Local and systemic innate immune response to secondary human peritonitis.

INTRODUCTION: Our 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. METHODS: Peritoneal 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. RESULTS: The 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). CONCLUSIONS: Peritonitis 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.

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

INTRODUCTION: The 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. METHODS: This 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). RESULTS: Frequency 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. CONCLUSIONS: Unlike 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.

Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Attempts to reverse cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) rely on a limited number of treatments. Calcium channel blockers have proven a benefit but their vasodilating effect on spastic cerebral arteries is relatively modest. Milrinone, a phosphodiesterase inhibitor, combines vasodilating and inotropic properties, but limited data exist to support its use for the treatment of CVS. We assessed the efficacy and tolerance of milrinone in patients with CVS secondary to aSAH. METHODS: Twenty-two consecutive patients with angiographically-proven CVS (arterial diameter reduction >40%) have been studied. Intraarterial milrinone was infused in the cerebral territory(ies) involved and followed by continuous intravenous infusion until Day 14 after initial bleeding. We evaluated angiographic reversal of CVS, hemodynamic tolerance, and neurological outcome 1 year after aSAH. RESULTS: Thirty-four selective intraarterial infusions of milrinone were required to treat 72 vasospastic territories. Intraarterial milrinone resulted in 53+/-37% increase in arterial diameter (P<.0001). Milrinone infusion resulted in moderately increased heart rate, but systemic arterial pressure remained unchanged. Five patients (23%) had angiographically-proven vasospasm recurrence within 48 hours after the procedure. Two of them were successfully reversed after another intraarterial infusion of milrinone. The remaining 3 underwent mechanical angioplasty. Two patients (9%) died in ICU, and 2 were lost to follow-up. All other patients had very good neurological outcome (modified Rankin scale: 0.8+/-1.0; Barthel index: 100 [95-100]). CONCLUSIONS: This study suggests that milrinone is effective and safe for reversal of CVS after aSAH and should be tested in a large randomized trial.

Adrenal response in patients with septic shock of abdominal origin: relationship to survival.

OBJECTIVE: To evaluate the prognostic value of adrenocortical response to corticotropin in septic shock patients operated on exclusively for an intra-abdominal source of infection. DESIGN AND SETTING: Prospective, observational, single-center study in a surgical intensive care unit of a university hospital PATIENTS: 118 consecutive septic shock patients undergoing laparotomy or drainage for intra-abdominal infection. MEASUREMENTS AND RESULTS: Baseline cortisol (t (0)) and cortisol response to corticotropin test (Delta) were measured during the first 24 h following onset of shock. The relationship between adrenal function test results and survival was analyzed as well as the effect of etomidate anesthesia. Cortisol plasma level at t (0) was higher in nonsurvivors than in survivors (33 +/- 23 vs. 25 +/- 14 microg/dl), but the response to corticotropin test did not differ between these two subgroups. ROC analysis showed threshold values for t (0) (32 microg/dl) and Delta (8 microg/dl) that best discriminated survivors from nonsurvivors in our population. We observed no difference in survival at the end of hospital stay using log rank test when patients were separated according to t (0), Delta, or both. In addition, adrenal function tests and survival did not differ in patients who received etomidate anesthesia (n = 69) during the surgical treatment of their abdominal sepsis. CONCLUSIONS: In this cohort of patients with abdominal septic shock baseline cortisol level and the response to corticotropin test did not discriminate survivors from nonsurvivors. No deleterious impact of etomidate anesthesia on adrenal function tests and survival was observed in these patients.

Inflammatory cytokines, C reactive protein, and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis.

BACKGROUND: Infection of necrosis is a major risk factor in patients with acute pancreatitis. Systematic use of broad spectrum antibiotics has been recommended in these patients but may induce serious side effects. To better target patients in whom antibiotic prophylaxis could be beneficial, we evaluated whether early serum profiles of interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha, C reactive protein (CRP) and procalcitonin (PCT) help to discriminate between patients who eventually develop infection of necrosis and those who do not. METHODS: Forty-eight patients with acute pancreatitis and a computed tomography (CT) severity index score of more than 3 were prospectively screened. They were then separated into infected and non-infected groups according to the occurrence of infected pancreatic necrosis. The severity of illness was assessed with Ranson's classification and Simplified Acute Physiologic Score II. Serum levels of IL-6, TNF-alpha, CRP, and PCT were measured during the first 3 days after admission. CT-guided fine needle aspiration of pancreatic necrosis was performed to prove infection when sepsis of abdominal origin was suspected. Using the methodology of receiver operating curves, we determined the presence of a threshold for markers that would be predictive of the development of infected necrosis. RESULTS: PCT and IL-6 were higher in the serum of patients who eventually developed infection of necrosis (P < 0.003 and < 0.04, respectively). No difference was noted between the 2 groups for TNF- alpha and CRP. The combination of IL-6 < 400 pg/l and PCT < 2 ng/L best identified patients who were not at risk for necrosis infection. The negative predictive value for these thresholds was 91%, whereas sensitivity and specificity were 75% and 84%. CONCLUSIONS: PCT and IL-6 serum levels were elevated very early in patients who eventually developed necrosis infection. A combination of PCT and IL-6 thresholds could be helpful in identifying a subgroup of patients in whom antibiotic prophylaxis is likely to be ineffective.

Redistribution of cardiac output during hemorrhagic shock in sheep.

OBJECTIVE: Our goal was to evaluate the robustness of one of the assumptions used by esophageal Doppler monitors to compute systemic stroke volume and cardiac output; i.e., a constant flow proportion between supra-aortic vessels and descending aorta. For this purpose, we measured ascending and descending aortic blood flows during acute hemorrhage in anesthetized ewes. DESIGN: Prospective, experimental study. SETTING: Animal research facility. SUBJECTS: Adult ewes. INTERVENTIONS: Anesthetized animals were implemented with an aortic pressure transducer and two ultrasound transit time flowmeters placed around ascending and descending aorta, respectively. After baseline measurements, three incremental blood withdrawals were followed by progressive blood restitution in three similar steps. MEASUREMENTS AND MAIN RESULTS: Ascending and descending aortic blood flows were reduced in a proportional manner after hemorrhage (-48% and -46%, respectively; p < .05 vs. baseline). Following blood restitution, flows were not fully restored, but ascending aortic flow was reduced by 27% with respect to initial control values while descending aortic flow was only 15% below. The agreement between ascending aortic flow and cardiac output calculated as descending aortic flow divided by 0.7 was characterized by a bias of 0.07 L/min and limits of agreement of +1.24 L/min and -1.10 L/min. CONCLUSIONS: Minor blood flow redistribution between supra-aortic and descending aortic territories was seen only following blood restitution but not during hemorrhage in these anesthetized ewes. This observation supports the robustness of the assumption of constant flow proportion used by the esophageal Doppler monitor to calculate systemic stroke volume from descending aortic flow measurements.

Noninvasive techniques for measurements of cardiac output.

PURPOSE OF REVIEW: Measuring stroke volume or cardiac output is of paramount importance for the management of critically ill patients in the intensive care unit, or 'high risk' surgical patients in the operating room. The new noninvasive techniques are gaining acceptance among intensivists and anesthesiologists who have been trained almost exclusively in the pulmonary artery catheter and the thermodilution technique. RECENT FINDINGS: The present review focuses on the recent publications related to esophageal Doppler, Fick principle applied to carbon dioxide associated with partial rebreathing, and pulse contour analysis. Recent validation studies have confirmed the previous findings: all three methods provide reliable estimations of cardiac output and its variations. There is not a single method standing out and ruling out the others. Many investigators are now using one of the 'noninvasive' monitors to measure cardiac output in clinical or experimental studies. SUMMARY: By making cardiac output easily measurable in various settings, these techniques should all contribute to improve hemodynamic management in critically ill or high-risk surgical patients.

Esophageal Doppler: noninvasive cardiac output monitor.

In this article we describe the esophageal Doppler, a noninvasive, instantaneous cardiac output monitor. Its reliability has been demonstrated to be comparable to that of other current techniques used in the clinical arena to measure cardiac output. It helps guiding intravascular fluid resuscitation by quantifying the increase in flow in response to fluid challenges and by indicating the plateau of the patient's cardiac function curve. When the plateau has been reached, further fluid loading may result in congestion without improvement in systemic flow. Thus, measuring cardiac output is the only way to determine the upper limit for fluid intake. In addition, a strategy based on cardiac output optimization has proven beneficial in high-risk surgical patients.

Detection of lung cancer on radiographs: receiver operating characteristic analyses of radiologists', pulmonologists', and anesthesiologists' performance.

PURPOSE: To compare and quantify, by means of receiver operating characteristic (ROC) and localization ROC analyses, the performance of radiologists, pulmonologists, and anesthesiologists (residents and staff) in the detection of missed lung cancer. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was not required or obtained for review of radiographs. A set of 60 posteroanterior chest radiographs was presented to 36 observers: 12 radiologists, 12 pulmonologists, and 12 anesthesiologists. Each of these three observer categories included six residents and six staff. Thirty of the radiographs each depicted one lung cancer that was overlooked at prospective image interpretation; the other 30 were normal radiographs matched for age and smoking history. Observers were asked to rate their degree of suspicion concerning the presence of lung cancer by using a visual analog scale and to point out the zone of suspicion on a schematic of the lung. These data were used to generate combined ROC-localization ROC curves and to assess performance. Intraobserver consistency was evaluated by using intraclass correlation coefficients and weighted kappa statistics. RESULTS: Areas under the ROC curves indicated better performance for radiologists and pulmonologists compared with anesthesiologists (P < .002) and for staff compared with residents (P < .022). Performance was lower for all categories of observers when localization ROC curves were used. Radiologists and staff pulmonologists showed a higher degree of confidence in the assessment of normality than did other categories of physicians. Intraobserver consistency was poor. CONCLUSION: Experienced readers showed better ability to distinguish normality from abnormality. Combined ROC and localization ROC analyses gave a more reliable quantification of observer performance than did ROC analysis alone.

Increasing maternal blood pressure with ephedrine increases uterine artery blood flow velocity during uterine contraction.

BACKGROUND: During labor, ephedrine is widely used to prevent or to treat maternal arterial hypotension and restore uterine perfusion pressure to avoid intrapartum fetal asphyxia. However, the effects of ephedrine on uterine blood flow have not been studied during uterine contractions. The purpose of the study was to assess the effects of ephedrine on uterine artery velocities and resistance index using the Doppler technique during the active phase of labor. METHODS: Ten normotensive, healthy parturients with uncomplicated pregnancies at term received intravenous ephedrine during labor to increase mean arterial pressure up to a maximum of 20% above their baseline pressure. Peak systolic and end-diastolic Doppler flow velocities and resistance indices were measured in the uterine artery before and immediately after administration of bolus intravenous ephedrine and after ephedrine washout. Umbilical and fetal middle cerebral arterial resistance indices and fetal heart rate were also calculated. RESULTS: After ephedrine administration, mean arterial pressure increased by 17 +/- 4%. End-diastolic flow velocity in the uterine artery at peak amplitude of uterine contraction was restored to 74% of the value observed in the absence of contraction. The systolic velocity was totally restored, and the uterine resistance index was significantly decreased, compared with the values in the absence of contraction. Between uterine contractions, ephedrine induced similar but less marked effects. Fetal hemodynamic parameters were not altered by ephedrine administration. CONCLUSIONS: Bolus administration of intravenous ephedrine reversed the dramatic decrease in diastolic uteroplacental blood flow velocity and the increase in resistance index during uterine contraction, without altering fetal hemodynamic parameters. This suggests that the increase in uterine perfusion pressure during labor could in part restore uterine blood flow to the placenta during uterine contraction.