-series and a multi-source, mixed-methods evaluation approach was established. Drawing upon a participative plan-do-study-act approach, a standardized, checklist-based handover process was designed and implemented. For effect assessments, we observed OR-PICU handovers on site (pre implementation: n = 31, post: n = 30), respectively, with standardized expert observation and provider self-report tools (n = 111, n = 110). Setting was a tertiary Pediatric University Hospital. Supplementary qualitative, semi-structured interviews were conducted, and a general inductive content analysis approach was used to identify key facilitators and barriers on implementation. Improvement efforts focused on stepwise implementation of (1) standardized handover process and (2) a checklist for multi-professional OR-PICU handover communication. We observed significant increases in team and patient setup (pre: 79.3%, post: 98.6%, p < .01), enhanced team engagement (pre: 50%, post: 81.7%, p < .01), and comprehensive information transfer by the anesthesia sub-team (pre: 78.6%, post: 87.3%, p < .01). Expert-rated teamwork outcomes were consistently higher, yet self-reported teamwork did not change over time. Provider perceived stress and disruptions did not change, mental workload tended to decrease over time (pre: M = 3.2, post: 2.9, p = .08). Comprehensiveness of post-operative patient information reported by PICU physician increased significantly: pre: 65.9%, post: 76.2%, p < .05. After implementation, providers acknowledged the importance of standardized handover practices and associated benefits for facilitation of information transfer and comprehensiveness. Among reported barriers were obstacles during implementation as well as insufficient consideration of professionals' individual workflow after surgery. CONCLUSION: A multidisciplinary intervention for postsurgical pediatric patient handovers was associated with improved expert-rated teamwork and fewer omissions of key patient information over time. Inconsistent results were obtained for provider-rated mental workload and teamwork outcomes. The findings contribute to a better understanding concerning the interplay of teamwork and provider cognitions in the course of establishing safe patient transitions in pediatric care. WHAT IS KNOWN: ⢠Transfer of critically ill children conveys significant challenges for interprofessional communication and teamwork. Prospective research into interventions for safe and efficient handover practices of OR PICU patient transitions is necessary. ⢠Checklists are assumed to facilitate cognitive load among providers in acute clinical environments. WHAT IS NEW: ⢠A standardized, checklist-based handover intervention was associated with improvements in team set-up and information transfer. Provider outcomes such as mental workload and stress did not change over time. ⢠The combination of teamwork and provider assessments allows a more nuanced understanding of implementation barriers and sustainable effects in course of OR-PICU handover interventions.
Assuntos
Transferência da Responsabilidade pelo Paciente , Humanos , Criança , Transferência de Pacientes , Salas Cirúrgicas , Estudos Prospectivos , Unidades de Terapia Intensiva PediátricaRESUMO
STUDY OBJECTIVE: Synthetic colloids are used for perioperative fluid management. We hypothesized that their use may be associated with changes in major histocompatibility complex (MHC) class II expression. This could affect patients' morbidity and mortality during clinical intervention. SETTING: University research laboratory. SUBJECTS: Whole blood samples from healthy volunteers. INTERVENTIONS: Whole blood samples from healthy volunteers (n = 6) were incubated with different concentrations of hydroxyethyl starch (HES) from maize and potato (pHES), dextran, and polygelin (gelatine) for 24 hours with or without 100 U/mL human interferon gamma (IFN-gamma; stimulus for MHC class II expression). The expression of human leukocyte antigen (HLA): HLA-DR, HLA-DQ, and HLA-DP was detected simultaneously by a fluoresceinisothiocyanate (FITC)-labeled antibody and analyzed by flow cytometry on lymphocytes and monocytes. MEASUREMENTS AND MAIN RESULTS: Hydroxyethyl starch, pHES, and dextran induced a significant increase in HLA expression. The induction of MHC class II was independent of the structure (50 mg/mL: control, 8.7+/-1.4%; HES, 28 +/- 9.7%; pHES, 29.8 +/- 11.7%; and dextran, 50.2 +/- 8.1%). In contrast, polygelin increased HLA expression only at the highest concentration of gelatine (5 mg/mL, 7.8 +/- 1%; 50 mg/mL, 7.6 +/- 0.8%; 100 mg/mL, 7.3 +/- 1%; 200 mg/mL,16.2 +/- 2.3%). The addition of IFN-gamma decreased HLA expression in presence of highest concentration of HES and dextran. CONCLUSION: In an ex vivo laboratory setting, we demonstrate that high concentrations of plasma expanders are associated with increased HLA expression on lymphocytes and monocytes. However, further in vivo studies are necessary to demonstrate the clinical significance of this observation.
Assuntos
Coloides/farmacologia , Genes MHC da Classe II/genética , Dextranos/farmacologia , Relação Dose-Resposta a Droga , Citometria de Fluxo , Imunofluorescência , Gelatina/farmacologia , Expressão Gênica/efeitos dos fármacos , Antígenos HLA/biossíntese , Humanos , Derivados de Hidroxietil Amido/farmacologia , Técnicas In Vitro , Interferon gama/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pressão Osmótica , Substitutos do Plasma/farmacologia , Proteínas Recombinantes , Albumina Sérica/metabolismo , Estimulação QuímicaRESUMO
BACKGROUND: It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions. METHODS: Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils. RESULTS: Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins. CONCLUSIONS: This study shows that synthetic colloids inhibit neutrophil adhesion by a neutrophil-dependent mechanism rather than interfering with endothelial cell activation. This suggests that inhibition of leukocyte sequestration by volume support is a common and transient phenomenon depending on the colloid concentration in plasma.
Assuntos
Comunicação Celular/efeitos dos fármacos , Coloides/farmacologia , Células Endoteliais/efeitos dos fármacos , Integrinas/antagonistas & inibidores , Neutrófilos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Selectina E/sangue , Células Endoteliais/fisiologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Neutrófilos/fisiologia , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Respiratory syncytial virus (RSV) is the major etiologic agent of severe epidemic lower respiratory tract infections in infancy. Airway mucosal inflammation plays a critical role in the pathogenesis of RSV disease in both natural and experimental infections. RSV is among the most potent biological stimuli that induce the expression of inflammatory genes, including those encoding chemokines, but the mechanism(s) that controls virus-mediated airway inflammation in vivo has not been fully elucidated. Herein we show that the inoculation of BALB/c mice with RSV results in rapid activation of the multisubunit IkappaB kinase (IKK) in lung tissue. IKK transduces upstream activating signals into the rate-limiting phosphorylation (and proteolytic degradation) of IkappaBalpha, the inhibitory subunit that under normal conditions binds to the nuclear factor (NF)-kappaB complex and keeps it in an inactive cytoplasmic form. Mice treated intranasally with interleukin-10 or with a specific cell-permeable peptide that blocks the association of the catalytic subunit IKKbeta with the regulatory protein NEMO showed a striking reduction of lung NF-kappaB DNA binding activity, chemokine gene expression, and airway inflammation in response to RSV infection. These findings suggest that IKKbeta may be a potential target for the treatment of acute or chronic inflammatory diseases of the lung.
Assuntos
Quimiocinas/biossíntese , Pneumonia/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/patologia , Animais , Lavagem Broncoalveolar , Linhagem Celular Tumoral , Quimiocina CCL2/biossíntese , Quimiocina CCL2/genética , Quimiocina CCL4 , Quimiocina CCL5/biossíntese , Quimiocina CCL5/genética , Quimiocinas/genética , Feminino , Humanos , Quinase I-kappa B , Interleucina-10/farmacologia , Pulmão/metabolismo , Pulmão/virologia , Proteínas Inflamatórias de Macrófagos/biossíntese , Proteínas Inflamatórias de Macrófagos/genética , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Peptídeos/farmacologia , Pneumonia/enzimologia , Pneumonia/patologia , Pneumonia/virologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Infecções por Vírus Respiratório Sincicial/enzimologia , Vírus Sinciciais Respiratórios/fisiologia , Replicação ViralRESUMO
BACKGROUND: In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements. METHODS: Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC. RESULTS: Peak levels in plasma amounted to 39.5 +/- 10.5 mg/l (mean +/- SD) and trough levels were 2.4 +/- 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 +/- 0.77 h. The sieving coefficient of meropenem was 0.91 +/- 0.10 and the recovery in hemofiltrate amounted to 30.9 +/- 11.5% of the dose. CONCLUSIONS: A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.
Assuntos
Injúria Renal Aguda/terapia , Hemofiltração , Tienamicinas/farmacologia , Tienamicinas/farmacocinética , Injúria Renal Aguda/complicações , Idoso , Infecções Bacterianas/tratamento farmacológico , Estado Terminal , Esquema de Medicação , Feminino , Meia-Vida , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
STUDY OBJECTIVE: To determine the applicability and reliability of a screening questionnaire to detect patients at high-risk of latex allergy; to assess the importance of other allergies such as profilin allergies (pollinosis) for presence of latex sensitization; and to determine the clinical effectiveness of preemptive avoidance of latex exposure in high-risk patients. DESIGN: Prospective, clinical trial. SETTING: Operative theater of a university hospital. PATIENTS: 95 adult patients. INTERVENTIONS: Patients were preoperatively screened and classified for present latex allergy (high-risk and low-risk group) according to a specially designed screening questionnaire. Anesthesia and surgery in the high-risk group were performed strictly avoiding latex-containing materials. The low-risk group (other allergies including pollinosis) received routine treatment, without latex-avoidance. Effects of latex avoidance or exposure were evaluated by measuring specific IgE titers perioperatively. MEASUREMENTS AND MAIN RESULTS: According to the questionnaire, 45 patients at high risk were defined. Validity of classification of high-risk patients is supported by significantly higher total IgE and latex and grass profilin specific IgE compared to the low-risk group. There were no significant differences in other profilin-specific IgEs. In one case of severe anaphylactic reaction a drop of latex-specific IgE during surgery could be observed. CONCLUSION: The questionnaire allowed the identification of most patients at high risk for latex allergy. In isolated pollinosis no changes in any specific IgE levels were detectable. Strict avoidance of perioperative latex exposure in high-risk patients increases safety during anesthesia and surgery.
Assuntos
Anestesia , Hipersensibilidade ao Látex/diagnóstico , Sequência de Aminoácidos , Reações Cruzadas , Doença Ambiental/diagnóstico , Feminino , Humanos , Imunoglobulina E/análise , Imunoglobulina E/biossíntese , Látex/química , Hipersensibilidade ao Látex/prevenção & controle , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Poaceae/química , Pólen/química , Pólen/imunologia , Cuidados Pré-Operatórios , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Inquéritos e QuestionáriosRESUMO
UNLABELLED: Leukocyte adhesion to endothelial cells contributes to microcirculatory disturbances during severe shock syndromes. Whereas certain plasma expanders inhibit leukocyte adhesion, contaminants of plasma protein solutions upregulate endothelial cell adhesion molecules in certain cases. We performed this study to determine whether fresh frozen plasma (FFP) affects neutrophil-endothelial interactions in cocultures of neutrophils and human umbilical vein endothelial cells (HUVEC) in vitro. HUVEC (n = 9) were incubated with either 20% FFP or 20% serum in medium for 6 h. Expression of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule-1 was induced by tumor necrosis factor alpha (0.5 ng/mL for 4 h) and measured by flow cytometry. Neutrophil adhesion was examined in a parallel plate flow chamber in which isolated neutrophils were perfused over pretreated HUVEC under postcapillary flow conditions. Incubation with FFP decreased E-selectin and intercellular adhesion molecule 1 on activated HUVEC by 28% and 22%, respectively (P < or = 0.01; analysis of covariance). Consequently, neutrophil adhesion decreased by 20%-41% in FFP-treated cocultures (n = 4; P < or = 0.01; paired Student's t-test). We conclude that FFP attenuates the inflammatory response of endothelial cells with regard to neutrophil-endothelial interactions. Because the composition of patients' plasma is affected not only by transfusion, but more frequently by shock treatment with IV fluids, plasma dilution in critically ill patients could be important. IMPLICATIONS: During shock, fluid administration leads to a massive dilution of plasma. Apart from maintaining hemodynamics, this might affect tissue damage by influencing leukocyte accumulation in the microvasculature. Using endothelial cells, isolated neutrophils, and a parallel plate flow chamber, we studied the effects of fresh frozen plasma on neutrophil-endothelial interactions.
Assuntos
Endotélio Vascular/fisiologia , Neutrófilos/fisiologia , Plasma/fisiologia , Anticorpos Monoclonais/farmacologia , Moléculas de Adesão Celular/fisiologia , Selectina E/metabolismo , Endotélio Vascular/citologia , Humanos , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/metabolismo , Cordão Umbilical/citologia , Vênulas/citologiaRESUMO
Monocyte adhesion contributes to perfusion abnormalities, tissue damage, and activation of the coagulation system seen during trauma, shock, or overwhelming inflammation. This study was performed to determine whether an intravenous fish oil emulsion used for parenteral nutrition attenuates monocyte-endothelial interactions under flow and reduces procoagulant activity, measured as tissue factor (TF) expression on adherent monocytes in vitro. Endothelial cell monolayers were incubated with either an intravenous fish oil emulsion or a conventional omega-6 lipid emulsion at 0.05 to 1 mg/ml for 24 h. Six hours following activation with TNFalpha (25 ng/ml), expression of endothelial cell adhesion molecules was measured by flow cytometry. Adhesion of isolated monocytes to pretreated endothelium was examined in a parallel plate flow chamber at a shear stress of 1.5 dynes/cm2. Following perfusion, the cells were cocultured for an additional 4 h and TF expression on monocytes was determined by flow cytometry. In contrast to omega-6 lipids, fish oil down-regulated E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in a dose-dependent manner. P-selectin, however, remained unchanged. In addition, firm adhesion was reduced to 54%, whereas rolling interactions remained unchanged. Fish oil exhibited no effect on the TF expression on cocultured monocytes. We conclude that intravenous fish oil emulsions reduce both endothelial cell adhesion molecule expression and monocyte adhesion. However, under postcapillary flow conditions, rolling interactions via P-selectin remain unaltered. The functional importance of this effect is illustrated by the corresponding upregulation of TF in response to residual monocyte-endothelial interactions.
Assuntos
Emulsões/farmacologia , Endotélio/citologia , Endotélio/efeitos dos fármacos , Óleos de Peixe/farmacologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Nutrição Parenteral , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Técnicas de Cocultura , Citocinas/farmacologia , Endotélio/metabolismo , Humanos , Monócitos/metabolismo , Tromboplastina/metabolismoRESUMO
The transcription factor nuclear factor (NF)-kappaB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-kappaB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-kappaB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-kappaB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.
Assuntos
Proteínas de Drosophila , Pulmão/virologia , Macrófagos Alveolares/fisiologia , Glicoproteínas de Membrana/fisiologia , NF-kappa B/metabolismo , Receptores de Superfície Celular/fisiologia , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Vírus Sinciciais Respiratórios/fisiologia , Animais , Humanos , Pulmão/metabolismo , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Subunidades Proteicas , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/genética , Receptor 4 Toll-Like , Receptores Toll-LikeRESUMO
Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-kappa B. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1 alpha, MIP-1 beta, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-kappa B activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.