A protocol for non-operative management of uncomplicated appendicitis.

BACKGROUND: We developed a protocol to identify candidates for non-operative management (NOM) of uncomplicated appendicitis. Our objective was to evaluate protocol efficacy with the null hypothesis that clinical outcomes, hospital readmission rates, and hospital charges would be unchanged after protocol implementation. METHODS: We performed a single-center 4-year propensity score matched retrospective cohort analysis of 406 patients with acute uncomplicated appendicitis. The protocol recommended NOM for patients with modified Alvarado score ≤6 and no appendicolith. Patients admitted before (n = 203) and after (n = 203) protocol implementation were matched by Charlson comorbidity index, duration of symptoms, and modified Alvarado score. Outcomes included operative management, days on antibiotic therapy, length of stay, and hospital charges, as well as readmissions, complications, and mortality within 180 days. RESULTS: Baseline characteristics were similar between groups (age 31 years, ASA class 2.0, Charlson comorbidity index 0.0). Protocol compliance was higher when the protocol recommended appendectomy (97%) rather than NOM (73%, p < 0.001). The incidence of operative management decreased from 99% to 82% after protocol implementation (p < 0.001). In the protocol group, there was a lower incidence of open surgery (4% vs. 10%, p = 0.044) despite a longer interval between admission and surgery (8.6 vs. 7.1 hours, p < 0.001). After protocol implementation, 51 patients had NOM: 18 failed NOM during admission and 6 failed NOM after discharge. Compared to the pre-protocol group, the protocol group had similar length of stay, antibiotic days, and overall complication rates, but more readmissions (6% vs. 1%, p = 0.019) and lower hospital charges for the index admission ($5,630 vs. $6,878, p < 0.001). CONCLUSIONS: Implementation of a protocol to identify candidates for NOM of acute uncomplicated appendicitis was associated with lower rates of open surgery, fewer appendectomies, decreased hospital charges, and no difference in overall complications despite high rates of readmission and failure of NOM. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Successful nonoperative management of uncomplicated appendicitis: predictors and outcomes.

BACKGROUND: Our objective was to identify predictors of successful nonoperative management (NOM) of uncomplicated appendicitis. We hypothesized that the absence of diabetes, absence of an appendicolith, short duration of symptoms, absence of systemic inflammation, and low modified Alvarado score would predict successful NOM. METHODS: We performed a retrospective cohort analysis of 81 consecutive patients who underwent NOM of uncomplicated appendicitis. Successful NOM was defined as resolution of appendicitis with antibiotics alone and no recurrent appendicitis within 180 days. Patients with successful NOM (n = 36) were compared with patients who failed NOM (n = 45). Multivariable logistic regression was used to identify predictors of successful NOM, expressed as odds ratios (ORs) with 95% confidence intervals. Model strength was assessed by calculating area under the receiver operating characteristic curve (AUC). RESULTS: Patient age (35 years), the American Society of Anesthesiologists class (2.0), and Charlson comorbidity index (0.0) were similar between groups. Independent predictors of successful NOM were duration of symptoms prior to admission >25 hours: OR 4.17 (1.42-12.24), maximum temperature within 6 hours of admission <37.3°C: OR 8.07 (1.79-36.38), modified Alvarado score <4: OR 9.06 (1.26-64.93), and appendiceal diameter <13 mm: OR 17.55 (1.30-237.28); model AUC: 0.81 (0.72-0.90). CONCLUSIONS: Patients with a longer duration of symptoms prior to admission were more likely to have successful NOM. Other independent predictors of successful NOM included lower temperature, lower modified Alvarado score, and smaller appendiceal diameter. These findings provide a framework for clinical decision-making and large-scale derivation and validation of a model to predict successful NOM of uncomplicated appendicitis.

Characterization of hypoalbuminemia following temporary abdominal closure.

BACKGROUND: The purpose of this study was to characterize associations among serum proteins, negative-pressure wound therapy (NPWT) fluid loss, and primary fascial closure (PFC) following emergent laparotomy and temporary abdominal closure (TAC). We hypothesized that high levels of C-reactive protein (CRP) and NPWT output would be associated with hypoalbuminemia and failure to achieve PFC. METHODS: We performed a retrospective analysis of 233 patients managed with NPWT TAC. Serum proteins and resuscitation indices were assessed on admission, initial laparotomy, and then at 48 hours, 96 hours, 7 days, and discharge. Correlations were assessed by Pearson coefficient. Multivariable regression was performed to identify predictors of PFC with cutoff values for continuous variables determined by Youden index. RESULTS: Patients who failed to achieve PFC (n = 55) had significantly higher CRP at admission (249 vs. 148 mg/L, p = 0.003), initial laparotomy (237 vs. 154, p = 0.002), and discharge (124 vs. 72, p = 0.003), as well as significantly lower serum albumin at 7 days (2.3 vs. 2.5 g/dL, p = 0.028) and discharge (2.5 vs. 2.8, p = 0.004). Prealbumin (in milligrams per deciliter) was similar between groups at each time point. There was an inverse correlation between nadir serum albumin and total milliliters of NPWT output (r = -0.33, p < 0.001). Exogenous albumin administration (in grams per day) correlated with higher serum albumin levels at each time point: 48 hours: r = 0.26 (p = 0.002), 96 hours: r = 0.29 (p = 0.002), 7 days: r = 0.40 (p < 0.001). Albumin of less than 2.6 g/dL was an independent predictor of failure to achieve PFC (odds ratio, 2.59; 95% confidence interval, 1.02-6.61) in a multivariate model including abdominal sepsis, body mass index of greater than 40 kg/m, and CRP of greater than 250 mg/L. CONCLUSIONS: Early and persistent systemic inflammation and high NPWT output were associated with hypoalbuminemia, which was an independent predictor of failure to achieve PFC. The utility of exogenous albumin following TAC requires further study. LEVEL OF EVIDENCE: Prognostic study, level III; Therapeutic study, level IV.

Emergent laparotomy and temporary abdominal closure for the cirrhotic patient.

BACKGROUND: Temporary abdominal closure (TAC) may be performed for cirrhotic patients undergoing emergent laparotomy. The effects of cirrhosis on physiologic parameters, resuscitation requirements, and outcomes following TAC are unknown. We hypothesized that cirrhotic TAC patients would have different resuscitation requirements and worse outcomes than noncirrhotic patients. METHODS: We performed a 3-year retrospective cohort analysis of 231 patients managed with TAC following emergent laparotomy for sepsis, trauma, or abdominal compartment syndrome. All patients were initially managed with negative pressure wound therapy (NPWT) TAC with intention for planned relaparotomy and sequential abdominal closure attempts at 24- to 48-h intervals. RESULTS: At presentation, cirrhotic patients had higher incidence of acidosis (33% versus 17%) and coagulopathy (87% versus 54%) than noncirrhotic patients. Forty-eight hours after presentation, cirrhotic patients had a persistently higher incidence of coagulopathy (77% versus 44%) despite receiving more fresh frozen plasma (10.8 units versus 4.4 units). Cirrhotic patients had higher NPWT output (4427 mL versus 2375 mL) and developed higher vasopressor infusion rates (57% versus 29%). Cirrhotic patients had fewer intensive care unit-free days (2.3 versus 7.6 days) and higher rates of multiple organ failure (64% versus 34%), in-hospital mortality (67% versus 21%), and long-term mortality (80% versus 34%) than noncirrhotic patients. CONCLUSIONS: Cirrhotic patients managed with TAC are susceptible to early acidosis, persistent coagulopathy, large NPWT fluid losses, prolonged vasopressor requirements, multiple organ failure, and early mortality. Future research should seek to determine whether TAC provides an advantage over primary fascial closure for cirrhotic patients undergoing emergency laparotomy.

Neural network prediction of severe lower intestinal bleeding and the need for surgical intervention.

BACKGROUND: The prognosis for patients with severe acute lower intestinal bleeding (ALIB) may be assessed by complex artificial neural networks (ANNs) or user-friendly regression-based models. Comparisons between these modalities are limited, and predicting the need for surgical intervention remains elusive. We hypothesized that ANNs would outperform the Strate rule to predict severe bleeding and would also predict the need for surgical intervention. METHODS: We performed a 4-y retrospective analysis of 147 adult patients who underwent endoscopy, angiography, or surgery for ALIB. Baseline characteristics, Strate risk factors, management parameters, and outcomes were analyzed. The primary outcomes were severe bleeding and surgical intervention. ANNs were created in SPSS. Models were compared by area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals. RESULTS: The number of Strate risk factors for each patient correlated significantly with the outcome of severe bleeding (r = 0.29, P < 0.001). However, the Strate model was less accurate than an ANN (AUROC 0.66 [0.57-0.75] versus 0.98 [0.95-1.00], respectively) which incorporated six variables present on admission: hemoglobin, systolic blood pressure, outpatient prescription for Aspirin 325 mg daily, Charlson comorbidity index, base deficit ≥5 mEq/L, and international normalized ratio ≥1.5. A similar ANN including hemoglobin nadir and the occurrence of a 20% decrease in hematocrit was effective in predicting the need for surgery (AUROC 0.95 [0.90-1.00]). CONCLUSIONS: The Strate prediction rule effectively stratified risk for severe ALIB, but was less accurate than an ANN. A separate ANN accurately predicted the need for surgery by combining risk factors for severe bleeding with parameters quantifying blood loss. Optimal prognostication may be achieved by integrating pragmatic regression-based calculators for quick decisions at the bedside and highly accurate ANNs when time and resources permit.

Computed tomography evidence of fluid in the hernia sac predicts surgical site infection following mesh repair of acutely incarcerated ventral and groin hernias.

BACKGROUND: Mesh placement during repair of acutely incarcerated ventral and groin hernias is associated with high rates of surgical site infection (SSI). The utility of preoperative computed tomography (CT) in this setting is unclear. We hypothesized that CT evidence of bowel wall compromise would predict SSI while accounting for physiologic parameters. METHODS: We performed a 4-year retrospective cohort analysis of 50 consecutive patients who underwent mesh repair of acutely incarcerated ventral or groin hernias. We analyzed chronic disease burden, acute illness severity, CT findings, operative management, and herniorrhaphy-specific outcomes within 180 days. The primary outcome was SSI by the Centers for Disease Control and Prevention criteria. Multiple logistic regression was performed to identify independent predictors of SSI. RESULTS: Eighty-four percent of all patients were American Society of Anesthesiologists class III or IV, 28% were active smokers, and mean body mass index (BMI) was 35 kg/m. Fifty-four percent had ventral hernias, 40% had inguinal hernias, and 6% had femoral or combined inguinal/ femoral hernias. Seventy percent of preoperative CT scans had features suggesting bowel compromise, abdominal free fluid, or fluid in the hernia sac. Surgical site infection occurred in 32% of all patients (8% superficial, 24% deep or organ/space). The strongest predictors of SSI were CT evidence of fluid in the hernia sac (odds ratio [OR], 8.3; 95% confidence interval [CI], 1.7-41), initial heart rate 90 beats/min or greater (OR, 6.3; 95% CI, 1.1-34), and BMI 35 kg/m or greater (OR, 5.8; 95% CI, 1.2-28). Surgical site infection rates were significantly higher among patients who had CT evidence of fluid in the hernia sac (56% vs. 19%, p = 0.012). CONCLUSIONS: More than half of all patients with CT scan evidence of fluid in the hernia sac developed an SSI. Computed tomography evidence of fluid in the hernia sac was the strongest predictor of SSI, followed by heart rate and BMI. Together, these parameters identify high-risk patients for whom better strategies are needed to avoid SSI without sacrificing durability. LEVEL OF EVIDENCE: Prognostic study, level III; Therapeutic, level IV.

Early bronchoalveolar lavage for intubated trauma patients with TBI or chest trauma.

PURPOSE: To evaluate the efficacy of an early bronchoalveolar lavage (E-BAL) protocol. BAL was performed within 48 h for intubated patients with traumatic brain injury or chest trauma. We hypothesized that E-BAL would decrease antibiotic use and improve outcomes compared to late BAL (L-BAL) triggered by clinical signs of pneumonia. METHODS: Retrospective cohort analysis of 132 patients with quantitative BAL and ≥1 risk factor: head Abbreviated Injury Score ≥2, ≥3 rib fractures, or radiographic signs of aspiration or pulmonary contusion. E-BAL (n=71) was compared to L-BAL (n=61). Pneumonia was defined as ≥104 organisms on BAL or Clinical Pulmonary Infection Score >6. RESULTS: There were no significant differences in age, injury severity, initial Pao2:Fio2, or smoking status between E-BAL and L-BAL groups. 52% and 61% of the E-BAL and L-BAL cultures were positive, respectively. E-BAL patients had fewer antibiotic days (7.3 vs 9.2, P=.034), ventilator days (11 vs 15, P=.002), tracheostomies (49% vs 75%, P=.002), and shorter intensive care unit and hospital length of stay (13 vs 17 days (P=.007), 18 vs 22 days (P=.041)). CONCLUSIONS: More than half of all E-BAL patients had pneumonia present early after admission. E-BAL was associated with fewer days on antibiotics and better outcomes than L-BAL.

Predicting appendiceal tumors among patients with appendicitis.

BACKGROUND: As nonoperative management of appendicitis gains popularity, vigilance for appendiceal tumors becomes increasingly important. We hypothesized that, among patients presenting with acute appendicitis, those with advanced age, multiple comorbidities, atypical presentation, and complicated appendicitis would be more likely to have underlying appendiceal tumors. METHODS: We performed a 4-year retrospective cohort analysis of 677 consecutive adult patients who underwent appendectomy for appendicitis at our tertiary care center. Patients with an appendiceal tumor on their final pathology report were compared to patients with no tumor. Conditions present on admission were used to create a multivariate logistic regression model to predict appendiceal tumor. Risk factors were reported as odds ratio (OR) [95% CI]. Model strength was assessed by area under the receiver operating characteristic curve. RESULTS: Seventeen patients (2.5%) had an appendiceal tumor. Within this group. 14 underwent immediate appendectomy, two initially had nonoperative management but failed to improve on antibiotics and underwent appendectomy during the initial admission, and one had successful nonoperative management and elective appendectomy 19 days after discharge. Four variables contributed to the multivariate model to predict the presence appendiceal tumor: age ≥ 50 (OR 3.6 [1.1-11.4]), outpatient steroid/immunosuppressant use (OR 12.1 [2.0-72.5]), the absence of migratory right lower quadrant pain (OR 4.7 [1.2-18.1]), and the appearance of a phlegmon on CT scan (OR 7.0 [1.6-30.2]); model area under the receiver operating characteristic curve: 0.860 [0.705-0.969]. CONCLUSION: For patients presenting with acute appendicitis, conditions present on admission may predict underlying appendiceal tumor. Patients with advanced age, multiple comorbidities, atypical presentation, and complicated appendicitis should be considered for appendectomy during the index admission or at earliest convenience if nonoperative management is necessary. LEVEL OF EVIDENCE: Prognostic study, level III.

Antibiotics May be Safely Discontinued Within One Week of Percutaneous Cholecystostomy.

BACKGROUND: For patients with acute cholecystitis managed with percutaneous cholecystostomy (PC), the optimal duration of post-procedural antibiotic therapy is unknown. Our objective was to compare short versus long courses of antibiotics with the hypothesis that patients with persistent signs of systemic inflammation 72 h following PC would receive prolonged antibiotic therapy and that antibiotic duration would not affect outcomes. METHODS: We performed a retrospective cohort analysis of 81 patients who underwent PC for acute cholecystitis at two hospitals during a 41-month period ending November 2014. Patients who received short (≤7 day) courses of post-procedural antibiotics were compared to patients who received long (>7 day) courses. Treatment response to PC was evaluated by systemic inflammatory response syndrome (SIRS) criteria. Logistic and linear regressions were used to evaluate associations between antibiotic duration and outcomes. RESULTS: Patients who received short (n = 30) and long courses (n = 51) of antibiotics had similar age, comorbidities, severity of cholecystitis, pre-procedural vital signs, treatment response, and culture results. There were no differences in recurrent cholecystitis (13 vs. 12%), requirement for open/converted to open cholecystectomy (23 vs. 22%), or 1-year mortality (20 vs. 18%). On logistic and linear regressions, antibiotic duration as a continuous variable was not predictive of any salient outcomes. CONCLUSIONS: Patients who received short and long courses of post-PC antibiotics had similar baseline characteristics and outcomes. Antibiotic duration did not predict recurrent cholecystitis, interval open cholecystectomy, or mortality. These findings suggest that antibiotics may be safely discontinued within one week of uncomplicated PC.

Acute Kidney Injury Following Exploratory Laparotomy and Temporary Abdominal Closure.

BACKGROUND: Acute kidney injury (AKI) following exploratory laparotomy and temporary abdominal closure (TAC) is poorly understood but clinically significant. We hypothesized that the prevalence of AKI would be highest 96 h following TAC, early hypoxemia would predict AKI, and that AKI would be an independent predictor of mortality. METHODS: We performed a retrospective analysis of 251 acute care surgery patients managed with TAC by negative pressure wound therapy (NPWT). Kidney Disease: Improving Global Outcomes AKI stages were assessed on admission, initial TAC, and following TAC at 48 h, 96 h, and 7 d. Multivariate regression was performed to identify risk factors for AKI and inpatient mortality. RESULTS: Fifty-seven percent of all patients developed AKI within 7 days of laparotomy (stage 1: 14%, 2: 21%, 3: 22%). The prevalence of AKI peaked 48 h following TAC, and stage correlated with inpatient mortality (stage 0: 7%, 1: 13%, 2: 19%, 3: 37%, P < 0.001). Overall mortality was 14%. Factors predictive of stage 2 or 3 AKI at 48 h included age >65 years (OR 2.6 [95% CI 1.4-4.9]), NPWT output >30 mL/h from first TAC to 48 h (2.0 [1.1-3.9]), and three parameters at initial laparotomy: mean arterial pressure <60 mm Hg (2.9 [1.0-8.5]), temperature <36°C (2.1 [1.1-3.8]), and anion gap >21 mEq/L (1.9 [1.0-3.7]). AKI was an independent predictor of inpatient mortality (5.5 [2.5-11.8]). CONCLUSIONS: AKI is common following TAC, reaches greatest prevalence 48 h after initial laparotomy, and is associated with increased mortality. NPWT fluid loss is a risk factor for AKI that is unique to TAC patients.

Improved outcomes following implementation of an acute gastrointestinal bleeding multidisciplinary protocol.

BACKGROUND: Effective multidisciplinary management of gastrointestinal bleeding (GIB) requires effective communication. We instituted a protocol to standardize communication practices with the hypothesis that outcomes would improve following protocol initiation. METHODS: We performed a retrospective cohort analysis of 442 patients who required procedural management of acute GIB at our institution during a 50-month period spanning 25 months before and 25 months after implementation of a multidisciplinary communication protocol. The protocol stipulates that when a patient with severe GIB is identified, a conference call is coordinated among the gastroenterology, interventional radiology, and acute care surgery teams. A consensus plan is generated and then reassessed following procedural interventions and changes in patients' status. Patients' characteristics, management strategies, and outcomes were compared before and after protocol initiation. RESULTS: Patient populations before and after protocol initiation were similar in age, comorbidities, outpatient use of antiplatelet/anticoagulant medications, admission vital signs, and admission laboratory values. The median interval between admission and the first procedure was significantly shorter in the protocol group (40 vs 47 hours, p = 0.046). The proportion of patients who received packed red blood cell transfusions decreased following protocol initiation (41% vs 50%, p = 0.018). Median hospital length of stay was significantly shorter in the protocol group (5.0 vs 6.0 days, p = 0.014). Readmissions with GIB were decreased after protocol implementation (8% vs. 15%, p = 0.023). CONCLUSION: Implementation of a multidisciplinary protocol for management of acute GIB was associated with earlier intervention, fewer packed red blood cell transfusions, shorter hospital length of stay, and fewer readmissions with GIB. Future research should seek to establish causal relationships between communication practices and outcomes. LEVEL OF EVIDENCE: Therapeutic study, level III.

Routine surveillance cholangiography after percutaneous cholecystostomy delays drain removal and cholecystectomy.

INTRODUCTION: Percutaneous cholecystostomy (PC) is often performed for patients with acute cholecystitis who are at high risk for operative morbidity and mortality. However, the necessity for routine cholangiography after PC remains unclear. We hypothesized that routine surveillance cholangiography (RSC) after PC would provide no benefit compared to on-demand cholangiography (ODC) triggered by signs or symptoms of biliary pathology. METHODS: We performed a 3-year retrospective cohort analysis of patients managed with PC for acute cholecystitis at two tertiary care hospitals. Patients who had routine surveillance cholangiography (RSC, n = 43) were compared to patients who had on-demand cholangiography (ODC, n = 41) triggered by recurrent biliary disease. RESULTS: RSC and ODC groups were similar by severity of acute cholecystitis, presence of gallstones, systemic inflammatory response syndrome (SIRS) criteria at the time of PC, SIRS criteria 72 hours after PC, and hospital length of stay. Two patients in the ODC group developed clinical indications for cholangiography. All 44 RSC patients had cholangiography, and 67 total cholangiograms were performed in this group. Surveillance cholangiography identified six patients (14%) with cystic duct filling defect and seven patients (16%) with a common bile duct filling defect, all of whom were asymptomatic. Fifteen patients (35%) in the RSC group had 32 ERCP procedures; five patients (12%) in the ODC group had 7 ERCPs (p = 0.021). The ODC group had fewer days to drain removal (35 vs. 61, p < 0.001) and days to cholecystectomy (39 vs. 81, p = 0.005). Rates of recurrent cholecystitis, cholangitis, gallstone pancreatitis, drain removal, and cholecystectomy were similar between groups. CONCLUSION: RSC after PC for acute cholecystitis identified biliary pathology in asymptomatic patients and propagated further testing, but did not provide clinical benefit. ODC was associated with earlier drain removal, earlier cholecystectomy, and decreased resource utilization. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

Temporary abdominal closure for trauma and intra-abdominal sepsis: Different patients, different outcomes.

BACKGROUND: Temporary abdominal closure (TAC) after damage control surgery (DCS) for injured patients has been generalized to septic patients. However, direct comparisons between these populations are lacking. We hypothesized that patients with intra-abdominal sepsis would have different resuscitation requirements and lower primary fascial closure rates than trauma patients. STUDY DESIGN: We performed a 3-year retrospective cohort analysis of patients managed with TAC for trauma (n = 77) or intra-abdominal sepsis (n = 147). All patients received negative pressure wound therapy (NPWT) TAC with intention for planned relaparotomy and sequential abdominal closure attempts at 24- to 48-hour intervals. RESULTS: At presentation, trauma patients had higher rates of hypothermia (31% vs. 18%), severe acidosis (27% vs. 14%), and coagulopathy (68% vs. 48%), and septic patients had higher vasopressor infusion rates (46% vs. 27%). Forty-eight hours after presentation, septic patients had persistently higher vasopressor infusion rates (37% vs. 17%), and trauma patients had received more red blood cell transfusions (6.0 U vs. 0.0 U), fresh frozen plasma (5.0 U vs. 0.0 U), and crystalloid (8,290 vs. 7,159 ml). Among patients surviving to discharge, trauma patients had higher primary fascial closure (PFC) rates (90% vs. 76%). For trauma patients, independent predictors of failure to achieve PCF were ≥2.5 L NPWT output at 48 hours, ≥10 L crystalloid administration at 48 hours, and ≥10 U PRBC + FFP at 48 hours. For septic patients, relaparotomy within 48 hours predicted successful PFC; requirement for ≥3 diagnostic/therapeutic laparotomies predicted failure to achieve PFC. CONCLUSIONS: Traumatic injury and intra-abdominal sepsis are associated with distinct pathophysiologic insults, resuscitation requirements, and outcomes. Failure to achieve primary fascial closure in trauma patients was attributable to the triad of hypothermia, acidosis, and coagulopathy; failure to achieve fascial closure in septic patients was dependent upon operative course. Indications and optimal techniques for TAC may differ between these populations. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

Intubated Trauma Patients Receiving Prolonged Antibiotics for Pneumonia despite Negative Cultures: Predictors and Outcomes.

BACKGROUND: Despite the excellent negative predictive value of sterile respiratory cultures, antibiotics often are continued after negative endotracheal aspirate (ETA) or bronchoalveolar lavage (BAL) for critically ill trauma patients. We hypothesized that persistent elevation of the Clinical Pulmonary Infection Score (CPIS) would predict continued antibiotic therapy after a negative respiratory culture for intubated trauma patients, and that prolonged antibiotics would provide no benefit. METHODS: We performed a four-year retrospective cohort analysis (May 1, 2011-September 30, 2015), including patients from our trauma database with ETA or BAL, excluding patients with any infection other than pneumonia or bacteremia. Cultures with <2+ organisms on gram stain and <2+ or 104 organisms on culture were considered negative. The CPIS was assessed at the time of culture and five days later, when all cultures were final. Multiple logistic regression was used to identify predictors of long-term antibiotic therapy. RESULTS: A series of 106 patients with negative cultures were included, of whom 61 had ≤5 d of antibiotics and 45 had >5 d of antibiotics. There were no differences in injury severity, head or chest trauma, initial CPIS, or subsequent culture results between the groups. Long-term antibiotic therapy did not affect intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, or death. Factors predicting long-term antibiotic therapy included development of a localized chest radiograph infiltrate (odds ratio [OR] 6.8; 95% confidence interval [CI] 1.7-28), CPIS >5 five days after culture (OR 6.1; 95% CI 1.2-32), and a colonized culture (OR 3.3; 95% CI 1.3-8.3). CONCLUSIONS: Long-term antibiotic therapy for intubated trauma patients with negative respiratory cultures provided no benefit and was predicted by development of a localized chest radiograph infiltrate, persistently elevated CPIS, and a contaminated/colonized culture. Although long-term antibiotic use did not worsen outcomes, better strategies are needed to diagnose pneumonia accurately and ensure timely discontinuation of antibiotics when appropriate.

Dynamic changes in rat mesenteric lymph proteins following trauma using label-free mass spectrometry.

Early events triggered by posttrauma/hemorrhagic shock currently represent a leading cause of morbidity and mortality in these patients. The causative agents of these events have been associated with increased neutrophil priming secondary to shock-dependent alterations of mesenteric lymph. Previous studies have suggested that unknown soluble components of the postshock mesenteric lymph are main drivers of these events. In the present study, we applied a label-free proteomics approach to further delve into the early proteome changes of the mesenteric lymph in response to hemorrhagic shock. Time-course analyses were performed by sampling the lymph every 30 min after shock up until 3 h (the time window within which a climax in neutrophil priming was observed). There are novel, transient early post-hemorrhagic shock alterations to the proteome and previously undocumented postshock protein alterations. These results underlie the triggering of coagulation and proinflammatory responses secondary to trauma/hemorrhagic shock, metabolic deregulation and apoptosis, and alterations to proteases/antiproteases homeostasis, which are suggestive of the potential implication of extracellular matrix proteases in priming neutrophil activation. Finally, there is a likely correlation between early postshock mesenteric lymph-mediated neutrophil priming and proteomics changes, above all protease/antiproteases impaired homeostasis (especially of serine proteases and metalloproteases).

Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential gel electrophoresis and mass spectrometry analysis.

Experiments show that upon traumatic injury the composition of mesenteric lymph changes such that it initiates an immune response that can ultimately result in multiple organ dysfunction syndrome (MODS). To identify candidate protein mediators of this process we carried out a quantitative proteomic study on mesenteric lymph from a well characterized rat shock model. We analyzed three animals using analytical 2D differential gel electrophoresis. Intra-animal variation for the majority of protein spots was minor. Functional clustering of proteins revealed changes arising from several global classes that give novel insight into fundamental mechanisms of MODS. Mass spectrometry based proteomic analysis of proteins in mesenteric lymph can effectively be used to identify candidate mediators and loss of protective agents in shock models.

Proteome and system ontology of hemorrhagic shock: exploring early constitutive changes in postshock mesenteric lymph.

BACKGROUND: Postshock mesenteric lymph (PSML) is the mechanistic link between splanchnic ischemia reperfusion (IR) and remote organ injury. We hypothesize that an unbiased inspection of the proteome of PSML will reveal previously unrecognized aberrations in systems biology provoked by hemorrhage-induced mesenteric IR injury in vivo. METHODS: Shock was induced in male Sprague-Dawley rats by controlled hemorrhage, and the mesenteric duct was cannulated for lymph collection. Preshock and postshock lymph were collected for differential in-gel electrophoresis (DIGE)-based proteomics. Proteins that increased or decreased in relative concentration > or =1.5-fold were selected for trypsin digestion and analysis by mass spectrometry (MS). RESULTS: Evidence of tissue injury was detected by an increase in cell/tissue proteins in PSML. Components of coagulation were depleted, whereas products of hemolysis were increased. Haptoglobin was decreased, which supports an early postshock hemolytic process. Interestingly, several protective protease inhibitors were decreased in PSML. The unexpected findings were an increase in alpha-enolase (a key glycolitic enzyme and cell-surface plasminogen binding receptor, +2.4-fold change) and increased major urinary protein (MUP, a sex-specific lipid-binding protein, +17.1-fold change) in PSML. CONCLUSION: A proteomic evaluation of PSML revealed evidence of several shock-associated processes: protein release from tissue injury, depletion of coagulation factors and evidence of hemolysis, depletion of protective protease inhibitors, and an increase in abundance of lipid carriers. These results suggest that constitutive changes in the proteome of PSML may provide novel insights into the complex pathophysiology of postshock systems biology.