Saman Arbabi

Extracorporeal Life Support for Severe Acute Respiratory Distress Syndrome in Adults

Objective:Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. Methods:We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio ≤100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung “rest” at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. Results:During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH ≤7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. Conclusion:Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.

Long-term survival of adult trauma patients

CONTEXT Inpatient trauma case fatality rates may provide an incomplete assessment for overall trauma care effectiveness. To date, there have been few large studies evaluating long-term mortality in trauma patients and identifying predictors that increase risk for death following hospital discharge. OBJECTIVES To determine the long-term mortality of patients following trauma admission and to evaluate survivorship in relationship with discharge disposition. DESIGN, SETTING, AND PATIENTS Retrospective cohort study of 124,421 injured adult patients during January 1995 to December 2008 using the Washington State Trauma Registry linked to death certificate data. MAIN OUTCOME MEASURES Kaplan-Meier and Cox proportional hazards models were used to evaluate long-term mortality following hospital admission for trauma. RESULTS Of the 124,421 trauma patients, 7243 died before hospital discharge and 21,045 died following hospital discharge. Cumulative mortality at 3 years postinjury was 16% (95% confidence interval [CI], 15.8%-16.2%) compared with the expected population cumulative mortality of 5.9% (95% CI, 5.9%-5.9%). In-hospital mortality improved during the 14-year study period from 8% (n = 362) to 4.9% (n = 600), whereas long-term cumulative mortality increased from 4.7% (95% CI, 4.1%-5.4%) to 7.4% (95% CI, 6.8%-8.1%). After adjustments for confounders, patients who were older and those who were discharged to a skilled nursing facility had the highest risk of death. The adjusted hazard ratios (HRs) for death after discharge to a skilled nursing facility compared with that after discharge home were 1.41 (95% CI, 0.72-2.76) for patients aged 18 to 30 years, 1.92 (95% CI, 1.36-2.73) for patients aged 31 to 45 years, 2.02 (95% CI, 1.39-2.93) for patients aged 46 to 55 years, 1.93 (95% CI, 1.40-2.64) for patients aged 56 to 65 years, 1.49 (95% CI, 1.14-1.94) for patients aged 66 to 75 years, 1.54 (95% CI, 1.27-1.87) for patients aged 76 to 80 years, and 1.38 (95% CI, 1.09-1.74) for patients older than 80 years. Other significant predictors of mortality after discharge included maximum head injury score on Abbreviated Injury Score scale (HR, 1.20; 95% CI, 1.13-1.26), Injury Severity Score (HR, 0.98; 95% CI, 0.97-0.98), Functional Independence Measure (HR, 0.89; 95% CI, 0.88-0.91), mechanism of injury being a fall (HR, 1.43; 95% CI, 1.30-1.58), and having Medicare (HR, 1.28; 95% CI, 1.15-1.43) or other government insurance (HR, 1.65; 95% CI, 1.47-1.85). CONCLUSIONS Among adults admitted for trauma in Washington State, 3-year cumulative mortality was 16% despite a decline in in-hospital deaths. Discharge to a skilled nursing facility at any age following trauma admission was associated with a higher risk of subsequent mortality.

An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction

Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a–C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance.

Introduction to propensity scores: A case study on the comparative effectiveness of laparoscopic vs open appendectomy.

OBJECTIVE To demonstrate the use of propensity scores to evaluate the comparative effectiveness of laparoscopic and open appendectomy. DESIGN Retrospective cohort study. SETTING Academic and private hospitals. PATIENTS All patients undergoing open or laparoscopic appendectomy (n = 21 475) in the Public Use File of the American College of Surgeons National Surgical Quality Improvement Program were included in the study. We first evaluated the surgical approach (laparoscopic vs open) using multivariate logistic regression. We next generated propensity scores and compared outcomes for open and laparoscopic appendectomy in a 1:1 matched cohort. Covariates in the model for propensity scores included comorbidities, age, sex, race, and evidence of perforation. MAIN OUTCOME MEASURES Patient morbidity and mortality, rate of return to operating room, and hospital length of stay. RESULTS Twenty-eight percent of patients underwent open appendectomy, and 72% had a laparoscopic approach; 33% (open) vs 14% (laparoscopic) had evidence of a ruptured appendix. In the propensity-matched cohort, there was no difference in mortality (0.3% vs 0.2%), reoperation (1.8% vs 1.5%), or incidence of major complications (5.9% vs 5.4%) between groups. Patients undergoing laparoscopic appendectomy experienced fewer wound infections (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3-0.5) and fewer episodes of sepsis (0.8; 0.6-1.0) but had a greater risk of intra-abdominal abscess (1.7; 1.3-2.2). An analysis using multivariate adjustment resulted in similar findings. CONCLUSIONS After accounting for patient severity, open and laparoscopic appendectomy had similar clinical outcomes. In this case study, propensity score methods and multivariate adjustment yielded nearly identical results.

Porphyromonas gingivalis Lipopolysaccharide Is Both Agonist and Antagonist for p38 Mitogen-Activated Protein Kinase Activation

ABSTRACT Lipopolysaccharide (LPS) is a key inflammatory mediator. It has been proposed to function as an important molecule that alerts the host of potential bacterial infection. Although highly conserved, LPS contains important structural differences among different bacterial species that can significantly alter host responses. For example, LPS obtained from Porphyromonas gingivalis, an etiologic agent for periodontitis, evokes a highly unusual host cell response. Human monocytes respond to this LPS by the secretion of a variety of different inflammatory mediators, while endothelial cells do not. In addition, P. gingivalis LPS inhibits endothelial cell expression of E-selectin and interleukin 8 (IL-8) induced by other bacteria. In this report the ability of P. gingivalis LPS to activate p38 mitogen-activated protein (MAP) kinase was investigated. It was found that p38 MAP kinase activation occurred in response to P. gingivalis LPS in human monocytes. In contrast, no p38 MAP kinase activation was observed in response to P. gingivalis LPS in human endothelial cells or CHO cells transfected with human Toll-like receptor 4 (TLR-4). In addition, P. gingivalis LPS was an effective inhibitor of Escherichia coli-induced p38 MAP kinase phosphorylation in both endothelial cells and CHO cells transfected with human TLR-4. These data demonstrate that P. gingivalis LPS activates the LPS-associated p38 MAP kinase in monocytes and that it can be an antagonist for E. coli LPS activation of p38 MAP kinase in endothelial and CHO cells. These data also suggest that although LPS is generally considered a bacterial component that alerts the host to infection, LPS from P. gingivalis may selectively modify the host response as a means to facilitate colonization.

Intensive insulin therapy is associated with reduced infectious complications in burn patients

BACKGROUND Intensive insulin therapy to control blood glucose levels has reduced mortality in surgical, but not medical, intensive care unit (ICU) patients. Control of blood glucose levels has also been shown to reduce morbidity in surgical ICU patients. There is very little data for use of intensive insulin therapy in the burn patient population. We sought to evaluate our experience with intensive insulin therapy in burn-injured ICU patients with regard to mortality, morbidity, and use of hospital resources. STUDY DESIGN Burn patients admitted to our American College of Surgeons verified burn center ICU from 7/1/2004 to 6/30/2006 were studied. An intensive insulin therapy protocol was initiated for ICU patients admitted starting 7/1/2005 with a blood glucose target of 100-140 mg/dL. The 2 groups of patients studied were control (7/1/2004 to 6/30/2005) and intensive insulin therapy (7/1/2005 to 6/30/2006). All glucose values for the hospitalization were analyzed. Univariate and multivariate analyses were performed. RESULTS Overall, 152 ICU patients admitted with burn injury were available for study. No difference in mortality was evident between the control and intensive insulin therapy groups. After adjusting for patient risk, the intensive insulin therapy group was found to have a decreased rate of pneumonia, ventilator-associated pneumonia, and urinary tract infection. In patients with a maximum glucose value of greater than 140 mg/dL, the risk for an infection was significantly increased (OR 11.3, 95% CI 4-32, P-value < .001). The presence of a maximum glucose value greater than 140 mg/dL was associated with a sensitivity of 91% and specificity of 62% for an infectious complication. CONCLUSION Intensive insulin therapy for burn-injured patients admitted to the ICU was associated with a reduced incidence of pneumonia, ventilator-associated pneumonia, and urinary tract infection. Intensive insulin therapy did not result in a change in mortality or length of stay when adjusting for confounding variables. Measurement of a blood glucose level greater than 140 mg/dL should heighten the clinical suspicion for the presence of an infection in patients with burn injury.

Angioembolization reduces operative intervention for blunt splenic injury.

BACKGROUND Nonoperative management for blunt splenic injury (BSI) has become gold standard, but the role of angiographic embolization (AE) is still controversial for bleeding. We postulated that splenic AE for BSI would have superior outcomes compared with operation and increase our splenic salvage rate. METHODS This was a retrospective study of all adult trauma patients admitted to our Level I center from 2000 through 2006. Multivariate analysis adjusting for age, Injury Severity Score, and Glasgow Coma Scale score was performed. Only patients who had a computed tomographic (CT) scan before surgery (CT + OR) were compared with those who had CT scans then AE. RESULTS Eighty-seven of 317 patients required initial intervention for their BSI, for a no intervention rate (no OR or AE) of 73% and a nonoperative rate of 89%. The groups had similar Injury Severity Score, mortality, and lengths of stay. The AE group was older (p < 0.01), had higher spleen Abbreviated Injury Score (p = 0.02), and required significantly fewer packed RBC transfusions, p < 0.01. The overall hospitalization costs were not different, but the number of intraabdominal complications was higher for the CT + OR group (36% vs. 6%, p < 0.01). Pneumonia, thromboembolic events, and pleural effusions were equivalent. There were no deaths from splenic hemorrhage. CONCLUSION Despite recent concerns that AE may be overutilized for BSI, this study showed a lower incidence of abdominal complications and blood utilization in the AE group despite an older age and higher splenic Abbreviated Injury Score. Use of AE decreased operative intervention by 16%.

Near-infrared spectroscopy: A potential method for continuous, transcutaneous monitoring for compartmental syndrome in critically injured patients

BACKGROUND Near-infrared spectroscopy (NIRS) noninvasively measures tissue O2 saturation (StO2), and has been proposed as a means of monitoring for compartmental syndrome (CS). However, its specificity in hypoxemic, hypotensive patients with severely reduced systemic oxygen delivery has not been tested. We hypothesized that NIRS can differentiate muscle ischemia caused by shock from ischemia caused by CS. METHODS Nine swine were anesthetized and an NIRS probe placed over the anterolateral compartment of the hind leg. Compartment pressure was also measured. A nerve stimulator was placed over the peroneal nerve, and CS was defined as loss of dorsiflexion twitch. At 30-minute sequential intervals, mean arterial blood pressure was reduced to 60% of baseline (phlebotomy), fraction of inspired oxygen was reduced to 0.15, and compartment pressure was increased in one limb by interstitial albumin infusion until CS occurred. RESULTS Hypotension combined with hypoxemia reduced StO2 from 82+/-4% to 66+/-10%. CS further reduced StO2 to 16+/-12% (p<0.0001). During hypotension + hypoxemia + CS, control limb StO2 was 70+/-15% (p = 0.0002 vs. experimental limb). CONCLUSION NIRS detects muscle ischemia caused by CS despite severe hypotension and hypoxemia, making it potentially useful in critically injured, unstable patients.

Advances in burn critical care

Background:Management of burn patients requires a complex interaction of surgical, medical, critical care, and rehabilitation approaches. Severe burn patients are some of the most challenging critically ill patients who may have multiple-system organ failure with life-threatening complications. Objective:To review and highlight some of the recent advances in burn critical care. We focused on some of the new treatment modalities in the management of respiratory complications, advances in burn resuscitation, management of the metabolic response to burns, and recent ideas in burn immunotherapy. Data Source:A search of the MEDLINE database and manual review of published articles and abstracts from national and international meetings. Data Syntheses and Conclusions:The respiratory management of burn patients includes strategies to minimize iatrogenic injury with low tidal volume ventilation, to improve ventilation/perfusion mismatch, and to diagnosis pneumonia. Many aspects of burn resuscitation remain controversial, and the best form of fluid resuscitation has yet to be identified. Recent research in the metabolic response to thermal injury has identified many potentially beneficial treatments. Although immunomodulation therapy is promising, currently most of these treatments are not clinically viable, and further clinical and translational research is warranted.

Delayed Repair for Blunt Thoracic Aortic Injury: Is it Really Equivalent to Early Repair?

BACKGROUND Blunt thoracic aortic injury (BTAI) is a severe injury that traditionally has mandated immediate surgical repair. Delaying operative intervention for BTAI can allow other life-threatening injuries to be managed first, but potentially increases the risk of aortic rupture and death. The objective of this study was to evaluate the outcome of delayed repair (DR) compared with early repair (ER) for BTAI and to assess the effectiveness of a protocol for medical control of systolic blood pressure and heart rate in those patients whose repairs were delayed. METHODS This study is a retrospective review of University of Michigan Health System (UMHS) data from January 1, 1992, through March 1, 2003. ER was defined as operative repair within 16 hours from the time of injury. A similar analysis was conducted for patients with BTAI selected from the National Trauma Data Bank. RESULTS For the UMHS data, there were 45 patients in the DR group and 33 patients in the ER group. Mortality in the ER group versus the DR group was 9% versus 20%. Multivariate analysis adjusting for age, Injury Severity Score, abdominal Abbreviated Injury Scale score, Glasgow Coma Scale score, and intubation status demonstrated an odds ratio for death from ER compared with DR of 1.72 (p = 0.57). Patients undergoing DR had an absolute increase in hospital length of stay (33.1 vs. 20.9 days) and complication rate (2.1 vs. 1.5 incidents per patient). A similar result was obtained for multivariate analysis of the National Trauma Data Bank data, with an odds ratio of 1.40 (p = 0.51) for death from ER versus DR. UMHS patients whose repairs were delayed achieved target systolic blood pressure and heart rate for 76% and 74% of the hourly measurements recorded, respectively. CONCLUSION Patients with BTAI can safely undergo delayed aortic repair if other injuries warrant a higher treatment priority without increasing their overall risk of mortality. Delayed repair is, however, associated with a higher complication rate.