Optimizing Recognition and Management of Patients at Risk for Infection-Related Decompensation Through Team-Based Decision Making.

INTRODUCTION: Pediatric sepsis is a leading cause of death among children. Electronic alert systems may improve early recognition but do not consistently result in timely interventions given the multitude of clinical presentations, lack of treatment consensus, standardized order sets, and inadequate interdisciplinary team-based communication. We conducted a quality improvement project to improve timely critical treatment of patients at risk for infection-related decompensation (IRD) through team-based communication and standardized treatment workflow. METHODS: We evaluated children at risk for IRD as evidenced by the activation of an electronic alert system (Children at High Risk Alert Tool [CAHR-AT]) in the emergency department. Outcomes were assessed after multiple improvements including CAHR-AT implementation, clinical coassessment, visual cues for situational awareness, huddles, and standardized order sets. RESULTS: With visual cue activation, initial huddle compliance increased from 7.8% to 65.3% ( p < .001). Children receiving antibiotics by 3 hours postactivation increased from 37.9% pre-CAHR-AT to 50.7% posthuddle implementation ( p < .0001); patients who received a fluid bolus by 3 hours post-CAHR activation increased from 49.0% to 55.2% ( p = .001). CONCLUSIONS: Implementing a well-validated electronic alert tool did not improve quality measures of timely treatment for high-risk patients until combined with team-based communication, standardized reassessment, and treatment workflow.

Cost analysis and provider satisfaction with pediatrician in triage.

OBJECTIVES: The goals of this study were to (1) conduct a cost-benefit analysis, from a hospital's perspective, of using a pediatrician in triage (PIT) in the emergency department (ED) and (2) assess the impact of a physician in triage on provider satisfaction. METHODS: This was a prospective, controlled trial of PIT (intervention) versus conventional registered nurse-driven triage (control), at an urban, academic, tertiary level pediatric ED, which led to a cost-benefit analysis by looking at the effect that PIT has on length of stay (LOS) and thus on ED revenue. Provider satisfaction was assessed through surveys. RESULTS: During the 8-week study period, a total of 6579 patients were triaged: 3242 in the PIT group and 3337 in the control group. The 2 groups were similar in age, sex, admission rate, left-without-being-seen rate, and level of acuity. The mean LOS in the PIT group was 24.3 minutes shorter than in the control group. The costs of PIT seem to be increased and are not offset by savings; the net margin (total revenue minus costs) was $42,883 per year lower in the PIT than in the control group. Sensitivity analysis showed that if the LOS were reduced by more than 98.4 minutes, the cost savings would favor PIT. Most of the physicians and nurses (67%) reported that PIT facilitated their job. CONCLUSIONS: Placement of a PIT during periods of peak census resulted in shorter stay and notable provider satisfaction but at an incremental cost of $42,883 per year.

Leveraging a Safety Event Management System to Improve Organizational Learning and Safety Culture.

BACKGROUND AND OBJECTIVES: Safety event management systems (SEMS) are rich sources of patient safety information, which can be used to improve organizational safety culture. An ideal SEMS can accomplish this when the system is improved with the intention of increasing learning and engagement across the organization. To support a global aim of improving overall patient safety and becoming a highly reliable learning health system, focus was directed toward increasing event review and follow-up completion and using this information to drive resource allocation and improvement efforts. METHODS: A new integrated SEMS was customized, tested, and implemented based on identified organizational need. Revised policies were developed to define expectations for event review and follow-up. The new SEMS incorporated a closed-loop communication process which ensured information from events was shared with the event submitters and facilitated shared learning. The expected impacts, improved event reporting, and follow-up were studied and guided ongoing improvements. RESULTS: After transitioning to a new SEMS, we experienced increased overall reporting by 8.6% and improved event follow-up, demonstrated by documentation on specified system forms, by 53.7%. CONCLUSIONS: By implementing a new, efficient, and standardized SEMS, which decentralized event management processes, the organization saw increased reporting and better engagement with patient safety event review and follow-up. Overall, these results demonstrated a stronger reporting culture, which allowed for local problem solving and improved learning from every event reported. A robust reporting culture positively impacted the overall organizational culture of safety.

Identifying children at high risk for infection-related decompensation using a predictive emergency department-based electronic assessment tool.

OBJECTIVES: Electronic alert systems to identify potential sepsis in children presenting to the emergency department (ED) often either alert too frequently or fail to detect earlier stages of decompensation where timely treatment might prevent serious outcomes. METHODS: We created a predictive tool that continuously monitors our hospital's electronic health record during ED visits. The tool incorporates new standards for normal/abnormal vital signs based on data from ∼1.2 million children at 169 hospitals. Eighty-two gold standard (GS) sepsis cases arising within 48 h were identified through retrospective chart review of cases sampled from 35,586 ED visits during 2012 and 2014-2015. An additional 1,027 cases with high severity of illness (SOI) based on 3 M's All Patient Refined - Diagnosis-Related Groups (APR-DRG) were identified from these and 26,026 additional visits during 2017. An iterative process assigned weights to main factors and interactions significantly associated with GS cases, creating an overall "score" that maximized the sensitivity for GS cases and positive predictive value for high SOI outcomes. RESULTS: Tool implementation began August 2017; subsequent improvements resulted in 77% sensitivity for identifying GS sepsis within 48 h, 22.5% positive predictive value for major/extreme SOI outcomes, and 2% overall firing rate of ED patients. The incidence of high-severity outcomes increased rapidly with tool score. Admitted alert positive patients were hospitalized nearly twice as long as alert negative patients. CONCLUSIONS: Our ED-based electronic tool combines high sensitivity in predicting GS sepsis, high predictive value for physiologic decompensation, and a low firing rate. The tool can help optimize critical treatments for these high-risk children.

Implementation of an Intrahospital Transport Checklist for Emergency Department Admissions to Intensive Care.

INTRODUCTION: Intrahospital transports (IHTs) are high-risk activities with the potential for adverse outcomes. Suboptimal care of a patient in our emergency department (ED) needing IHT to the pediatric intensive care unit (ICU) identified improvement opportunities. We describe implementing a novel checklist (Briefing ED-to-ICU Transport To Exit Ready: BETTER) for improving the IHT safety of pediatric ED patients admitted to the pediatric ICU. METHODS: A multidisciplinary team used the Model for Improvement to create a key driver diagram and process map. An evidence-based IHT checklist was implemented on July 23, 2019 after multiple plan-do-study-act checklist revisions. The specific aim was a ≥80% checklist completion rate for 6 months and maintaining that rate for 6 months. An anonymous, voluntary survey of ED nurses and physicians, 9 months postimplementation, evaluated perceived improvements in IHT safety. The outcome measure was the proportion of IHT-related incident reports, per ED-to-pediatric ICU admission, comparing baseline (2-year preimplementation) and intervention (1-year postimplementation) periods. Balancing measures included a quantitative assessment for any throughput measure delays and a survey question on perceived delays. RESULTS: From July 23, 2019 to July 22, 2020, 335 (84%) of 400 ED-to-ICU admissions had completed IHT checklists. Ninety percent of survey respondents (84% response rate) agreed that the checklist improved IHT safety. The incident report rate was lower in the intervention period (0.5% versus 2.3%; P = 0.03), with special cause improvement on T-chart analysis. Balancing measures did not indicate any delays secondary to checklist implementation. CONCLUSIONS: This IHT checklist was feasible and associated with improvements in perceived safety and incident event reporting. Further studies are needed to assess generalizability.

Improving Equity of Care for Patients with Limited English Proficiency Using Quality Improvement Methodology.

Disparate clinical outcomes have been reported for patients with Limited English Proficiency (LEP) in the emergency department setting, including increased length of stay, diagnostic error rates, readmission rates, and dissatisfaction. Our emergency department had no standard processes for LEP patient identification or interpreter encounter documentation and a higher rate of 48-hour LEP return visits (RV) than English proficient patients. The aim was to eliminate gaps by increasing appropriate interpreter use and documentation (AIUD) for Spanish-speaking LEP (LEP-SS) patients from 35.7% baseline (10/17-05/18) to 100% by October 2020. METHODS: LEP-SS patient data were reviewed in the electronic medical record to determine the AIUD and RV rates. Using the Model for Improvement and multiple Plan-Do-Study-Act (PDSA) cycles, a multi-disciplinary team encouraged stakeholder engagement and identified improvement opportunities, implemented an electronic tracking board LEP icon (PDSA1), standardized documentation using an LEP Form linked to the icon (PDSA2), and included color changes to the icon for team situational awareness (PDSA3). RESULTS: The mean of LEP-SS patients with AIUD improved from 35.7% to 64.5% without significant changes in balancing measures. During the postintervention period (6/1/2018-10/31/2020), no special cause variation was noted from the baseline 48-hour emergency department RV rates for LEP patients (3.1%) or English proficient patients (2.6%). CONCLUSIONS: While the RV rate was not affected, this project is part of a multi-faceted approach aiming to positively impact this outcome measure. Significant improvements in AIUD were achieved without affecting balancing measures.

Use of Lean Healthcare to Improve Hospital Throughput and Reduce LOS.

Improving the discharge process is an area of focus throughout healthcare organizations. Capacity constraints, efficiency improvement, patient safety, and quality care are driving forces for many discharge process workgroups. METHODS: Following the Pareto principle, we focused on improving the discharge process on the medical-surgical units that received the most patients admitted from the emergency department. Increased demand for medical-surgical beds, renovations, and diminished bed capacity made it imperative to improve efficiency using quality improvement techniques. A core team of frontline staff decreased the time between computer entry of discharge orders and patient's departure from the unit to less than 60 minutes, with 80% compliance. The team developed a daily dashboard that detailed the process and outcome measures to create situational awareness and daily visual management. Additional observations of staff workflow uncovered excessive walking for printer use. Printers were placed at the point of use to reduce transport times. Next, using survey results provided by patients on discharge quality, a Treasure Map that aided with teach-back and Team Discharge were implemented to level the staff's workload. Finally, physicians discharged patients earlier in the day. They standardized their discharge criteria to remove subjectivity from the discharge process and enable better team involvement. RESULTS: After implementing 4 interventions, the average time between computer entry of discharge orders and patient's departure from the unit decreased (94.26 versus 65.98 minutes; P < 0.001), simultaneously reducing our average length of stay from 5.62 to 4.81 days (P < 0.001). CONCLUSIONS: In conclusion, hardwiring proven interventions and complementing them with daily visual management led to significant, sustained results.

Use of the Lean Manufacturing Principles to Improve Total Parenteral Nutrition Logistics and Clinical Outcomes in the Neonatal Patient Population.

Total parenteral nutrition (TPN) is one of the most frequently used pharmaceuticals administered to patients in our Neonatal Intensive Care Unit (NICU). Initially, the total interdepartmental processing time (ordering, manufacturing, and delivery between NICU and Pharmacy) averaged 15.2 hours. Inefficiencies in this process only allowed TPN to infuse 8.8 hours on average before labs were collected the next morning. Given the short administration-to-laboratory collection time, we hypothesized that laboratory samples would not adequately reflect the effect of the current TPN infusion. Furthermore, clinicians would be making decisions based on suboptimal data and ultimately nourish this patient population inadequately. METHODS: The project team and the frontline staff created an efficient process for the manufacture and delivery of TPN. They removed waste in the process associated with manufacturing TPN and created capacity for change upstream (ordering process) and downstream (TPN infusion process) of the internal pharmacy process. The use of selection criteria and new standard operating procedures allowed for controlled PDSA testing of changes on a subset of patients. After we attained proven, sustainable results, we scaled the improvement efforts to the entire NICU patient population. RESULTS: After 4 cycles of change, patients now receive TPN on average 14.2 hours before new labs are collected. The interventions over the continuum of this project yielded statistically significant results, increased infusion times to our patients by 61.4% (P < 0.001), improved glucose homeostasis, and decreased average length of stay. CONCLUSIONS: In conclusion, creating process capacity from incremental changes and iterative PDSA cycles has yielded sustained results.

Pediatric Vital Sign Distribution Derived From a Multi-Centered Emergency Department Database.

BACKGROUND: We hypothesized that current vital sign thresholds used in pediatric emergency department (ED) screening tools do not reflect observed vital signs in this population. We analyzed a large multi-centered database to develop heart rate (HR) and respiratory rate centile rankings and z-scores that could be incorporated into electronic health record ED screening tools and we compared our derived centiles to previously published centiles and Pediatric Advanced Life Support (PALS) vital sign thresholds. METHODS: Initial HR and respiratory rate data entered into the Cerner™ electronic health record at 169 participating hospitals' ED over 5 years (2009 through 2013) as part of routine care were analyzed. Analysis was restricted to non-admitted children (0 to <18 years). Centile curves and z-scores were developed using generalized additive models for location, scale, and shape. A split-sample validation using two-thirds of the sample was compared with the remaining one-third. Centile values were compared with results from previous studies and guidelines. RESULTS: HR and RR centiles and z-scores were determined from ~1.2 million records. Empirical 95th centiles for HR and respiratory rate were higher than previously published results and both deviated from PALS guideline recommendations. CONCLUSION: Heart and respiratory rate centiles derived from a large real-world non-hospitalized ED pediatric population can inform the modification of electronic and paper-based screening tools to stratify children by the degree of deviation from normal for age rather than dichotomizing children into groups having "normal" versus "abnormal" vital signs. Furthermore, these centiles also may be useful in paper-based screening tools and bedside alarm limits for children in areas other than the ED and may establish improved alarm limits for bedside monitors.

The use of a pediatric emergency medicine-staffed sedation service during imaging: a retrospective analysis.

HYPOTHESIS: A sedation service staffed by pediatric emergency medicine (PEM) physicians can sedate children during imaging, with a low adverse event risk and minimal sedation failures. DESIGN/METHODS: We reviewed 1042 PEM-administered sedations during a 12-month period, collecting data regarding demographics, presedation evaluation, medications used, sedation length, adverse events, corrective measures, and postsedation disposition. Successful image completion without patient awakening defined effective sedation. Minor adverse events included hypoxia (<93%), malaligned airway, self-resolving transient bradycardia, and atypical reactions to sedation agents. Cardiorespiratory incidents requiring resuscitation were considered major events. RESULTS: Of 923 sedation episodes, 92 (10.0%) experienced adverse events; 7 (0.76%) were major. Sedation failed in 17 (1.8%). No sedation resulted in an increased level of care or permanent injury. CONCLUSIONS: A PEM-staffed sedation service provided sedation to children undergoing imaging with a low adverse event risk, minimal failures, and no residual morbidity. However, all sedating clinicians should possess critical airway skills.

The use of an emergency physician-directed bedside ultrasound examination to clarify a diagnosis in an 8-year-old boy with chronic abdominal pain.

Abdominal pain is a common presenting complaint to the emergency department. Often, patients with chronic, intermittent histories of abdominal pain with multiple visits to medical providers find it difficult to be taken seriously. We describe a patient with a history of episodic abdominal pain who was found to have intermittent ureteropelvic junction obstruction after a timely ultrasound examination by the treating emergency physician.

Effectiveness of oxycodone, ibuprofen, or the combination in the initial management of orthopedic injury-related pain in children.

OBJECTIVE: Orthopedic injuries comprise a majority of the indications for analgesia in the emergency department. Oxycodone and ibuprofen have demonstrated efficacy for this indication, but no studies have compared these drugs in children. Our objective was to investigate the effectiveness of oxycodone, ibuprofen, or their combination for the management of orthopedic injury-related pain in children. METHODS: This prospective, randomized, double-blinded, clinical trial compared the effectiveness of oxycodone, ibuprofen, and the combination in children (age, 6-18 years), with pain from a suspected orthopedic injury. Subjects were block-randomized to receive 1 of the 3 treatment regimens. Pain was assessed with the Faces Pain Scale (FPS) and Visual Analog Scale at baseline, postimmobilization, 30, 60, 90, and 120 minutes postmedication. The change in the FPS score over time was compared between the 3 treatment groups using a generalized estimating equation model. RESULTS: Although all 3 treatment groups demonstrated a decrease in the FPS score over time, there were no significant differences between the groups. Among the 66 total children enrolled in the 3 treatment groups, there were no statistically significant differences in demographics or injury characteristics. There were 28 subjects with fractures. Immobilization of the injury demonstrated a significant reduction in the FPS score. Subjects in the combination treatment group reported more adverse effects. CONCLUSIONS: Oxycodone, ibuprofen, and the combination all provide effective analgesia for mild-to-moderate orthopedic injuries in children. Oxycodone or ibuprofen, alone, can be given, thereby avoiding the increase in adverse effects when given together.

Iatrogenic pleuropulmonary charcoal instillation in a teenager.

Activated charcoal given through a nasogastric tube is a standard intervention for many types of toxic ingestions in the emergency department. This case study describes a teenage girl whose multidrug overdose was complicated by accidental charcoal instillation into her left lung and pleural space through a misplaced nasogastric tube. The ensuing empyema did not respond to antibiotic therapy alone, probably due to the inherent properties of charcoal, and required a chest tube placement with continuous irrigation. Unlike previously reported cases, this patient did well clinically, without long-term morbidity.

Molecular Dissection of the Murine IL-1beta Promoter.

Interleukin-1 (IL-1) is involved in a broad range of biological activities that affect immunological, inflammatory, and nonimmunological responses. Although the role of the IL-1 proteins in normal physiological responses in vivo remains incompletely defined, there is substantial evidence that excessive production of IL-1 contributes to the pathogenesis of many illnesses with autoimmune or inflammatory components, including rheumatoid and osteoarthritis, type I diabetes mellitus and atherosclerosis. Despite numerous reports on IL-1 regulation, very little is known regarding the molecular details of IL-1 production, particularly at the transcription level. This review will focus on our studies of transcriptional regulation of the murine IL-1beta gene and, where appropriate, comparison to similar studies of the human IL-1beta gene. A basic understanding at this level should lead to effective pharmacological intervention and, ultimately, to control of inflammatory disease.

Propofol for procedural sedation in the pediatric emergency department.

This retrospective case series reports our experience using propofol for procedural sedation in the Emergency Department over an 18-month period with 52 pediatric patients. Propofol sedation was performed successfully in all children (mean age, 10.2 years; range 0.7-17.4 years). Indications for sedation included orthopedic manipulation, incision and drainage of abscess, sexual assault examination, laceration repair, and non-invasive imaging studies. The mean dose administered with the intermittent bolus and continuous infusion methods of delivery was 4.25 mg/kg (+/- 1.86) and 8.3 mg/kg/h, respectively. The mean recovery time was 27.1 min (+/- 15.84). No patient required assisted ventilation or developed clinically significant hypotension. Respiratory depression requiring airway repositioning or supplemental oxygen was noted in 5.8% (3/52) patients. Propofol is a reasonable alternative to facilitate sedation for a range of procedures performed in a busy Pediatric Emergency Department.

Designing a pediatric severe sepsis screening tool.

We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). "Gold standard" SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The tool's identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool's predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3 years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an "early" or "late" indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool's positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower.

Use of bedside ultrasonography for endotracheal tube placement in pediatric patients: a feasibility study.

OBJECTIVE: The purpose of our study was to evaluate the usefulness of bedside ultrasonography in verifying endotracheal tube placement in the pediatric population. METHODS: This study consisted of 2 phases. In phase I, subjects were examined while intubated and after extubation to determine the presence of the endotracheal tube by applying each of 2 ultrasound transducers to the cricothyroid membrane. In phase II, pediatric patients were examined in the emergency department during intubation or immediately after intubation to ascertain proper endotracheal tube placement by using bedside ultrasonography. These results were compared with the results obtained with a colorimetric end-tidal carbon dioxide detector and chest radiographs. RESULTS: Forty-nine and 50 patients (age: 1 day to 17 years) were recruited in the first and second phases of the study, respectively. The endotracheal tube was detected in all 99 patients by using bedside ultrasonography. Two views were required to show accurately the presence of the endotracheal tube in the trachea. Visualization was obtained in all cases, although short necks and cervical collars made the procedure more challenging. The sniffing position allowed for the best acquisition of high-quality images. Our linear transducer provided the best images but, because of its size, it was not ideal when space was limited. Therefore, the curvilinear transducer was used exclusively for phase II. During phase II, the mean times to acquire bedside ultrasonographic images of the endotracheal tube through the cricothyroid membrane and to obtain a chest radiograph were 17.1 seconds and 14.0 minutes, respectively. In 3 cases, bedside ultrasonographic images proved to be invaluable when the colorimetric end-tidal carbon dioxide detector yielded false-negative or equivocal readings. CONCLUSIONS: Bedside ultrasonography can be used to accurately and rapidly determine the presence of the endotracheal tube within the trachea in pediatric patients.

Comparison of propofol/fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department.

PURPOSE: To compare the effectiveness of 2 medication regimens, propofol/fentanyl (P/F) and ketamine/midazolam (K/M), for brief orthopedic emergency department procedural sedation. This study was powered to compare recovery times (RT) and procedural distress as measured by the Observational Score of Behavioral Distress-revised (OSBD-r; range: 0-23.5 with 23.5 representing maximal distress). METHODS: We conducted a prospective, partially-blinded controlled comparative trial comparing intravenous P/F with K/M in a convenience sample of 113 patients aged 3 to 18 years old undergoing orthopedic procedural sedation. All medications were administered by the intermittent intravenous bolus method. An independent sedation nurse recorded total sedation time and RT. Effectiveness was measured using 6 parameters: 1) patient distress as assessed by independent blinded observers after videotape review using the OSBD-r; 2) orthopedic satisfaction score (Likert scale 1-5); 3) sedation nurse satisfaction score (Likert 1-5); 4) parental perception of procedural pain using a 0 to 100 mm Visual Analog Scale with the upper limit being "most pain"; 5) patient recall of the procedure; and 6) 1 to 3 week follow-up. RESULTS: RT and total sedation time were significantly less in the P/F group than in the K/M group (33.4 minutes vs 23.2 minutes). The mean OSBD-r scores during manipulation were 0.084 and 0.278 for the K/M and P/F groups, respectively. Although this difference was statistically significant (95% confidence interval for the mean difference -0.34 to -0.048), both regimens were successful in keeping the scores low. There was no statistical difference between the groups in the other measures of effectiveness. There was a statistically significant difference between the groups in the occurrence of desaturation and late side effects. CONCLUSIONS: RT with P/F is shorter than with K/M. P/F is comparable to K/M in reducing procedural distress associated with painful orthopedic procedures in the pediatric emergency department. Although propofol has a greater potential of respiratory depression and airway obstruction as compared with ketamine, it offers some unique advantages including a quicker offset and smoother recovery profile.

Role of vav1 in the lipopolysaccharide-mediated upregulation of inducible nitric oxide synthase production and nuclear factor for interleukin-6 expression activity in murine macrophages.

vav1 has been shown to play a key role in lymphocyte development and activation, but its potential importance in macrophage activation has received little attention. We have previously reported that exposure of macrophages to bacterial lipopolysaccharide (LPS) leads to increased activity of hck and other src-related tyrosine kinases and to the prompt phosphorylation of vav1 on tyrosine. In this study, we tested the role of vav1 in macrophage responses to LPS, focusing on the upregulation of nuclear factor for interleukin-6 expression (NF-IL-6) activity and inducible nitric oxide synthase (iNOS) protein accumulation in RAW-TT10 murine macrophages. We established a series of stable cell lines expressing three mutant forms of vav1 in a tetracycline-regulatable fashion: (i) a form producing a truncated protein, vavC; (ii) a form containing a point mutation in the regulatory tyrosine residue, vavYF174; and (iii) a form with an in-frame deletion of 6 amino acids required for the guanidine nucleotide exchange factor (GEF) activity of vav1 for rac family GTPases, vavGEFmt. Expression of the truncated mutant (but not the other two mutants) has been reported to interfere with T-cell activation. In contrast, we now demonstrate that expression of any of the three mutant forms of vav1 in RAW-TT10 cells consistently inhibited LPS-mediated increases in iNOS protein accumulation and NF-IL-6 activity. These data provide direct evidence for a role for vav1 in LPS-mediated macrophage activation and iNOS production and suggest that vav1 functions in part via activation of NF-IL-6. Furthermore, these findings indicate that the GEF activity of vav1 is required for its ability to mediate macrophage activation by LPS.