Florence Riché

Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: A randomized controlled study

BACKGROUND The diagnostic and therapeutic value of EGD in patients with upper GI bleeding is often limited by the presence of residual blood or clots. When infused before EGD, erythromycin, a potent gastrokinetic drug, might improve the quality of EGD in patients with upper GI bleeding. The aim of this study was to assess the effect of erythromycin on the quality of the EGD in patients with acute upper GI bleeding. METHODS Forty-one patients admitted to the intensive care unit because of acute upper GI bleeding were included in a randomized, endoscopist-blinded, controlled trial, comparing erythromycin (3 mg/kg intravenously over 30 minutes) to no treatment (control patients). EGD was performed 30 to 90 minutes after the end of the infusion. The primary study outcome was quality of EGD examination, as evaluated on a scale of 0 to 3, and the need to perform a second diagnostic EGD within the next 8 days. Secondary outcomes were efficiency of the endoscopic hemostatic therapy and intensity of esophagogastroduodenal contractions, as evaluated on a scale of 0-3. RESULTS The characteristics of the patients and lesions found by EGD were similar in both groups. Quality of the EGD examination was significantly better in the erythromycin group (n = 19) compared with the control group (n = 22) (2.5 [0.8] vs. 1.5 [1.3]; p = 0.02). Three patients receiving erythromycin required a second EGD compared with 10 control patients (p = 0.089). Erythromycin did not interfere with the performance of EGD or the efficiency of hemostatic procedures. The intensity of gastroduodenal contractions was similar in both groups. No adverse event was observed. CONCLUSIONS In patients with acute upper GI bleeding, infusion of erythromycin before endoscopy significantly improved the quality of EGD and tended to reduce the need for second-look endoscopy.

Inflammatory cytokine response in patients with septic shock secondary to generalized peritonitis

Objectives: The aims of this study were the following: a) to assess the proinflammatory cytokine (tumor necrosis factor [TNF]‐α, interleukin [IL]‐1, and IL‐6) response in patients with septic shock secondary to generalized peritonitis; and b) to evaluate the influence of bacteremic status, type of peritonitis (acute perforation or postoperative), and peritoneal microbial status (mono‐ or polymicrobial) on cytokine expression and mortality. Design: Prospective study. Setting: Surgical intensive care unit of a university hospital. Patients: Fifty‐two consecutive patients with septic shock caused by generalized peritonitis. Interventions: Routine blood tests, blood cultures, and cytokine assays were performed during the first 3 days after onset of shock. Measurements and Main Results: Serum TNF‐α and IL‐6 concentrations were measured by using a radioimmunoassay, and IL‐1 concentrations were measured by using ELISA. Median serum concentrations on day 1 were: TNF‐α, 90 pg/mL; IL‐1, 7 pg/mL; and IL‐6, 5000 pg/mL. TNF‐α and IL‐6 concentrations decreased significantly between the first and third days of septic shock (p = .0001), whereas IL‐1 concentrations remained low. The decrease in IL‐6 tended to be more pronounced in the survivors group (p = .057). Median TNF‐α serum concentrations were higher in bacteremic compared with nonbacteremic patients (151 vs. 73 pg/mL, p = .003). TNF‐α, IL‐1, and IL‐6 serum concentrations and mortality were not different between acute perforation vs. postoperative peritonitis and mono‐ versus polymicrobial peritonitis. Conclusions: The systemic release of TNF‐α and IL‐6 during septic shock caused by generalized peritonitis was maximal on day 1 and decreased rapidly during the next days. No systemic release of IL‐1 was observed. IL‐6 serum concentrations remained higher in patients who subsequently died. Among the different features of peritonitis studied, only bacteremia influenced the systemic cytokine response (higher TNF‐α).

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

IntroductionThe risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.MethodsThis was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).ResultsFrequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.ConclusionsUnlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: A prospective study in 59 patients

BACKGROUND In several studies including patients with septic shock of various origins, high serum cytokine levels have been reported to correlate with poor outcome. The aim of this prospective study was to assess the prognostic value of cytokine serum levels in a group of patients with perioperative septic shock of digestive origin. METHODS From January 1992 to December 1994, 59 patients were evaluated (mean age, 68 +/- 15 years). From the first day of septic shock to day 7, blood was drawn every day to measure the conventional biologic parameters (white blood cell count, platelet count, hematocrit, blood urea nitrogen level, serum electrolytes level, pH, blood gases, serum lactate level, coagulation parameters, liver function tests) and tumor necrosis factor (TNF), interleukin-1, and interleukin-6. RESULTS No difference was observed between the 26 survivors and the 33 nonsurvivors with regard to age, gender, and cause of sepsis. On admission, mean platelet count was significantly higher in the survivors than in the nonsurvivors (260 +/- 142 versus 177 +/- 122 10(9)/L; p = 0.01). Mean blood urea nitrogen level was significantly lower in the survivors than in the nonsurvivors (9.6 +/- 9 versus 12 +/- 7 mmol/L; p = 0.04). No difference was observed between survivors and nonsurvivors for the other conventional biologic parameters and for serum interleukin-1 and interleukin-6 levels. Mean serum TNF level tended to be higher in survivors than in nonsurvivors (565 +/- 1325 versus 94 +/- 69 pg/ml; not significant). In the group survivor 9 (35%) of 26 patients had a serum TNF level greater than 200 pg/ml versus 2 (6%) of 33 patients in the nonsurvivor group (p < 0.02). Survival was noted in 6 (100%) of 6 patients who had both a serum TNF level greater than 200 pg/ml and a platelet count greater than 100.10(9)/L versus 1 (11%) of 9 in patients with neither of these criteria (p < 0.01). CONCLUSIONS In our patients with abdominal septic shock, high serum TNF levels were associated with increased survival. The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. Although this possibility must be further explored, a score combining the serum TNF level and platelet count could be helpful for the prognostic assessment of patients with abdominal septic shock.

Serial computed tomography is rarely necessary in patients with acute pancreatitis : A prospective study in 102 patients

BACKGROUND CT has proved to be helpful in patients with acute pancreatitis for differentiating between mild and severe forms. Followup of acute pancreatitis with CT has been advocated but rarely studied. The aim of this study was to determine if late CT performed at day 7 might be helpful in establishing the prognosis or the type of complications, and to select a subgroup of patients in whom CT could be beneficial. STUDY DESIGN Contrast-enhanced CT was performed at the admission day and 7 days after admission in 102 patients admitted for acute pancreatitis. The extent of pancreatic inflammation was classified according to Balthazar grade, and intrapancreatic necrosis on these examinations was prospectively assessed and compared with clinical and biologic data and with patient outcomes. RESULTS Among 102 patients, complications developed in 24 (23%). Complications developed in only 8% of patients with Ranson score <2, making routine early CT unnecessary. For the patients with Ranson score <2 and Balthazar grades A and B at day 1 CT, late CT seemed to be useless. Complication was suspected by clinical and biologic tests before day 7 in 22 of 24 complicated patients (92%), suggesting that CT could be proposed only in cases of clinical or biologic deterioration. Late CT was correlated with a complicated course in patients with Balthazar grades D and E or intrapancreatic necrosis >50%. Late CT was predictive of complications in cases of intrapancreatic necrosis enlarging since the first examination. CONCLUSIONS Our study showed that in acute pancreatitis: 1) there is little justification for systematic early CT, especially in patients with Ranson score <2, and 2) late CT does not need to be performed routinely, but only in cases of clinical or biologic worsening.

Diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock.

BACKGROUND Emphasis in therapy of human septic shock is shifting towards reliable end points and predictors of survival. Rationale is to study whether the evolution of cardiovascular reactivity in view of the administered doses of norepinephrine is an early predictor of in-hospital survival and to determine the optimal threshold of norepinephrine therapy and its consequences on renal function. METHODS Observational study of a prospective cohort of patients in septic shock, hospitalized in intensive care unit at least 24 hours before requiring norepinephrine. Excluded were patients requiring <72 hours of continuous norepinephrine (16 patients) or who received corticosteroids. Hemodynamic parameters (heart rate, blood pressure, urinary output, and temperature) were continuously monitored. RESULTS Of 68 patients, 45 survived [intensive care unit stay of 24 (12-36) days, hospital stay of 36 (27-66) days], and 23 died 5 (3-10) days after septic shock onset and norepinephrine treatment. Multivariate analysis revealed four independent positive predictive factors of short-term (10 days) outcome: Simplified Acute Physiology Score (SAPS) II <50 [odds ratio (OR) 6.4, 95% confidence interval (95% CI) 1.3-30.7, p < 0.011], and on day 3 Logistic Organ Dysfunction System (LODS) score <6 (OR 29.1, 95% CI 2.7-314.3, p = 0.0056), norepinephrine concentration <0.5 mug/kg/min (OR 17.6, 95% CI 2.2-142.0, p < 0.0007), diastolic arterial pressure >50 mm Hg (OR 24.8, 95% CI 2.9-215.9, p < 0.004), but not systolic arterial pressure. CONCLUSIONS Septic shock survival increases when dose of 0.5 mug/kg/min of norepinephrine continuously improves vascular tone within the first 48 hours, or when diastolic arterial pressure (>50 mm Hg) is restored. Norepinephrine has beneficial effects on renal function. Predictive value of LODS score on day 3 is demonstrated, while SAPS II is confirmed as the only reliable predictive factor in first 24 hours.

Local and systemic innate immune response to secondary human peritonitis.

IntroductionOur aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology.MethodsPeritoneal and plasma cytokines (interleukin (IL) 1, tumor necrosis factor α (TNFα), IL-6, IL-10, and interferon γ (IFNγ)) were measured in 66 patients with secondary peritonitis.ResultsThe concentration ratio between peritoneal fluid and plasma cytokines varied from 5 (2 to 21) (IFNγ) to 1310 (145 to 3888) (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFα, IL-6, IFNγ and IL-10 were higher in patients with shock versus no shock and in nonsurvivors versus survivors (P ≤0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. The presence of anaerobes or Enterococcus species in peritoneal fluid was associated with higher plasma TNFα: 50 (37 to 106) versus 38 (29 to 66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes and Enterococcus species was associated with higher peritoneal IFNγ: 2 (1 to 6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05, respectively).ConclusionsPeritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Higher levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non-survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis.

Protracted immune disorders at one year after ICU discharge in patients with septic shock

BackgroundSepsis is a leading cause of mortality and critical illness worldwide and is associated with an increased mortality rate in the months following hospital discharge. The occurrence of persistent or new organ dysfunction(s) after septic shock raises questions about the mechanisms involved in the post-sepsis status. The present study aimed to explore the immune profiles of patients one year after being discharged from the intensive care unit (ICU) following treatment for abdominal septic shock.MethodsWe conducted a prospective, single-center, observational study in the surgical ICU of a university hospital. Eighty-six consecutive patients admitted for septic shock of abdominal origin were included in this study. Fifteen different plasma biomarkers were measured at ICU admission, at ICU discharge and at one year after ICU discharge. Three different clusters of biomarkers were distinguished according to their functions, namely: (1) inflammatory response, (2) cell damage and apoptosis, (3) immunosuppression and resolution of inflammation. The primary objective was to characterize variations in the immune status of septic shock patients admitted to ICU up to one year after ICU discharge. The secondary objective was to evaluate the relationship between these biomarker variations and patient outcomes.ResultsAt the onset of septic shock, we observed a cohesive pro-inflammatory profile and low levels of inflammation resolution markers. At ICU discharge, the immune status demonstrated decreased but persistent inflammation and increased immunosuppression, with elevated programmed cell death protein-1 (PD-1) levels, and a counterbalanced resolution process, with elevated levels of interleukin-10 (IL-10), resolvin D5 (RvD5), and IL-7. One year after hospital discharge, homeostasis was not completely restored with several markers of inflammation remaining elevated. Remarkably, IL-7 was persistently elevated, with levels comparable to those observed after ICU discharge, and PD-1, while lower, remained in the elevated abnormal range.ConclusionsIn this study, protracted immune disturbances were observed one year after ICU discharge. The study results suggested the presence of long-lasting immune illness disorders following a long-term septic insult, indicating the need for long-term patient follow up after ICU discharge and questioning the use of immune intervention to restore immune homeostasis after abdominal septic shock.